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<title>Abstract</title>
Radon inhalation activates antioxidative functions in mouse organs, thereby contributing to inhibition of oxidative stress-induced damage. However, the specific redox state of each organ after radon inhalation has not been reported. Therefore, in this study, we evaluated the redox state of various organs in mice following radon inhalation at concentrations of 2 or 20 kBq/m3 for 1, 3 or 10 days. Scatter plots were used to evaluate the relationship between antioxidative function and oxidative stress by principal component analysis (PCA) of data from control mice subjected to sham inhalation. The results of principal component (PC) 1 showed that the liver and kidney had high antioxidant capacity; the results of PC2 showed that the brain, pancreas and stomach had low antioxidant capacities and low lipid peroxide (LPO) content, whereas the lungs, heart, small intestine and large intestine had high LPO content but low antioxidant capacities. Furthermore, using the PCA of each obtained cluster, we observed altered correlation coefficients related to glutathione, hydrogen peroxide and LPO for all groups following radon inhalation. Correlation coefficients related to superoxide dismutase in organs with a low antioxidant capacity were also changed. These findings suggested that radon inhalation could alter the redox state in organs; however, its characteristics were dependent on the total antioxidant capacity of the organs as well as the radon concentration and inhalation time. The insights obtained from this study could be useful for developing therapeutic strategies targeting individual organs.

DOI： 10.1093/jrr/rraa129

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Radon therapy has been traditionally performed globally for oxidative stress-related diseases. Many researchers have studied the beneficial effects of radon exposure in living organisms. However, the effects of thoron, a radioisotope of radon, have not been fully examined. In this study, we aimed to compare the biological effects of radon and thoron inhalation on mouse organs with a focus on oxidative stress. Male BALB/c mice were randomly divided into 15 groups: sham inhalation, radon inhalation at a dose of 500 Bq/m3 or 2000 Bq/m3, and thoron inhalation at a dose of 500 Bq/m3 or 2000 Bq/m3 were carried out. Immediately after inhalation, mouse tissues were excised for biochemical assays. The results showed a significant increase in superoxide dismutase and total glutathione, and a significant decrease in lipid peroxide following thoron inhalation under several conditions. Additionally, similar effects were observed for different doses and inhalation times between radon and thoron. Our results suggest that thoron inhalation also exerts antioxidative effects against oxidative stress in organs. However, the inhalation conditions should be carefully analyzed because of the differences in physical characteristics between radon and thoron.

DOI： 10.1007/s00411-020-00843-0

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<title>Abstract</title>
The forced swim test (FST) is a screening model for antidepressant activity; it causes immobility and induces oxidative stress. We previously reported that radon inhalation has antidepressant-like effects in mice potentially through the activation of antioxidative functions upon radon inhalation. This study aimed to investigate the effect of prior and post low-dose X-irradiation (0.1, 0.5, 1.0 and 2.0 Gy) on FST-induced immobility and oxidative stress in the mouse brain, and the differences, if any, between the two. Mice received X-irradiation before or after the FST repeatedly for 5 days. In the post-FST-irradiated group, an additional FST was conducted 4 h after the last irradiation. Consequently, animals receiving prior X-irradiation (0.1 Gy) had better mobility outcomes than sham-irradiated mice; however, their levels of lipid peroxide (LPO), an oxidative stress marker, remained unchanged. However, animals that received post-FST X-irradiation (0.5 Gy) had better mobility outcomes and their LPO levels were significantly lower than those of the sham-irradiated mice. The present results indicate that 0.5 Gy X-irradiation after FST inhibits FST-induced immobility and oxidative stress in mice.

DOI： 10.1093/jrr/rraa022

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Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：ZOOLOGICAL SOC PAKISTAN  

Cisplatin (CDDP) is widely used for treating solid cancers; however, it induces nephrotoxicity caused by oxidative stress. Here, we investigated whether radon inhalation has different effects against CDDP-induced renal injury in two mouse strains differing in radiosensitivity, and determined the appropriate dose of CDDP combined with radon inhalation for highly radiosensitive mice. CDDP was administered at 20 mg/kg weight to C57BL/6J and BALB/c mice after radon inhalation at 1000 Bq/m(3) and 2000 Bq/m(3) for 24 h. Radon inhalation had a slight positive effect against CDDP toxicity in C57BL/6J mice with respect to improved hair condition, whereas radon inhalation exacerbated CDDP-induced toxicity in BALB/c mice, such as a decrease in hair condition, higher creatinine levels, and decreased antioxidant contents (catalase and glutathione). When BALB/c mice were treated with a lower dose of CDDP (15 mg/kg) after 1000 Bq/m(3) radon inhalation, the creatinine level was reduced and the superoxide dismutase content was increased, suggesting that this combination might have a protective effect against the CDDP-induced renal damage. The supportive effect of radon inhalation shows its good potential as a candidate treatment to alleviate CDDP-induced renal damage in veterinary medicine.

DOI： 10.17582/journal.pjz/2018.50.3.1157.1170

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<title>Abstract</title>
Although radon inhalation increases superoxide dismutase (SOD) activities in mouse organs, the mechanisms and pathways have not yet been fully clarified. The aim of this study was to determine the details of SOD activation in mouse brain tissue following the inhalation of radon at concentrations of 500 or 2000 Bq/m3 for 24 h. After inhalation, brains were removed quickly for analysis. Radon inhalation increased the manganese (Mn)-SOD level and mitochondrial SOD activity. However, the differences were not significant. There were no changes in the Cu/Zn-SOD level or cytosolic SOD activity. Radon inhalation increased the brain nuclear factor (NF)-κB content, which regulates the induction of Mn-SOD, in the nuclear and cytosolic compartments. The level of inhibitor of nuclear factor κB kinase subunit β (IKK-β), which activates NF-κB, was slightly increased by radon inhalation. The expression of cytoplasmic ataxia-telangiectasia mutated kinase in mice inhaling radon at 500 Bq/m3 was 50% higher than in control mice. In addition, NF-κB–inducing kinase was slightly increased after inhaling radon at 2000 Bq/m3. These findings suggest that radon inhalation might induce Mn-SOD protein via NF-κB activation that occurs in response to DNA damage and oxidative stress.

DOI： 10.1093/jrr/rrx048

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Radon therapy using radon (Rn-222) gas is classified into two types of treatment: inhalation of radon gas and drinking water containing radon. Although short- or long-term intake of spa water is effective in increasing gastric mucosal blood flow, and spa water therapy is useful for treating chronic gastritis and gastric ulcer, the underlying mechanisms for and precise effects of radon protection against mucosal injury are unclear. In the present study, we examined the protective effects of hot spring water drinking and radon inhalation on ethanol-induced gastric mucosal injury in mice. Mice inhaled radon at a concentration of 2000 Bq/m(3) for 24 h or were provided with hot spring water for 2 weeks. The activity density of Rn-222 ranged from 663 Bq/l (start point of supplying) to 100 Bq/l (end point of supplying). Mice were then orally administered ethanol at three concentrations. The ulcer index (UI), an indicator of mucosal injury, increased in response to the administration of ethanol; however, treatment with either radon inhalation or hot spring water inhibited the elevation in the UI due to ethanol. Although no significant differences in antioxidative enzymes were observed between the radon-treated groups and the non-treated control groups, lipid peroxide levels were significantly lower in the stomachs of mice pre-treated with radon or hot spring water. These results suggest that hot spring water drinking and radon inhalation inhibit ethanol-induced gastric mucosal injury.

DOI： 10.1093/jrr/rrx021

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<title>Abstract</title>
In our previous studies, we found that low-dose radiation inhibits oxidative stress–induced diseases due to increased antioxidants. Although these effects of low-dose radiation were demonstrated, further research was needed to clarify the effects. However, the analysis of oxidative stress is challenging, especially that of low levels of oxidative stress, because antioxidative substances are intricately involved. Thus, we proposed an approach for analysing oxidative liver damage via use of a self-organizing map (SOM)—a novel and comprehensive technique for evaluating hepatic and antioxidative function. Mice were treated with radon inhalation, irradiated with X-rays, or subjected to intraperitoneal injection of alcohol. We evaluated the oxidative damage levels in the liver from the SOM results for hepatic function and antioxidative substances. The results showed that the effects of low-dose irradiation (radon inhalation at a concentration of up to 2000 Bq/m3, or X-irradiation at a dose of up to 2.0 Gy) were comparable with the effect of alcohol administration at 0.5 g/kg bodyweight. Analysis using the SOM to discriminate small changes was made possible by its ability to ‘learn’ to adapt to unexpected changes. Moreover, when using a spherical SOM, the method comprehensively examined liver damage by radon, X-ray, and alcohol. We found that the types of liver damage caused by radon, X-rays, and alcohol have different characteristics. Therefore, our approaches would be useful as a method for evaluating oxidative liver damage caused by radon, X-rays and alcohol.

DOI： 10.1093/jrr/rrw083

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In this study, we compared the protective effects of radon inhalation and ascorbic acid administration on transient global cerebral ischemic injury in gerbils. Gerbils were treated with radon inhalation (2000 Bq/m(3), 24 hours) or ascorbic acid (100, 300, or 500mg/kg body weight). Then, transient global cerebral ischemia was induced by bilateral occlusion of the common carotid artery. Results showed that the number of damaged neurons was significantly increased in gerbils that underwent ischemia compared with that in control gerbils. However, the number of damaged neurons in gerbils treated with radon or 500mg/kg of ascorbic acid before ischemia was significantly lower than gerbils who were subjected to ischemia without any pretreatment, and the protective effects of radon inhalation were similar to the effects of administering 500mg/kg ascorbic acid. The levels of superoxide dismutase (SOD) and total glutathione (t-GSH) in brain tissue were increased to a similar extent by pretreatment with radon inhalation or 500mg/kg of ascorbic acid. These findings suggested that radon inhalation has a protective antioxidative effect against transient global cerebral ischemic injury similar to 500mg/kg ascorbic acid treatment.

DOI： 10.1080/00223131.2016.1198731

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In this study, we investigated the suppressive effects of radon inhalation against nephropathy in C57BL/6J mice with type-1 diabetes induced by intraperitoneal injection of streptozotocin (50 mg/kg weight, given five times). Four weeks after diabetes induction, the diabetic mice were continuously treated with inhaled radon-222 of 2000 Bq/m(3) or air only (sham) for four weeks. The results showed that radon inhalation did not affect type-1 diabetic symptoms such as body weight loss, hyperglycemia, and hypoinsulinemia. However, diabetic mice treated with radon showed lower urinary albumin excretion and fibrotic change in renal glomeruli compared with diabetic mice not treated with radon. Furthermore, renal superoxide dismutase activity and glutathione content were significantly higher in diabetic mice treated with radon than in diabetic mice not treated with radon. These findings suggested that radon inhalation enhanced renal antioxidants activities, resulting in the suppression of diabetic nephropathy. This study may contribute to the development of a novel approach in the treatment of nephropathy for diabetic patients.

DOI： 10.1080/00223131.2015.1078751

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Although radon therapy is indicated for hyperuricemia, the underlying mechanisms of action have not yet been elucidated in detail. Therefore, we herein examined the inhibitory effects of radon inhalation and hot spring water drinking on potassium oxonate (PO)-induced hyperuricemia in mice. Mice inhaled radon at a concentration of 2000 Bq/m(3) for 24 h or were given hot spring water for 2 weeks. Mice were then administrated PO at a dose of 500 mg/kg. The results obtained showed that serum uric acid levels were significantly increased by the administration of PO. Radon inhalation or hot spring water drinking significantly inhibited elevations in serum uric acid levels through the suppression of xanthine oxidase activity in the liver. Radon inhalation activated anti-oxidative functions in the liver and kidney. These results suggest that radon inhalation inhibits PO-induced hyperuricemia by activating anti-oxidative functions, while hot spring water drinking may suppress PO-induced elevations in serum uric acid levels through the pharmacological effects of the chemical compositions dissolved in it.

DOI： 10.1093/jrr/rrw014

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Radon inhalation brings pain relief for chronic constriction injury- (CCI-) induced neuropathic pain in mice due to the activation of antioxidative functions, which is different from the mechanism of the pregabalin effect. In this study, we assessed whether a combination of radon inhalation and pregabalin administration is more effective against neuropathic pain than radon or pregabalin only. Mice were treated with inhaled radon at a concentration of 1,000 Bq/m(3) for 24 hours and pregabalin administration after CCI surgery. In mice treated with pregabalin at a dose of 3 mg/kg weight, the 50% paw withdrawal threshold of mice treated with pregabalin or radon and pregabalin was significantly increased, suggesting pain relief. The therapeutic effects of radon inhalation or the combined effects of radon and pregabalin (3 mg/kg weight) were almost equivalent to treatment with pregabalin at a dose of 1.4 mg/kg weight or 4.1 mg/kg weight, respectively. Radon inhalation and the combination of radon and pregabalin increased antioxidant associated substances in the paw. The antioxidant substances increased much more in radon inhalation than in pregabalin administration. These findings suggested that the activation of antioxidative functions by radon inhalation enhances the pain relief of pregabalin and that this combined effect is probably an additive effect.

DOI： 10.1155/2016/9853692

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It has been reported that radon inhalation activates antioxidative functions in liver and has an antioxidative effect against hepatopathy similar to that of the antioxidative effects of ascorbic acid (VC) or -tocopherol (VE). In this study, we examined the combined effects of radon inhalation and antioxidant vitamin administration on acute alcohol-induced hepatopathy in mice. ICR mice were subjected to intraperitoneal (i.p.) administration of alcohol after pretreating with air only (sham) or radon at a concentration of approximately 2000 Bq/m(3) for 24 hours and i.p. administration of VC (300 mg/kg body weight) or VE (300 mg/kg body weight). In mice injected with alcohol, the combined radon and antioxidant vitamins treatment significantly decreased the activities of glutamic oxaloacetic transaminase in serum compared to not only the alcohol-administered group (sham group), but also the radon inhalation with alcohol administration group or the vitamin and alcohol administration group. In addition, radon inhalation significantly increased the antioxidant level, in such as the catalase activity and the total glutathione content in liver compared to the sham group. These results suggested that the combined radon and antioxidant vitamin treatment could effectively inhibit alcohol-induced hepatopathy in mice without any antagonizing action.

DOI： 10.1080/00223131.2015.1014875

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DOI： 10.14800/ics.601

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Although brain disorders are not the main indication for radon therapy, our previous study suggested that radon inhalation therapy might mitigate brain disorders. In this study, we assessed whether radon inhalation protects against transient global cerebral ischemic injury in gerbils. Gerbils were treated with inhaled radon at a concentration of 2,000 Bq/m(3) for 24 h. After radon inhalation, transient global cerebral ischemia was induced by bilateral occlusion of the common carotid artery. Results showed that transient global cerebral ischemia induced neuronal damage in hippocampal CA1, and the number of damaged neurons was significantly increased compared with control. However, radon treatment inhibited ischemic damage. Superoxide dismutase (SOD) activity in the radon-treated gerbil brain was significantly higher than that in sham-operated gerbils. These findings suggested that radon inhalation activates antioxidative function, especially SOD, thereby inhibiting transient global cerebral ischemic injury in gerbils.

DOI： 10.1007/s10753-014-9896-z

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DOI： 10.4172/2168-9652.1000133

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Background Radon therapy is clinically useful for the treatment of pain-related diseases. However, there have been no studies regarding the effects of radon inhalation on neuropathic pain. In this study, we aimed to determine whether radon inhalation actually induced a remission of neuropathic pain and improved the quality of life. Methods First, we investigated the antinociceptive effects of radon inhalation in the chronic constriction injury (CCI) model of neuropathic pain. We evaluated pain behaviour in mice before and after CCI surgery, using von Frey test. Pretreated mice received CCI surgery immediately after 24-h inhalation of radon at background (BG) concentration (c. 19Bq/m3), or at a concentration of 1000 or 2000Bq/m3, and post-treated mice inhaled similar levels of radon 2 days after CCI surgery. Results CCI surgery induced mechanical allodynia and hyperalgesia on a plantar surface of mice, as assessed using von Frey test, and 2000Bq/m3 radon inhalation alleviated hyperalgesic conditions 2237% compared to BG level concentration. Concurrently, CCI surgery increased norepinephrine (NE), tumour necrosis factor-alpha (TNF-) and nitric oxide (NO) concentrations in plasma, and leukocyte migration in paws. Furthermore, CCI-induced neuropathy reduced superoxide dismutase (SOD) activity. Treatment with radon inhalation, specifically at a concentration of 2000Bq/m3, produced antinociceptive effects, i.e., lowered plasma TNF-, NE and NO levels and restored SOD activity, as well as pain-related behaviour. Conclusions This study showed that inhalation of 2000Bq/m3 radon prevented and alleviated CCI-induced neuropathic pain in mice.

DOI： 10.1002/j.1532-2149.2012.00210.x

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Radon therapy is clinically useful for the treatment of inflammatory diseases. The mechanisms of pain relief remain to be fully elucidated. In this study, we investigated the antinociceptive effects of radon inhalation in a mouse model of formalin-induced inflammatory pain. Immediately, after radon inhalation at a concentration of background level (ca. 19 Bq/m(3)), 1,000 or 2,000 Bq/m(3) for 24 h, 1.35 % formalin (0.5 % formaldehyde in saline, 20 mu l) was subcutaneously injected into the hind paw of mice, and we measured licking response time. Radon inhalation inhibited the second phase of response in formalin test. Formalin administration induced nociception and increased tumor necrosis factor alpha (TNF-alpha) and nitric oxide (NO) levels in serum and leukocyte migration in paws. Concurrently, formalin injection decreased antioxidative functions. Radon inhalation produced antinociceptive effects, i.e., lowered serum TNF-alpha and NO levels, and restored antioxidative functions. The results showed that radon inhalation inhibited formalin-induced inflammatory pain.

DOI： 10.1007/s10753-012-9554-2

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We examined the protective effect of radon inhalation on streptozotocin (STZ)-induced type-1 diabetes in mice. Mice inhaled radon at concentrations of 1000, 2500, and 5500 Bq/m3 for 24 hours before STZ administration. STZ administration induced characteristics of type-1 diabetes such as hyperglycemia and hypoinsulinemia
however, radon inhalation at doses of 1000 and 5500 Bq/m3 significantly suppressed the elevation of blood glucose in diabetic mice. Serum insulin was significantly higher in mice pre-treated with radon at a dose of 1000 Bq/m3 than in mice treated with a sham. In addition, superoxide dismutase activities and total glutathione contents were significantly higher and lipid peroxide was significantly lower in mice pre-treated with radon at doses of 1000 and 5500 Bq/m3 than in mice treated with a sham. These results were consistent with the result that radon inhalation at 1000 and 5500 Bq/m3 suppressed hyperglycemia. These findings suggested that radon inhalation suppressed STZ-induced type-1 diabetes through the enhancement of antioxidative functions in the pancreas. © 2013 Institute of Physiology v.v.i., Academy of Sciences of the Czech Republic, Prague, Czech Republic.

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We have previously reported that radon inhalation activates anti-oxidative functions and inhibits carbon tetrachloride (CCl4)-induced hepatopathy. It has also been reported that antioxidant vitamins can inhibit CCl4-induced hepatopathy. In the current study, we examined the comparative efficacy of treatment with radon, ascorbic acid and alpha-tocopherol on CCl4-induced hepatopathy. Mice were subjected to intraperitoneal injection of CCl4 after inhaling approximately 1000 or 2000 Bq/m(3) radon for 24 h, or immediately after intraperitoneal injection of ascorbic acid (100, 300, or 500 mg/kg bodyweight) or alpha-tocopherol (100, 300, or 500 mg/kg bodyweight). We estimated the inhibitory effects on CCl4-induced hepatopathy based on hepatic function-associated parameters, oxidative damage-associated parameters and histological changes. The results revealed that the therapeutic effects of radon inhalation were almost equivalent to treatment with ascorbic acid at a dose of 500 mg/kg or alpha-tocopherol at a dose of 300 mg/kg. The activities of superoxide dismutase, catalase, and glutathione peroxidase in the liver were significantly higher in mice exposed to radon than in mice treated with CCl4 alone. These findings suggest that radon inhalation has an anti-oxidative effect against CCl4-induced hepatopathy similar to the anti-oxidative effects of ascorbic acid or alpha-tocopherol due to the induction of anti-oxidative functions.

DOI： 10.1093/jrr/rrs057

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Since the 2011 nuclear accident in Fukushima, the effects of low-dose irradiation, especially internal exposure, are at the forefront of everyone's attention. However, low-dose radiation induced various stimulating effects such as activation of antioxidative and immune functions. In this study, we attempted to evaluate the quantitative effects of the activation of antioxidative activities in kidney induced by radon inhalation on carbon tetrachloride (CCl4)-induced renal damage. Mice were subjected to intraperitoneal (i.p.) injection of CCl4 after inhaling approximately 1000 or 2000 Bq/m(3) radon for 24 h, or immediately after i.p. injection of alpha-tocopherol (100, 300, or 500 mg/kg bodyweight). In case of renal function, radon inhalation at a concentration of 2000 Bq/m(3) has the inhibitory effects similar to alpha-tocopherol treatment at a dose of 300-500 mg/kg bodyweight. The activities of superoxide dismutase and catalase in kidneys were significantly higher in mice exposed to radon as compared to mice treated with CCl4 alone. These findings suggest that radon inhalation has an antioxidative effect against CCl4-induced renal damage similar to the antioxidative effects of alpha-tocopherol due to induction of antioxidative functions.

DOI： 10.3109/0886022X.2012.717496

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It is well known that cigarette tobaccos contain naturally occurring radioactive nuclides such as Pb-210 and Po-210. In many countries, the radioactivity of tobaccos has been measured to estimate the effective dose from smoking inhalation. The present study covered 24 cigarette brands including the top 20 of sales in Japan between April 2008 and March 2009. The activity concentrations of Pb-210 were measured by gamma-ray spectrometry, and then those of its progeny (Po-210) were evaluated assuming the radioactive equilibrium between the two nuclides. Their concentrations were in the range of 214 mBq cigarette(1) with an arithmetic mean of 83 mBq cigarette(1). The annual committed effective doses were also calculated, based on the scenario that a smoker consumes 20 cigarettes a day. The average doses from Pb-210 and Po-210 inhalations were 229 and 6827 Sv y(1), respectively.

DOI： 10.1093/rpd/ncr364

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Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：IJRR-IRANIAN JOURNAL RADIATION RES  

Background: The aim of this study was to analyze the effects of thoron and thermal treatment for aging-related diseases in humans. Materials and Methods: All subjects inhaled thoron with a high concentration (about 4900 Bq/m(3)) for 2 weeks. Blood pressures were measured and blood samples were collected after each treatment 1, 2 and 3 weeks after the first treatment. Results: The alpha-atrial natriuretic peptide level of the rheumatoid arthritis group was increased and the blood pressure was significantly decreased. Superoxide dismutase activity of rheumatoid arthritis group was significantly increased by treatment. In addition, thoron and thermal treatment significantly enhanced the concanavalin A-induced mitogen response and increased the level of CD4-positive cells; it decreased the level of CD8-positive cells. The results suggest that thoron and thermal treatment activates antioxidative function. Furthermore, these findings suggest that thoron and thermal treatment prevents diabetic ketoacidosis and contributes to the prevention of aging-related diseases. Conclusion: Thoron and thermal therapy may be part of the mechanism for the alleviation of diabetes mellitus and rheumatoid arthritis. Iran. J. Radiat. Res., 2012; 9(4): 221-229

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DOI： 10.1007/s10753-011-9377-6

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We previously reported that radon inhalation activates antioxidative functions in the liver and inhibits carbon tetrachloride-induced hepatopathy in mice. In addition, it has been reported that reactive oxygen species contribute to alcohol-induced hepatopathy. In this study, we examined the inhibitory effects of radon inhalation on acute alcohol- induced hepatopathy in mice. C57BL/6J mice were subjected to intraperitoneal injection of 50% alcohol (5 g/kg bodyweight) after inhaling approximately 4000 Bq/m(3) radon for 24 h. Alcohol administration significantly increased the activities of glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT) in serum, and the levels of triglyceride and lipid peroxide in the liver, suggesting acute alcohol- induced hepatopathy. Radon inhalation activated antioxidative functions in the liver. Furthermore, pretreatment with radon inhibited the depression of hepatic functions and antioxidative functions. These findings suggested that radon inhalation activated antioxidative functions in the liver and inhibited acute alcohol- induced hepatopathy in mice.

DOI： 10.1155/2012/382801

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The enhanced release of reactive oxygen species from activated neutrophils plays important role in the pathogenesis of inflammatory bowel disease. We previously reported that radon inhalation activates antioxidative functions in various organs of mice. In this study, we examined the protective effects of radon inhalation on dextran sulfate sodium- (DSS) induced colitis in mice which were subjected to DSS for 7 days. Mice were continuously treated with air only (sham) or radon at a concentration of 2000 Bq/m(3) from a day before DSS administration to the end of colitis induction. In the results, radon inhalation suppressed the elevation of the disease activity index score and histological damage score induced by DSS. Based on the changes in tumor necrosis factor-alpha in plasma and myeloperoxidase activity in the colon, it was shown that radon inhalation suppressed DSS-induced colonic inflammation. Moreover, radon inhalation suppressed lipid peroxidation of the colon induced by DSS. The antioxidant level (superoxide dismutase and total glutathione) in the colon after DSS administration was significantly higher in mice treated with radon than with the sham. These results suggested that radon inhalation suppressed DSS-induced colitis through the enhancement of antioxidative functions in the colon.

DOI： 10.1155/2012/239617

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We examined the inhibitory effects of low-dose X-irradiation on mouse brain tissue with cold-induced injury by comparing tissue samples from three groups of mice: control, sham-irradiated cold-exposed, and X-ray-irradiated (0.5 Gy) cold-exposed mice. The water content in brain increased significantly in the sham-irradiated group following the cold-induced injury relative to the control group. However, water content in brain tissue from the X-ray-irradiated group was significantly lower than that from the sham-irradiated group. Levels of antioxidants, such as superoxide dismutase and glutathione, in brain tissue from the X-ray-irradiated group were higher than those from the sham-irradiated group. Moreover, the cold injury-induced cell death, particularly apoptosis, while low-dose irradiation inhibited cell death, especially among glial cells, but not numeral cells. These findings suggest that prior low-dose X-irradiation activated antioxidant function and inhibited cold-induced brain injury.

DOI： 10.1007/s10753-011-9293-9

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We assessed whether radon inhalation provided protection from carbon tetrachloride (CCl4)-induced hepatic and renal damage in mice. Mice were subjected to intraperitoneal injection of CCl4 after inhaling approximately 18 kBq/m(3) radon for 6 h. Radon inhalation significantly increased total glutathione (t-GSH) content and glutathione peroxidase (GPx) activity in the liver and kidney. Injection of CCl4 was associated with significantly higher levels of glutamic oxaloacetic transaminase (GOT) and alkaline phosphatase (ALP) activity and creatinine level in serum, and pretreatment with radon significantly decreased the GOT and ALP activity and creatinine level associated with CCl4 injection, suggesting that radon inhalation alleviates CCl4-induced hepatic and renal damage. The t-GSH contents and GPx activity in the liver and kidney of animals pretreated with radon were significantly higher than those of the CCl4-only group. These findings suggested that radon inhalation activated antioxidative functions and inhibited CCl4-induced hepatic and renal damage in mice.

DOI： 10.1007/s10753-010-9263-7

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We examined dose dependent or dose rate dependent changes of superoxide dismutase (SOD) activity using a new large-scale facility for exposing small animals to radon. Mice were exposed to radon at a concentration of 250, 500, 1000, 2000, or 4000 Bq/m(3) for 0.5, 1, 2, 4, or 8 days. When mice were exposed to radon at 2000 day.Bq/m(3), activation of SOD activities in plasma, liver, pancreas, heart, thymus, and kidney showed dose rate effects. Our results also suggested that continuous exposure to radon increased SOD activity, but SOD activity transiently returned to normal levels at around 2 days. Moreover, we classified the organs into four groups (1. plasma, brain, lung; 2. heart, liver, pancreas, small intestine; 3. kidney, thymus; 4. stomach) based on changes in SOD activity. Thymus had the highest responsiveness and stomach had lowest. These data provide useful baseline measurements for future studies on, radon effects.

DOI： 10.1269/jrr.10072

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To our knowledge, this paper is the most comprehensive review to cover most studies, published in the past three decades at least, of radon emanation measurements. The radon emanation fraction, a possibility of radon atoms generated in a material escaping from its grains, has been widely measured for a variety of materials. The aim of this review is to organize a huge number of such data accumulated. The representative values of the emanation fraction for minerals, rocks, soils, mill tailings and fly ashes were derived to be 0.03, 0.13, 0.20, 0.17 and 0.03, respectively. Current knowledge of the emanation processes was also summarized to discuss their affected factors. (C) 2011 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.apradiso.2011.06.009

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To our knowledge, this paper is the most comprehensive review to cover most studies, published in the past three decades at least, of radon emanation measurements. The radon emanation fraction, a possibility of radon atoms generated in a material escaping from its grains, has been widely measured for a variety of materials. The aim of this review is to organize a huge number of such data accumulated. The representative values of the emanation fraction for minerals, rocks, soils, mill tailings and fly ashes were derived to be 0.03, 0.13, 0.20, 0.17 and 0.03, respectively. Current knowledge of the emanation processes was also summarized to discuss their affected factors.

DOI： 10.1016/j.apradiso.2011.06.009

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Our previous studies showed the possibility that activation of the antioxidative function alleviates various oxidative damages, which are related to lifestyle diseases. Results showed that, low-dose X-ray irradiation activated superoxide dismutase and inhibits oedema following ischaemia-reperfusion. To alleviate ischaemia-reperfusion injury with transplantation, the changes of the antioxidative function in liver graft using low-dose X-ray irradiation immediately after exenteration were examined. Results showed that liver grafts activate the antioxidative function as a result of irradiation. In addition, radon inhalation enhances the antioxidative function in some organs, and alleviates alcohol-induced oxidative damage of mouse liver. Moreover, in order to determine the most effective condition of radon inhalation, mice inhaled radon before or after carbon tetrachloride (CCl(4)) administration. Results showed that radon inhalation alleviates CCl(4)-induced hepatopathy, especially prior inhalation. It is highly possible that adequate activation of antioxidative functions induced by low-dose irradiation can contribute to preventing or reducing oxidative damages, which are related to lifestyle diseases.

DOI： 10.1093/rpd/ncr189

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We examined differences in the radioactive characteristics among the main minerals forming granite materials. Using a non-toxic high-density agent, minerals were separated from rock (granite-gneiss) and soil (weathered granite) samples. The natural radioactivity ((238)U and (226)Ra) and radon emanation fraction of the minerals were then studied by gamma-ray spectrometry. The radon emanation fractions (27-43%) of the minerals from the soil were much higher than those (0.6-4.6%) of the rock minerals. Additionally, the emanation fractions differed greatly among the minerals separated from both the bulk rock and soil. These results were discussed in terms of the differences of surface area and radium distribution in the mineral grains. It was noticeable that a higher emanation fraction than expected for quartz was commonly observed in the rock and soil samples. We then estimated the contribution of each constituent mineral to the total radon exhalation from the bulk samples. The result depended not only on the radon emanation fraction, but also on the (226)Ra activity and the mineral content. Furthermore, using the obtained data, we also discussed the effect of grain size on radon emanation and why this has been reported to vary markedly in previous studies.

DOI： 10.1016/j.apradiso.2010.04.025

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The performance of imaging plates (IPs) has not been studied at temperatures lower than 0 degrees C. In the present study, an IP was irradiated with gamma rays emitted from the mineral monazite at temperatures between -80 and 30 degrees C to determine its fundamental properties. The IP response as a function of irradiation time was found to be linear, suggesting that the IP works properly at low temperatures. Fading, an effect which should be considered at temperatures of more than 0 degrees C, was not observed at -30 and 80 degrees C. Furthermore, the fading-corrected PSL value of the IP irradiated at 80 degrees C was lower than at other temperatures (30.5 and -30 degrees C). This can be explained by thermostimulated luminescence (TSL). Since the only intensive TSL peak in the temperature range from -80 to 30 degrees C is present at about -43 degrees C, some of the electrons trapped at F centers recombine with holes through the process of TSL before the stored radiation image is read out at room temperature. This finding suggests that the apparent sensitivity of the IP is lower at -80 degrees C although it is similar to sensitivities between -30 and 30 degrees C. This low sensitivity should be corrected to perform quantitative measurements. (C) 2010 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.apradiso.2010.03.020

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Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：TAYLOR & FRANCIS LTD  

This is the first report to provide radiation doses, arising from inhalation of radon itself, in mice and rats. To quantify absorbed doses to organs and tissues in mice, rats, and humans, we computed the behavior of inhaled radon in their bodies on the basis of a physiologically based pharmacokinetic (PBPK) model. It was assumed that radon dissolved in blood entering the gas exchange compartment is transported to any tissue by the blood circulation to be instantaneously distributed according to a tissue/blood partition coefficient. The calculated concentrations of radon in the adipose tissue and red bone marrow following its inhalation were much higher than those in the others, because of the higher partition coefficients. Compared with a previous experimental data for rats and model calculation for humans, the present calculation was proved to be valid. Absorbed dose rates to organs and tissues were estimated to be within the range of 0.04-1.4 nGy (Bq m(-3))(-1) day(-1) for all the species. Although the dose rates are not so high, it may be better to pay attention to the dose to the red bone marrow from the perspective of radiation protection. For more accurate dose assessment, it is necessary to update tissue/blood partition coefficients of radon that strongly govern the result of the PBPK modeling.

DOI： 10.1080/18811248.2010.9711649

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The present model represents an improvement on previous models of radon emanation from soil by incorporating soil grain size in addition to moisture. Monte Carlo simulation was employed in the calculation since it was difficult to mathematically express the radon emanation fraction for the present soil model. Grain size is one of the most important factors in describing the properties of soil. Grain size was demonstrated to affect the radon emanation fraction, depending on moisture content. Although the emanation fraction is generally considered to be proportional to grain size, the result of the model calculation suggested that the effect of grain size is not so simple. This study should serve as an initial step toward improving the modeling of this radon emanation. (C) 2010 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.apradiso.2009.11.070

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We examined differences in the radioactive characteristics among the main minerals forming granite materials. Using a non-toxic high-density agent, minerals were separated from rock (granite-gneiss) and soil (weathered granite) samples. The natural radioactivity (U-238 and Ra-226) and radon emanation fraction of the minerals were then studied by gamma-ray spectrometry. The radon emanation fractions (27-43%) of the minerals from the soil were much higher than those (0.6-4.6%) of the rock minerals. Additionally, the emanation fractions differed greatly among the minerals separated from both the bulk rock and soil. These results were discussed in terms of the differences of surface area and radium distribution in the mineral grains. It was noticeable that a higher emanation fraction than expected for quartz was commonly observed in the rock and soil samples. We then estimated the contribution of each constituent mineral to the total radon exhalation from the bulk samples. The result depended not only on the radon emanation fraction, but also on the Ra-226 activity and the mineral content. Furthermore, using the obtained data, we also discussed the effect of grain size on radon emanation and why this has been reported to vary markedly in previous studies. (C) 2010 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.apradiso.2009.12.036

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Some models have already been developed to explain the effect of moisture content on the radon emanation fraction of soil. For this purpose, "microscopic" soil models, which are easy to deal with mathematically but cannot take grain size into consideration, have been designed. These previous models consist basically of two opposite grain surfaces and pores between the grains. In the present study, in order to study the effect of not only moisture content but also grain size, we present a simple modeling approach based on two "macroscopic" soil models: (1) a single-grain model and (2) a multiple-grain model. The latter model represents a configuration of spherical grains packed in a simple cubic structure. Based on these soil models and general assumptions, the radon emanation fraction was calculated as a function of grain size or moisture content by Monte Carlo simulation. The results for the multiple-grain model show that the radon emanation fraction is markedly increased with grain sizes ranging from 10 to 100 inn and reaches a constant value of 50% when moisture content is 0% and the radium is uniformly distributed on the grain surface. Moreover, a drastic increase is seen at smaller grain sizes with increasing moisture content. From these results, we concluded that the calculation of radon emanation depends greatly on the pore size between a Ra-bearing grain and a neighboring grain. The validity of the model was also evaluated by comparison to experimental data. (C) 2010 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.radmeas.2010.01.010

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Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：JOURNAL CLINICAL BIOCHEMISTRY & NUTRITION  

We previously reported that low-dose X-irradiation alleviates ischemia-reperfusion injury such as mouse paw edema. In this study, we examined active changes in the biological function of mouse liver grafts in cold storage after low-dose X-irradiation. Mouse livers were sham-irradiated or were irradiated with 0.25, 0.5, 1.0, or 5.0 Gy of X-ray and stored for 4, 8, 24, or 48 h in preservation or saline solution. The results show that storage for 24 h in saline solution after 0.5 Gy irradiation significantly increased the activity of superoxide dismutase (SOD) and catalase. Following storage for 4, 8, or 48 h in preservation solution, lipid peroxide levels of the 0.5 Gy irradiated group were significantly lower than those of the sham irradiated group. Following storage for 24 h in preservation solution, the activity of SOD and catalase of the 1.0 Gy irradiated group were significantly higher than those of the sham irradiated group. Hepatocytes stored in saline solution were vacuolated. However, no vacuole formation was observed in hepatocytes stored in preservation solution. These findings suggest that low-dose irradiation significantly activates antioxidative functions of liver grafts. Moreover, the dose at which enhancement of antioxidative function occurs in livers stored in preservation solution, which contains glutathione, is significantly higher than that in saline solution.

DOI： 10.3164/jcbn.09-06

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To elucidate the radiosensitivity of an acatalasemic mouse, we examined the time and dose-dependency in the survival rates, the lymphocytes and the intestinal epithelial cells, and the antioxidant function after 3.0 to 12.0 Gy whole body irradiation. Results showed that no significant differences between acatalasemic mice and normal mice were observed in the survival rates and the histological changes in spleens and small intestine after each irradiation. The catalase activities in livers and spleens of acatalasemic mice were significantly lower than those of normal mice and the glutathione peroxidase activity in livers of acatalasemic mice was significantly higher than that of normal mice. At 10 days after 6.0 Gy irradiation, the catalase activities in livers of acatalasemic and normal mice and that in spleens of normal mice significantly decreased compared with no-irradiation control, and there were no differences between those catalase activities. The total glutathione content in acatalasemic mice was significantly higher than that in normal mice at 10 days after 6.0 Gy irradiation. These findings suggested that the radiosensitivity of acatalasemic mice in terms of whole body irradiation doesn't significantly differ from that of normal mice, probably due to compensated sufficient contents of glutathione peroxidase and total glutathione in acatalasemic mice.

DOI： 10.3164/jcbn.2008042

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The chemical composition was analyzed and the radioactivity, radon exhalation rate and emanation fraction were measured to investigate the characteristics of the granites sampled at Misasa and Badgastein, world famous for radon therapy. The Misasa granite was probably composed of quartz, albite and microcline. The Badgastein granite was probably composed of quartz and muscovite. The radon exhalation rates and emanation fractions of the Misasa granite were much higher than those of the Badgastein granite, regardless of the (226)Ra activity concentrations. (C) 2007 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.apradiso.2007.11.015

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In order to determine the best physical conditions for leaching more radon from minerals into water, we measured the leaching rate of radon from radioactive minerals under the conditions of some different grain sizes and water temperatures. Water temperature affected the leaching rate of radon although the grain size did not significantly affect it. Furthermore, we proposed ultrasonic irradiation to the mixture of a mineral and water as the method of leaching more radon. Ultrasonic irradiation was efficient to leach more radon from the mineral soaked in water because of ultrasonic cavitation. (C) 2007 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.radmeas.2007.07.009

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We have reported that low-dose, unlike high-dose, irradiation enhanced antioxidation function and reduced oxidative damage. On the other hand, ischemia-reperfusion injury is induced by reactive oxygen species. In this study, we examined the inhibitory effects of prior low-dose X-irradiation on ischemia-reperfusion injury in mouse paw. BALB/c mice were irradiated by sham or 0.5 Gy of X-ray. At 4 hrs after irradiation, the left hind leg was bound 10 times with a rubber ring for 0.5, 1, or 2 hrs and the paw thickness was measured. Results show that the paw swelling thickness by ischemia for 0.5 hr was lower than that for 2 hrs. At I hr after reperfusion from ischemia for I hr, superoxide dismutase activity in serum was increased in those mice which received 0.5 Gy irradiation and in the case of the ischemia for 0.5 or I hr, the paw swelling thicknesses were inhibited by 0.5 Gy irradiation. In addition, interstitial edema in those mice which received 0.5 Gy irradiation was less than that in the mice which underwent by sham irradiation. These findings suggest that the ischemia-reperfusion injury is inhibited by the enhancement of antioxidation function by 0.5 Gy irradiation.

DOI： 10.1269/jrr.07060

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To elucidate the characteristics of some radon hot springs, we simulated a hot spring by soaking the rocks for the radon therapy in water and measured the concentrations of radon and negative air ions in various conditions. In the results, the individual rock structure could contribute to radon leaching because the radon leaching rates were independent of the grain sizes. More negative air ions were generated by the wet rocks than by the dry rocks. (c) 2006 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.apradiso.2006.07.015

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We clarified that adequate oxygen stress induced by low dose irradiation activates not only chemical biological protective function, such as induction of the synthesis of superoxide dismutase, glutathione peroxidase, and heat shock protein 70, but also the biomembrane function, such as enhanced membrane fluidity and ATPase activity. It is possible that activation of these mechanisms alleviates in vivo oxidation injuries resulting in alleviation of pathologic condition, such as symptoms of hepatopathy and diabetes mellitus. Namely, adequate activation of the functions of the living body by low dose irradiation can contribute to suppressing aging and to preventing or reducing reactive oxygen species related diseases which are thought to involve peroxidation and have been regarded as the diseases for which radon spring water is an effective treatment. Clarification in detail of the mechanisms of these phenomena is required to understand the effects of low dose irradiation or radon inhalation on the functions of the living body, including adaptive response.

DOI： 10.3164/jcbn.39.114

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Exposure to water in hot springs containing thoron is thought to exercise beneficial effects on hypertension and diabetes mellitus. To put to a test this hypothesis we examined the time dependent changes in the levels of lipid peroxide, vasoactive- and diabetes associated substances in human blood in order to throw further light on the possible beneficial influence of thoron and thermal therapy on the mechanism of hypertension and diabetes mellitus. Every 2 days, nasal inhalation of vapor containing thoron was performed for 40 min. Blood samples were collected after each treatment at 1,2, and 3 weeks after the first treatment. Results show that the treatment decreased the lipid peroxide levels. The finding suggests that the treatment contributes to the prevention of peroxidation reaction related to hypertension and diabetes mellitus. Moreover, the changes in vasoactive-associated substances indicate an increase in tissue perfusion, suggesting that the treatment plays a role in alleviating hypertension. The treatment decreased the total ketone body levels and the finding suggests that the treatment contributes to the prevention of diabetes mellitus related to the insulin deficiency.

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We have previously determined by using immune-assay or bio-assay methods that low-dose irradiation enhances immune and anti-oxidation functions. In this study, we examined histological changes of lymphatic follicles at 4, 24, or 48 hrs after sham, 0.25, 0.5, or 15 Gy irradiation in the spleens of BALB/c mice, which are sensitive to radiation compared with other strains, and C57BL/6J mice, which are resistant to radiation, using hematoxylin-eosin staining for lymphatic follicles or methylgreen pyronin staining for plasma cells. Results show that the lymphatic follicles in the spleens of the two mouse strains decreased at 24 or 48 hrs after 15 Gy irradiation. The number of plasma cells in the spleens of sham irradiated BALB/c mice was greater than that of sham irradiated C57BL/6J mice. At 4 hrs after 0.25 Gy irradiation, plasma cells increased in the spleens of the two mouse strains. These findings suggest, by histology, that low-dose irradiation activates the plasma cells and enhances the immune function. Although those two mouse strains have different sensitivities to radiation, the above changes were similar in both time course and degree of response. Therefore, the phenomena observed may be common in mice.

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The catalase activities in the blood and organs of the acatalasemic (C3H/AnLCsb-Csb) mouse of the C3H strain are lower than those of the normal (C3H/AnLCsa-Csa) mouse. We examined the effects of post low-dose (0.5 Gy) X-ray irradiation which reduced the oxidative damage under carbon tetrachloride-induced hepatopathy in acatalasemic or normal mice. As a result, the 0.5 Gy irradiation after carbon tetrachloride administration decreased the glutamic oxaloacetic and glutamic pyruvic transaminase activity in the acatalasemic mouse blood to a level similar to that of the acatalasemic mouse blood not treated with carbon tetrachloride
this is in contrast to a high-dose (15 Gy) irradiation. In the same manner, pathological disorder was improved by 0.5 Gy irradiation. The fat degeneration in normal mice was quickly reduced, in contrast to acatalasemic mice. These findings suggest that low-dose irradiation after carbon tetrachloride administration accelerates the rate of recovery and that catalase plays an important role in the recovery from hepatopathy induced by carbon tetrachloride, in contrast to high-dose irradiation.

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To elucidate the mechanism of the radon therapy, we analyzed the radioactive characteristics of the minerals in the famous regions for the radon therapy. Using a high-purity germanium detector, we measured the sludge at the hot bathroom with a high concentration of radon at Misasa Medical Center of Okayama University Medical School, the hokutolite, which was the same kind of mineral at Tamagawa Hot Spring in Japan, and the mineral at the gallery of Badgastein in Austria, which are celebrated regions for the radon therapy. As a result, the ratios of the uranium series to the thorium series for the sludge of Misasa, the hokutolite, and the mineral of Badgastein were 22, 50, and 0.94, respectively. The sludge of Misasa and the hokutolite mainly included the radioelements of the uranium series, while the mineral of Badgastein included the radioelements of both series with almost the same ratio. The ratio of the mineral of Badgastein is similar to that of background (1.1). Furthermore, two kinds of minerals, which are commercially available for radon therapy, were measured using the same detector. The ratios for the two minerals were 0.26 and 0.20, namely, the two minerals included larger radioelements of the thorium series than those of the uranium series. (C) 2004 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.radmeas.2004.04.008

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN RADIATION RESEARCH SOC  

To clarify the mechanism by which radon hot springs prevent cancer or not, in this study, blood was collected from residents in the Misasa hot spring district and in a control district. The level of a representative cancer-suppressive gene, p53, and the activity of a representative antioxidant enzyme, superoxide dismutase (SOD), were analyzed as indices. The level of serum p53 protein in the males in the Misasa hot spring district was found to be 2-fold higher than that in the control district, which is a significant difference. In the females in the Misasa hot spring district, SOD activity was approximately 15% higher than that in the control district, which is also statistically significant, and exceeded the reference range of SOD activity despite advanced age. These results suggested that routine exposure of the residents in the Misasa hot spring district to radon at a concentration about 3 times higher than the national mean induces trace active oxygen in vivo, potentiating products of cancer- suppressive gene and antioxidant function. As the p53 protein level was high in the residents in the Misasa hot spring district, apoptosis of cancer cells may readily occur.

DOI： 10.1269/jrr.46.21

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：CHURCHILL LIVINGSTONE  

Radon therapy uses radon (Rn-222) gas, which mainly emits alpha-rays and induces a small amount of active oxygen in the body. We first examined the temporal changes in antioxidants, immune, vasoactive, and pain-associated substances in human blood by therapy to elucidate the mechanism of osteoarthritis in which radon therapy is used as a treatment. Results showed that radon inhalation enhanced the antioxidation and immune function, and the findings suggest that radon therapy contributes to the prevention of osteoarthritis related to peroxidation reactions and immune depression. Moreover, the changes in vasoactive and pain-associated substances indicated increases in tissue perfusion brought about by radon therapy, suggesting that radon inhalation plays a role in alleviating pain.
Perspective: The findings suggest that an appropriate amount of active oxygen is produced in the body after radon inhalation, and this contributes to the alleviation of the symptoms of active oxygen diseases such as osteoarthritis. (C) 2004 by the American Pain Society.

DOI： 10.1016/j.jpain.2003.09.005

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The radioactive and thermal effects of radon hot spring were biochemically compared under a sauna room or hot spring conditions with a similar chemical component, using the parameters that are closely involved in the clinic for radon therapy. The results showed that the radon and thermal therapy enhanced the antioxidation functions, such as the activities of superoxide dismutase (SOD) and catalase, which inhibit lipid peroxidation and total cholesterol produced in the body. Moreover the therapy enhanced concanavalin A (ConA)-induced mitogen response and increased the percentage of CD4 positive cells, which is the marker of helper T cells, and decreased the percentage of CD8 positive cells, which is the common marker of killer T cells and suppressor T cells, in the white blood cell differentiation antigen (CD8/CD4) assay. Furthermore, the therapy increased the levels of a atrial natriuretic polypeptide (alphaANP), beta endorphin, adrenocorticotropic hormone (ACTH), insulin and glucose-6-phosphate dehydrogenase (G-6-PDH), and it decreased the vasopression level. The results were on the whole larger in the radon group than in the thermal group. The findings suggest that radon therapy contributes more to the prevention of life-style-related diseases related to peroxidation reactions and immune suppression than to thermal therapy. Moreover, these indicate what may be a part of the mechanism for the alleviation of hypertension, osteoarthritis (pain), and diabetes mellitus brought about more by radon therapy than by thermal therapy.

DOI： 10.1269/jrr.45.83

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The catalase activities in blood and organs of the acatalasemic (C3H/AnLCs(b)Cs(b)) mouse of C3H strain are lower than those of the normal (C3H/AnLCs(a)Cs(a)) mouse. We examined the effects of prior low-dose (0.5 Gy) X-ray irradiation, which reduced the oxidative damage under carbon tetrachloride-induced hepatopathy in the acatalasemic or normal mice. The acatalasemic mice showed a significantly lower catalase activity and a significantly higher glutathione peroxidase activity compared with those in the normal mice. Moreover, low-dose irradiation increased the catalase activity in the acatalasemic mouse liver to a level similar to that of the normal mouse liver. Pathological examinations and analyses of blood glutamic oxaloacetic and glutamic pyruvic transaminase activity and lipid peroxide levels showed that carbon tetrachloride induced hepatopathy was inhibited by low-dose irradiation. These findings may indicate that the free radical reaction induced by the lack of catalase and the administration of carbon tetrachloride is more properly neutralized by high glutathione peroxidase activity and low-dose irradiation in the acatalasemic mouse liver.

DOI： 10.1269/jrr.45.89

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The increase in lipid peroxide levels in mice brain following Fe 3+ administration was about 50% of that when 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine (MPTP) was administered. This may be due to excessive oxidation by Fe3+, and was supported by the decrease in activities of antioxidant enzymes, such as superoxide dismutase (SOD), catalase and glutathione peroxidase (GPX), Na+,K+-ATPase activity and membrane fluidity after Fe3+ administration. Relatively low-dose X-ray irradiation (0.5 Gy) inhibited lipid peroxidation associated with Fe 3+ administration and restored the decreased activities of the above antioxidant enzymes and Na+K+-ATPase, and membrane fluidity to the levels in the non-Fe3+-administered group. In the purine metabolism system, uric acid decreased after Fe3+ administration, which may be due to transient impairment of the system for production of uric acid from xanthine by excessive oxidation by Fe3+. However, 0.5 Gy irradiation inhibited this decrease in uric acid, increasing its level to that in the non Fe3+-administrated group. This may be due to factors such as rapid recovery of the activities of the above antioxidant enzymes and Na+,K+-ATPase, and membrane fluidity after 0.5 Gy irradiation. In addition, since no changes were observed in xanthine and uric acid, increased inosine and hypoxanthine may have advanced to a salvage pathway leading to not xanthine but inosine 5′-monophosphate (IMP).

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The catalase activities in blood and organs of the acatalasemic (C3H/AnLCsbCsb) mouse of the C3H strain are lower than those of the normal (C3H/AnLCsaCsa) mouse. We conducted a study to examine changes in the activities of antioxidant enzymes, such as catalase, superoxide dismutase (SOD) and glutathione peroxidase (GPX), the total glutathione content, and the lipid peroxide level in the brain, which is more sensitive to oxidative stress than other organs, at 3, 6, or 24 hr following X-ray irradiation at doses of 0.25, 0.5, or 5.0 Gy to the acatalasemic and the normal mice. No significant change in the lipid peroxide level in the acatalasemic mouse brain was seen under non-irradiation conditions. However, the acatalasemic mouse brain was more damaged than the normal mouse brain by excessive oxygen stress, such as a high-dose (5.0 Gy) X-ray. On the other hand, we found that, unlike 5.0 Gy X-ray, a relatively low-dose (0.5 Gy) irradiation specifically increased the activities of both catalase and GPX in the acatalasemic mouse brain making the activities closer to those in the normal mouse brain. These findings may indicate that the free radical reaction induced by the lack of catalase is more properly neutralized by low dose irradiation.

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We examined the relationship between the induction of an increase in the level of glutathione and the elevation of natural killer (NK) activity in mouse splenocytes by a low dose of 7 rays. The glutathione levels in mouse splenocytes increased significantly between 2 h and 6 h after whole-body 7 irradiation at 0.5 Gy, peaked at 4 h, and then decreased almost to the level before irradiation by 12 h postirradiation. A significant enhancement of NK activity was found in the splenocytes obtained from whole-body-irradiated mice between 4 and 6 h postirradiation. Reduced glutathione (GSH) added exogenously to splenocytes obtained from normal mice enhanced both the total cellular glutathione content and the NK activity in a dose-dependent manner. Other precursors of de novo GSH synthesis, such as cysteine, N-acetylcysteine and oxidized glutathione, also increased the activity. These enhancements were completely blocked by buthionine sulfoximine, an inhibitor of de novo GSH synthesis. We conclude that the induction of endogenous glutathione in living cells immediately after low-dose T irradiation is at least partially responsible for the appearance of enhanced NK activity. (C) 2002 by Radiation Research Society.

DOI： 10.1667/0033-7587(2002)157[0275:EOGIBL]2.0.CO;2

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Because most of the diseases to which radon (222Rn) therapy is applied are related to activated oxygen, in this study the effect of the radioactivity of radon and the thermal effect were compared under a room or a hot spring condition with the same chemical component using as the parameters the activity of superoxide dismutase (SOD), which is an oxidation inhibitor, and lipid peroxide and low density lipoprotein (LDL)-cholesterol, which are closely involved in arteriosclerosis. Results show that the SOD activity was significantly increased, and the lipid peroxide and LDL-cholesterol levels were significantly decreased on days 6 and 7 of study. The results were about 2-fold larger in the radon group than in the thermo group. This suggests that the anti-oxidation function was more enhanced by radon therapy than by thermo therapy, and suggests that radon therapy may help to prevent the causes of life style-related diseases such as arteriosclerosis. These findings are important in understanding the mechanism of diseases in which radon therapy is used as treatment, and most of which are called activated oxygen-related diseases.

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Purpose: To examine the relation between the induction of an increased glutathione level and the elevated proliferative response of mouse splenocytes by a small dose of gamma -rays.
Materials and methods: Male ICR strain mice, 7 weeks of age, were divided into irradiated and non-irradiated control groups. irradiation was done with gamma -rays from a Cs-137 source at a dose of 50 cGy (1.11 Gy/min). Glutathione content in the splenocytes was measured using a modified spectrophotometric technique. Concanavalin A (Con A)-induced proliferative response of the splenocytes after whole-body gamma -ray irradiation was estimated from the H-3-thymidine incorporation into the cells.
Results: The glutathione level in mouse splenocytes increased 2 h after whole-body gamma -ray irradiation at 50 cGy, peaked at 4-h and thereafter decreased almost to the zero-time level by 12-h postirradiation. A significant enhancement of Con A-induced proliferation was observed in the splenocytes obtained from the whole-body-irradiated animals between 2 h and 6 h post-irradiation. Glutathione exogenously added to splenocytes obtained from normal mice enhanced the Con A-induced proliferation of splenocytes in a dose-dependent manner. This enhancement was completely blocked by buthionine sulfoximine, a specific inhibitor of the de novo pathway of glutathione synthesis.
Conclusions: The induction of endogenous glutathione immediately after low-dose gamma -ray irradiation is at least partially responsible for the enhancement of immune function, and may throw light on the mechanisms of carcinostatic effects induced by low dose ionizing radiation.

DOI： 10.1080/09553000050201136

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We examined the mechanisms of the elevation of glutathione level induced in macrophage-like RAW 264.7 cells by low closes of gamma-rays. The level increased soon after exposure of the cells to 50 cGy of gamma-rays, peaked between 3 hours and 6 hours and rearmed almost to the time 0 value by 24 hours post-irradiation. Doses between 25 and 100 cGy significantly increased the glutathione level at 4 hours post-irradiation. However there was no significant elevation at doses of more than 100 cGy or less than 25 cGy. When the effect of dose I-ate was examined at a constant absorbed dose of 50 cGy, dose rates Of more than 50 cGy/minute significantly increased the GSH level at 4 hours post-irradiation. It was also shown that the elevation of glutathione level in cells irradiated with low doses of gamma-rays followed the induction of mRNA coding for gamma-glutamylcysteine synthetase (gamma-GCS) a rate-limiting enzyme of the de novo glutathione synthesis pathway When the cells were exposed to the radiation in the presence of genistein, calphostin C or nifedipine, the elevations of glutathione and gamma-GCS mRNA expression were both mostly blocked. EGTA also strongly inhibited these elevations. These results suggest that the tyrosine kinase, calcium channel and protein kinase C activities play an essential role in the law-dose-radiation-induced elevation of cellular glutathione.

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We studied the effects of a single post whole-body low-dose irradiation (50 cGy of gamma-ray) on mice with ferric nitrilotriacetate (Fe3+-NTA)-induced transient hepatopathy. As a result, low-dose irradiation accelerated the rate of recovery. Based on the changes in glutamic oxaloacetic transaminase (GOT) activities, glutamic pyruvic transaminase (GPT) activities and lipid peroxide levels, it was shown that hepatopathy was improved by low-dose irradiation 3 h after Fe3+-NTA administration. This may be because of the enhancement of antioxidant agents such as total glutathione (GSH + GSSG), glutathione peroxidase (GPX), glutathione reductase (GR) and gamma-glutamylcysteine synthetase (gamma-GCS) by low-dose irradiation. These findings suggest that low-dose irradiation relieved functional disorders at least in the livers of mice with active oxygen species related diseases.

DOI： 10.1080/10715760000300221

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We examined the effects of irradiation (50 cGy of gamma-ray) reducing the oxidative damage in carbon tetrachloride (CCl4)-hepatopathy mice. We made pathological examinations and analyzed transaminase activity (glutamic oxaloacetic transaminase and glutamic pyruvic transaminase), lipid peroxide level and the activities of endogenous antioxidants in the mouse. The irradiation was found to accelerate the recovery. Based on pathological examination as well as changes in each transaminase activity and lipid peroxide levels, it was shown that hepatopathy improved 3 d after the irradiation. The activities of glutathione reductase and glutathione peroxidase rapidly elevated after irradiation, and the total glutathione content gradually increased in the irradiation group. Both activities of gamma-glutamylcysteine synthetase and catalase were higher than normal at all times after the irradiation and gradually increased. In addition, the gamma-glutamylcysteine synthetase activity changed In a similar fashion to the total glutathione content. However, superoxide dismutase activity in bath groups decreased and that of the irradiation group was significantly lower than that of the sham-irradiation group. These findings suggest that low-dose radiation relieved functional disorder at least in the liver of mice with active oxygen diseases. (C) 1999 Elsevier Science Inc.

DOI： 10.1016/S0891-5849(99)00180-X

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We examined the relationship between the induction of glutathione (GSH) level in macrophage-like RAW 264.7 cells by a low (adapting) dose gamma-rays and the cell damage caused by a lethal dose of gamma-rays at var-lolls intervals after the adapting dose. The reduced glutathione (GSH) level increased soon after exposure of the cells to 25 cGy of gamma-rays, peaked between 3 hl and 6 hr, and returned almost to the zero time (0 hr) bevel by 24 hr post-irradiation Cell damage was assessed by measuring the H-thymidine (H-3-TdR) incorporation into cellular DNA. gamma-Ray irradiation produced a dose- dependent cell damage in RAW cells, causing about 40% and 60% inhibition of H-3-TdR incorporation into DNA at 1.0 Gy and 2.0 Gy, respectively, as compared with non-irradiated cells. Treatment with the adapting dose of 25 cGy at I hr or 24 hr before the lethal irradiation was ineffective. However, pre-irradiation with 25 cGy at 3 hr or 6 hr prior to lethal irradiation inhibited the decrease of H-3-TdR incorporation into DNA, indicating a protective effect. GSH exogenously added to the medium also inhibited the cell damage induced by lethal doses of gamma-Rays in a dose-dependent manner. These results indicate that the induction of endogenous GSH in living cells immediately following low-dose gamma-Ray irradiation is at least partially responsible for the appearance of radioresistance to a subsequent lethal dose of radiation, and may make it possible to use higher doses of radiation in radiotherapy for tumor patients.

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We demonstrated that low-dose irradiation with 50 cGy of X-ray induces in vivo production of superoxide dismutase (SOD)-like substances and accelerates antioxidant activity. To elucidate the defense mechanism against X-ray radiation, we examined which components among these SOD-like substances, such as SOD, vitamin C and celuroplasmin, are produced by low-dose irradiation. Our study revealed that SOD-like specific activity hardly involved SOD-like substances other than SOD. Moreover, it is suggested that low-dose irradiation induced synthesis and production of SOD itself, leading to elevation of SOD-specific activity.

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Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

We examined the elevation of the reduced form of glutathione (GSH) level and the induction of mRNAs for proteins involved in the synthesis and regeneration of GSH in the liver of mice after low-dose gamma-ray irradiation. The liver GSH level increased soon after irradiation with 50 cGy of gamma-rays, reached a maximum at around 12 h post-treatment, The mRNA of gamma-glutamylcysteine synthetase (gamma-GCS), the rate-limiting enzyme for de novo synthesis for GSH, showed a small increase that peaked at 6 h after gamma-ray irradiation at a dose of 50 cGy. Only a small increase in gamma-GCS activity was observed throughout the 24-h post-irradiation period. In the case of glutathione reductase (GR), which is involved in the regeneration of GSH from the oxidized form (GSSG), the mRNA level peaked strongly at 1 h, while the activity peaked at twice the control level 12 h after irradiation. The level of mRNA for thioredoxin (TRX), which contributes to GSH biosynthesis by supplying cysteine to the de novo pathway, peaked at 1 h and declined thereafter, while the activity peaked at 3 h and then declined sharply. These results indicate that the increase in endogenous GSH immediately following low-dose gamma-ray irradiation is predominantly due to operation of the regeneration cycle and not de novo synthesis. We also examined the dependence of mRNA induction on the gamma-ray dose. (C) 1998 Elsevier Science B.V. All rights reserved.

DOI： 10.1016/S0304-4165(98)00043-9

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

We have previously demonstrated that the activity of superoxide dismutase (SOD), an antioxidant, is enhanced by low-dose X-ray irradiation in various organs of animals such as rats. Since SOD is an enzyme that mediates the dismutation of O-2(-) to H2O2, the question as to whether the resultant H2O2 is further detoxicated into H2O and O-2 or not must still be evaluated. Hence, we studied the effect of low-dose X-ray irradiation on the synthesis of glutathione peroxidase (GSHPx), which is an antioxidant that catalyzes this reaction. The results suggest that H2O2 produced by increased SOD activity can be detoxicated into H2O and O-2 due to simultaneous enhancement of the GSHPx activity by X-ray irradiation at 20 cGy, in contrast to irradiation at 400 cGy. The results also show the enhancement in enzyme activities by induction of their synthesis shortly after irradiation at 20 cGy, Moreover, as this phenomenon was observed in BALB/c mice (which are more radiation-sensitive compared to other mouse strains) and radiation-resistant C57BL/6NJcl mice, it was considered to be a common phenomenon in the rat spleen. (C) 1998 Elsevier Science B.V. All rights reserved.

DOI： 10.1016/S0304-4165(98)00021-X

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We examined the elevation of glutathione (GSH) levels in the liver of C57BL/6 female mice after low-dose r-ray irradiation and its inhibitory effect on CCl4-induced liver damage. The liver GSH level increased soon after irradiation with 50 cGy of gamma-rays, reached a maximum at around 12 post-treatment, and returned almost to the control level by 24 h. The activities of glutathione reductase, and glutathione peroxidase also showed the same pattern of change, while the activity of gamma-glutamylcysteine synthetase showed a gradual increase up to 24 h. The effect of pre-irradiation on CCl4-induced liver damage was also investigated. The activities of glutamic oxaloacetic transaminase and glutamic pyruvic transaminase in serum were markedly increased 12 h post-treatment with CCl4. Both increases were significantly suppressed by a single low-dose pre-irradiation. Malondialdehyde, a marker of lipidperoxidation, was also greatly elevated after CCl4 treatment, and its increase was suppressed by irradiation. These results suggest low-dose gamma-ray irradiation might be effective for the prevention of and/or therapy of various reactive oxygen species-related diseases including cancer.

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：PHYSIOL CHEM PHYSICS MED NMR  

Blood activities of hepatocellular enzymes such as lactate dehydrogenase (LDH), glutamic pyruvic transaminase (GPT) and glutamic oxalacetic transaminase (GOT) peaked at 12 hours after a single intraabdominal injection of ferric nitrilotriacetate (Fe3+-NTA) in rats. Enzymes such as alkaline phosphatase (ALP) and leucin amino peptidase (LAP) originating in the capillary bile ducts or bile secretory liver cells were also released into the blood between 6-24 hours after intraabdominal injection of Fe3+-NTA in rats. Furthermore, hyperoxidation of lipids occurred in rat hepatic cell membranes, reaching a peak 6 hours after intraabdominal injection of Fe3+-NTA. It was found that a single prior 0.5 Gy whole body X-ray irradiation significantly increased superoxide dismutase (SOD) activities and suppressed above-mentioned symptoms of transient hepatopathy in rats.

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The appearance of prostaglandins and thromboxane in mouse serum after X irradiation was observed by simultaneous quantitative analysis using gas chromatography/mass spectrometry/selected ion monitoring with stable isotope dilution methods. Mice of two strains (C57BL/CN Jcl and BALB/c) showed similar responses to X irradiation. In C57BL/6N Jcl mice, 0.2 Gy irradiation elicited a significant increase in generation of prostanoids: Immediately after irradiation, the 6-keto PGF(1) alpha:TXB2 ratio and the level of PGE(2) increased, after 20 min 6-keto PGF(1) alpha and PGE(2) increased, and after 4 h PGE(1) and PGE(2) increased. In BALB/c mice, generation of prostanoids was increased significantly immediately after irradiation (6-keto PGF(1) alpha, 6-keto PGF(1) alpha:TXB2 ratio, PGE(2)), and the increase was maintained from 20 min to 4 h (PGE(1), PGE(2)) after 0.2 Gy irradiation. In C57BL/6N Jcl mice, a significant increase in production of 9 alpha,11 beta-PGF(2) was observed at 20 min after irradiation. In BALB/c mice, a significant increase in 9 alpha,11 beta-PGF(2) was seen immediately after irradiation and was maintained for 20 min. In C57BL/6N Jcl mice, the level of 8-epi PGF(2) alpha was clearly increased 4 h after 4 Gy irradiation. A slight and slow increase was also seen after 0.2 Gy irradiation. In BALB/c mice, 8-epi PGF(2) alpha was increased significantly at 20 min and 4 h after 4 Gy irradiation. These results show that 0.2 Gy irradiation stimulates production of prostanoids related to the inflammatory response in mice. (C) 1998 by Radiation Research Society.

DOI： 10.2307/3579687

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This study examines the influence of low dose X-ray irradiation on purine nucleotide metabolites such as adenosine, inosine, hypoxanthine, xanthine and uric acid, and hence generation of ATP-mediated energy in mouse splenocytes. It was found that, unlike high dose irradiation which promotes membrane damage, low dose irradiation enhances the ability to regulate the energy metabolisms as reflected by the increase in Na+, K+-ATPase activity and the adequate activation of the above salvage pathway. Namely, the levels of adenosine, inosine and uric acid significantly increased, while the levels of xanthine and hypoxanthine decreased significantly. Moreover, the cysteine level and Superoxide dismutase activity significantly increased at a dosage of 20 cGy.

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Indications for treatment at the Misasa Hot Spring, a radon producing radioactive spring, include hypertension, diabetes mellitus and pain. To clarify its mechanisms of action on these conditions, we evaluated dynamic changes in blood components such as vasoactive substances after radon inhalation. Vasodilation, alleviation of diabetic symptoms and morphine-like analgesic effects were observed, suggesting that these changes constitute part of the mechanisms of the radon spring therapy on the above conditions.

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Authorship：Corresponding author   Language：English   Publishing type：Doctoral thesis  

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We examined changes in the blood pressure and the superoxide dismutase (SOD) activities in aortic tissue after gamma-irradiation to the chest regions of spontaneous hypertensive rats (SHR) and Wistar Kyoto rats (WKY), and obtained the following results. After 5 Gy irradiation, there was no change with time in the blood pressure in WKY rats, while a transient decrease (3 days later) was observed in SHR rats. The Cu/Zn-SOD activity in the aorta of SHR was less than that of WKY. 5 Gy irradiation induced an increase in the Cu/Zn-SOD activity in SHR nearly to the level observed in WKY, which remained unchanged upon irradiation. Therefore, unlike high-dose irradiation, irradiation at a relatively low-dose of 5 Gy to SHR appears to increase the aortic Cu/Zn-SOD activity, which is lacking in SHR, leading to a decrease in the blood pressure.

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Four hours after 0.25 Gy X-irradiation, the enzymatic activity of copper and zinc activated superoxide dismutase (Cu/Zn-SOD) in the spleen of mature rats showed a significant quantitative increase (by 25%); this was accompanied by a marked increase (by 70%) in the mRNA for this enzyme as compared to the control (sham irradiation) group. Irradiation had no effect on the enzymatic activity of manganese activated superoxide dismutase (Mn-SOD). Moreover, the expression of the mRNA for Mn-SOD was similar to that of the unirradiated control group. On the other hand, the enzymatic activity of both Cu/Zn-SOD and Mn-SOD in the liver of fetal rats showed a significant quantitative increase (by 15-35%); the expression of the mRNA for the two species of SOD increased (by 20-30%) at 4 hours after 1 Gy X-irradiation as compared to the control group. These findings suggest that the increase in SODmRNA level is due to novel transcription of SODmRNA by low dose irradiation.

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS  

We administered radon (Rn) to rabbits by inhalation and examined changes in the lipid peroxide (TBARS) level, superoxide dismutase (SOD) activity, and membrane fluidity in various organs to clarify the therapeutic effects of Rn. The lipid peroxide level of the brain was significantly decreased immediately after Rn inhalation for 90 min in both the low concentration group (about 7 ~ 10 kBq/liter) and the high concentration group (about 14 ~ 18 kBq/liter) as compared with that in the control group. It further decreased in the low concentration group but slightly recovered in the high concentration group 2 h after inhalation. The lipid peroxide level of the lung showed no change immediately after inhalation but decreased significantly in both groups 2 h after inhalation. With regard to SOD activity in the brain and lung, only that in the brain showed significant increase in the high concentration group immediately after inhalation; no other change was observed. Membrane fluidity, especially the fluidity of membrane protein, was significantly increased in the brains of both groups immediately after inhalation, and that 2 h after inhalation in the lung was significantly increased in both groups. These findings suggest that the inhalation of Rn at Rn springs contributes to the prevention of brain disorders related to peroxidation reactions by promoting these physiologic changes. © 1993 Academic Press, Inc.

DOI： 10.1006/abbi.1993.1177

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After a single exposure to doses ranging from 0.05 to 0.50 Gy, the SOD activities in immune organs of the irradiated rats, at 4 h after whole-body X irradiation, showed significant increases by 50 to 90% (hereinafter p &lt; 0.05) in comparison with the control groups. The dose in the brain and liver showed tendencies to increase by 30 to 50% for doses ranging from 0.50 to 2.50 Gy. The levels of TBARS (lipid peroxides) in immune organs decreased significantly by 20 to 50% in contrast with the control groups for doses ranging from 0.10 to 1.00 Gy. Decreases by 20 to 30% were observed in brains and livers for doses near 0.50 Gy. When the dose was 0.25 Gy, the SOD activities in the spleen showed a persistent radiation-induced increase for at least 12 weeks, livers for 8 weeks, brains and thymuses for 4 weeks, and bone marrows for about 1 week. The TBARS levels in the brain and thymus showed persistent decreases due to irradiation for at least 12 weeks, and those in bone marrows for 8 h.

DOI： 10.1016/0891-5849(91)90127-O

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Abstract

The liver’s susceptibility to oxidative stress after a combination of forced swim test (FST) and low-dose-rate γ-irradiation has been observed. Therefore, this study aims to clarify the effects of low-dose (0.1 and 0.5 Gy)/high-dose-rate (1.2 Gy/min) irradiation on combined oxidative stressors—liver damage associated with FST and alcohol administration. In addition, the effects of similar irradiation on FST-induced immobility, which induces psychomotor retardation, and antioxidative effects on the brain, lungs, liver and kidneys were investigated, and the results were compared with those of a similar previous study that utilized low-dose-rate irradiation. Low-dose/high-dose-rate (especially 0.5 Gy) irradiation temporarily worsened liver antioxidant function and hepatic function with FST- and alcohol administration-related oxidative damage; however, the damages improved soon after. In addition, the increase in total glutathione content in the liver contributed to the early improvement of hepatic functions. However, pre-irradiation did not suppress immobility during the FST. The results also suggested that the effects of low-dose/high-dose-rate irradiation on the antioxidant functions of each organ after the FST were different from those of low-dose/low-dose-rate irradiation. Overall, this study provides further insights into the effects of low-dose irradiation on exposure to a combination of different oxidative stressors. It will also contribute to the elucidation of dose rate effects on oxidative stress in the low-dose irradiation range.

DOI： 10.1093/jrr/rrad030

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Therapy using hot springs, including the high-level radioactive gas “radon”, is traditionally conducted as an alternative treatment for various diseases. Oxidative-stress-related diseases are inhibited by the enhancement of antioxidative functions following radon inhalation. We have reported that radon inhalation increased the level of anti-oxidants, such as glutathione (G-SH), in the brain and had a protective antioxidative effect against transient global cerebral ischemic injury. However, no studies have yet revealed the changes in G-SH associated substances after radon inhalation. In this study, we comprehensively analyzed several metabolites, focusing on G-SH. Mice were exposed to radon at concentrations of 200, 2000, or 20,000 Bq/m3 for 1, 3, or 10 days. We detected 27 metabolites in the mouse brains. The result showed that the L-methionine levels increased, whereas the levels of urea, glutathione, and sulfite ion decreased under any condition. Although the ratio of G-SH to oxidized glutathione (GS-SG) decreased, glutathione monosulfide (G-S-SH) and cysteine monosulfide (Cys-S-SH) increased after radon inhalation. G-S-SH and Cys-S-SH can produce a biological defense against the imbalance of the redox state at very low-dose irradiation following radon inhalation because they are strong scavengers of reactive oxygen species. Additionally, we performed an overall assessment of high-dimensional data and showed some specific characteristics. We showed the changes in metabolites after radon inhalation using partial least squares-discriminant analysis and self-organizing maps. The results showed the health effects of radon, especially the state of sulfur-related metabolites in mouse brains under the exposure conditions for radon therapy.

DOI： 10.3390/ijerph191710750

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In specific situations such as bathing in a radon spa, where the radon activity concentration in thermal water is far higher than that in air, it has been revealed that radon uptake via skin can occur and should be considered for more precise dose evaluation. The primary aim of the present study was to numerically demonstrate the distribution as well as the degree of diffusion of radon in the skin, with a focus on its surface layer (i.e., stratum corneum). We developed a biokinetic model that included diffusion theory at the stratum corneum, and measured radon solubility in that tissue layer as a crucial parameter. The implementation of the model suggested that the diffusion coefficient in the stratum corneum was as low as general radon-proof sheets. After a 20-min immersion in water, the simulated depth profile of radon in the skin showed that the radon activity concentration at the top surface skin layer was approximately 103 times higher than that at the viable skin layer. The information on the position of radon as a radiation source would contribute to special dose evaluation where specific target cell layers are assumed for the skin.

DOI： 10.3390/ijerph19137761

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<title>Abstract</title>
Radon inhalation decreases the level of lipid peroxide (LPO); this is attributed to the activation of antioxidative functions. This activation contributes to the beneficial effects of radon therapy, but there are no studies on the risks of radon therapy, such as DNA damage. We evaluated the effect of radon inhalation on DNA damage caused by oxidative stress and explored the underlying mechanisms. Mice were exposed to radon inhalation at concentrations of 2 or 20 kBq/m3 (for one, three, or 10 days). The 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels decreased in the brains of mice that inhaled 20 kBq/m3 radon for three days and in the kidneys of mice that inhaled 2 or 20 kBq/m3 radon for one, three or 10 days. The 8-OHdG levels in the small intestine decreased by approximately 20–40% (2 kBq/m3 for three days or 20 kBq/m3 for one, three or 10 days), but there were no significant differences in the 8-OHdG levels between mice that inhaled a sham treatment and those that inhaled radon. There was no significant change in the levels of 8-oxoguanine DNA glycosylase, which plays an important role in DNA repair. However, the level of Mn-superoxide dismutase (SOD) increased by 15–60% and 15–45% in the small intestine and kidney, respectively, following radon inhalation. These results suggest that Mn-SOD probably plays an important role in the inhibition of oxidative DNA damage.

DOI： 10.1093/jrr/rrab069

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<title>Abstract</title>
It is held that the skin dose from radon progeny is not negligibly small and that introducing cancer is a possible consequence under normal circumstances as there are a number of uncertainties in terms of related parameters such as activity concentrations in air and water, target cells in skin, skin covering materials, and deposition velocities. An interesting proposal has emerged in that skin exposure to natural radon-rich thermal water as part of balneotherapy can produce an immune response to induce beneficial health effects. The goal of this study was to obtain generic dose coefficients with a focus on the radon progeny deposited on the skin in air or water in relation to risk or treatment assessments. We thus first estimated the skin deposition velocities of radon progeny in air and thermal water based on data from the latest human studies. Skin dosimetry was then performed under different assumptions regarding alpha-emitting source position and target cell (i.e. basal cells or Langerhans cells). Furthermore, the impact of the radon progeny deposition on effective doses from all exposure pathways relating to ‘radon exposure’ was assessed using various possible scenarios. It was found that in both exposure media, effective doses from radon progeny inhalation are one to four orders of magnitude higher than those from the other pathways. In addition, absorbed doses on the skin can be the highest among all pathways when the radon activity concentrations in water are two or more orders of magnitude higher than those in air.

DOI： 10.1093/jrr/rrab030

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The forced swim test (FST) induces immobility in mice. Low-dose (high-dose-rate) X-irradiation inhibits FSTinduced immobility in mice due to its antioxidative function. We evaluated the effects of low-dose γ-irradiation at a low-dose-rate on the FST-induced depletion of antioxidants in mouse organs. Mice received whole-body low-dose-rate (0.6 or 3.0 mGy/h) of low-dose γ-irradiation for 1 week, followed by daily FSTs (5 days). The immobility rate on day 2 compared to day 1 was significantly lower in the 3.0 mGy/h irradiated mice than in sham irradiated mice. The FST significantly decreased the catalase (CAT) activity and total glutathione (t-GSH) content in the brain and kidney, respectively. The superoxide dismutase (SOD) activity and t-GSH content in the liver of the 3.0 mGy/h irradiated mice were significantly lower than those of the non-FST-treated mice. The CAT activity in the lungs of mice exposed to 3.0 mGy/h γ-irradiation was higher than that of non-FST treated mice and mice treated with FST. However, no significant differences were observed in the levels of these antioxidant markers between the sham and irradiated groups except for the CAT activity in lungs. These findings suggest that the effects of low-dose-rate and low-dose γ-irradiation on FST are highly organ-dependent.

DOI： 10.18926/AMO/61896

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DOI： 10.3769/radioisotopes.69.45

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我々はこれまで、低線量放射線はマウス諸臓器中で抗酸化機能を亢進し、酸化ストレス関連疾患を抑制することを報告してきた。しかしながら、それらの結果は対象疾患も低線量放射線による処置の条件も様々で、有効性が立証された治療法は確立されていない。そこで、本研究では、それらの結果から低線量放射線の健康効果を明らかにすることを目的とし、ラドン療法のような低線量放射線を活用した治療法の新規適応症を探索した。データの解析には自己組織化マップ(SOM)を用い、不安定な抗酸化機能の変化を自己組織化マップの曖昧な表現で視覚的に直感的に捉えることにより、出力された疾患抑制効果と抗酸化機能亢進の関連性を検討した。その結果、ラドン療法の適応症である疼痛への効果には明らかな線量依存性があることがわかり、肝疾患や脳疾患においても、線量依存性はないもののその効果を期待できると予測できた。本研究は、ラドン療法のような低線量放射線を活用した治療法の応用に貢献できると考える。(著者抄録)

DOI： 10.3769/radioisotopes.67.43

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The energy spectra of X-rays produced by an LiTaO3 single crystal have been measured at the pressures of 8 × 10−4−4 Pa. The energy spectra showed that the endpoint energy steadily increased with decrease of pressure at 2–4 Pa and gradually decreased with decrease of pressure at 0.1–2 Pa, and became almost constant below 0.1 Pa. The amount of X-rays steadily increased with decrease of pressure at 2–4 Pa and almost saturated below 0.5 Pa. The change of X-rays produced by the LiTaO3 single crystal was compared with the previous works and discussed in relation to the distance between the crystal surface and the target.

DOI： 10.1016/j.apradiso.2018.01.019

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We examined the effects of a reduced exposure dose on the quality of images from an angiography device augmented with a noise reduction algorithm. Before its clinical application, we compared the diameter of the discrimination limit of the hole with that in the conventional method by a visual evaluation with a contrast-detail (C-D) phantom imaged using the target dose. Based on the results, a reducible dose was determined and applied clinically. The sample population consisted of patients being followed up after percutaneous coronary intervention (PCI) for coronary artery disease; we evaluated the effects of the exposure reduction on image quality. A significant dose reduction was observed by the noise-reduction method compared to the conventional method; the radiation dose to the flat panel detector (FPD) could be reduced to 70 nGy per frame. Clinically, a dose reduction of approx. 40% was obtained while maintaining image quality almost equal to that of the conventional method.

DOI： 10.18926/AMO/55856

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The purpose of this study is to investigate the biokinetics of inhaled radon, radon activity concentrations in mouse tissues and organs were determined after mice had been exposed to about 1 MBq/m(3) of radon in air. Radon activity concentrations in mouse blood and in other tissues and organs were measured with a liquid scintillation counter and with a well-type HP Ge detector, respectively. Radon activity concentration in mouse blood was 0.410 +/- 0.016 Bq/g when saturated with 1 MBq/m(3) of radon activity concentration in air. In addition, average partition coefficients obtained were 0.74 +/- 0.19 for liver, 0.46 +/- 0.13 for muscle, 9.09 +/- 0.49 for adipose tissue, and 0.22 +/- 0.04 for other organs. With these results, a value of 0.414 for the blood-to-air partition coefficient was calculated by means of our physiologically based pharmacokinetic model. The time variation of radon activity concentration in mouse blood during exposure to radon was also calculated. All results are compared in detail with those found in the literature.

DOI： 10.1007/s00411-017-0682-9

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雄8〜9週齢ICRマウスを用いて強制水泳試験(FST)を行い、試験により誘導されるうつ病様症状に対するラドン吸入の効果について検証した。マウスの運動機能や不安状態に関してはオープンフィールド試験(OFT)により評価を行い、次に、FST誘導うつ病様症状に対するラドン前処理の効果(予防効果)およびラドン後処理の効果(治療効果)を調べると共に、生化学的検査により、脳内および血中モノアミン類、抗酸化物質の変化を調べた。その結果、予防効果の面では、FST前の2000Bq/m3の24hラドン吸入により、絶望行動が低下し、水泳意欲の向上が観察された。また、治療効果においては、2000Bq/m3の24hラドン吸入により、水泳意欲の向上とうつ病様症状への効果が認められ、水泳ストレスにより、脳内ノルエピネフリンとドーパミンが低下すると共に、FST誘導うつ病状態は血漿中スーパーオキシドジスムターゼ(SOD)活性低下および脳内脂質過酸化物(LPO)含量を増加させることが示された。さらに、ラドン吸入は脳組織内のモノアミン類(セロトニン、ノルエピネフリン、ドーパミン)を増加させると共に、FST前処理においてSOD活性を上昇させ、FST後処理におけるLPO含量を低下させた。以上の結果から、ラドン吸入は、マウス水泳ストレスにより誘導されるうつ病様症状を予防し、抑制することが明らかにされた。

DOI： 10.3769/radioisotopes.65.493

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Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

The energy spectra of X-rays produced by an LiTaO3 single crystal have been measured at pressures of 1-20 Pa. The energy spectra showed that the endpoint energy and the amount of X-rays gradually increased with the decrease of pressure at 5-8 Pa and abruptly increased around 4 Pa and below. A maximum endpoint energy of 70 keV was obtained using the LiTaO3 single crystal with 5 mm thickness at a pressure of 3 Pa. The change of X-rays produced by the LiTaO(3)single crystal was discussed in relation to the breakdown potential at the pressures. (C) 2016 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.apradiso.2016.08.003

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Oxidative stress in the body is considered an imbalance between the production and removal of reactive oxygen species (ROS). Ischemic acute renal failure, chronic renal failure, uremia, glomerulonephritis, and diabetic nephropathy are ROS-related diseases. In the veterinary field, a few studies of chronic kidney failure related to oxidative stress have been reported. Radon therapy has been used in Japan and Europe, and has been shown to have beneficial effects on ROS-related diseases such as bronchial asthma, arteriosclerosis, osteoarthritis, and pain-related diseases. We have demonstrated that radon inhalation increases antioxidative functions in kidney, and inhibits oxidative stress-induced kidney damage in animals. In addition, radon exposure systems for pets have already been developed. Therefore, we review the possible applications of radon therapy in veterinary care for oxidative stress-induced kidney damage.

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The possibility of antioxidant therapy has been reported for several diseases such as ischemic stroke. The therapy could also be applied for diseases caused by reactive oxygen species (ROS). It has been reported that ROS or free radicals may cause various types of hepatopathy, including alcoholic liver disease. Low dose (0.5 Gy) X- or γ- irradiation activates the antioxidative functions of the mouse liver and inhibits ROS- or free radical-induced hepatopathy. Radon therapy is performed mainly for pain-related diseases in Japan and Europe. Several clinical studies have been reported, but the possible mechanisms of the beneficial effects remain unknown. Recently, we have reported that the possible mechanism of radon therapy is the activation of antioxidative functions following radon inhalation. For example, radon inhalation inhibits and alleviates chronic constriction injury induced pain or inflammatory pain in mice due to the activation of antioxidative functions. In addition, although hepatopathy is not the main indication for radon therapy, our recent studies suggested that radon inhalation inhibits hepatopathy caused by ROS or free radicals. In this chapter, based on experiments with mice, we reviewed the possible applications of radon inhalation as an antioxidant therapy for hepatopathy from the viewpoints of recent antioxidant therapy, hepatopathy induced by ROS or free radicals, and the beneficial effects of radon inhalation for hepatopathy.

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This paper provides absorbed doses arising from radon gas in air retained in lung airway lumens. Because radon gas exposure experiments often use small animals, the calculation was performed for mice and rats. For reference, the corresponding computations were also done for humans. Assuming that radon concentration in airway lumens is the same as that in the environment, its progeny's production in and clearance from airways were simulated. Absorbed dose rates were obtained for three lung regions and the whole lung, considering that secretory and basal cells are sensitive to radiation. The results showed that absorbed dose rates for all lung regions and whole lung generally increase from mice to rats to humans. For example, the dose rates for the whole lung were 25.4 in mice, 41.7 in rats, and 59.9 pGy (Bq m(-3))(-1) h(-1) in humans. Furthermore, these values were also compared with lung dose rates from two other types of exposures, that is, due to inhalation of radon or its progeny, which were already reported. It was confirmed that the direct inhalation of radon progeny in the natural environment, which is known as a cause of lung cancer, results in the highest dose rates for all species. Based on the present calculations, absorbed dose rates of the whole lung from radon gas were lower by a factor of about 550 (mice), 200 (rats), or 70 (humans) than those from radon progeny inhalation. The calculated dose rate values are comparatively small. Nevertheless, the present study is considered to contribute to our understanding of doses from inhalation of radon and its progeny.

DOI： 10.1007/s00411-013-0478-5

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Biological response of exposure to radon progeny has long been investigated, but there are only few studies in which absorbed doses in lungs of laboratory animals were estimated. The present study is the first attempt to calculate the doses of inhaled radon progeny for mice. For reference, the doses for rats and humans were also computed with the corresponding models. Lung deposition of particles, their clearance, and energy deposition of alpha particles to sensitive tissues were systematically simulated. Absorbed doses to trachea and bronchi, bronchioles and terminal bronchioles, alveolar-interstitial regions, and whole lung were first provided as a function of monodisperse radon progeny particles with an equilibrium equivalent radon concentration of 1 Bq m(-3) (equilibrium factor, 0.4 and unattached fraction, 0.01). Based on the results, absorbed doses were then calculated for (1) a reference mine condition and (2) a condition previously used for animal experiments. It was found that the whole lung doses for mice, rats, and humans were 34.8, 20.7, and 10.7 nGy (Bq m(-3))(-1) h(-1) for the mine condition, respectively, while they were 16.9, 9.9, and 6.5 nGy (Bq m(-3))(-1) h(-1) for the animal experimental condition. In both cases, the values for mice are about 2 times higher than those for rats, and about 3 times higher than those for humans. Comparison of our data on rats and humans with those published in the literature shows an acceptable agreement, suggesting the validity of the present modeling for mice. In the future, a more sophisticated dosimetric study of inhaled radon progeny in mice would be desirable to demonstrate how anatomical, physiological, and environmental parameters can influence absorbed doses.

DOI： 10.1007/s00411-012-0431-z

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Adequate oxygen stress induced by low-dose irradiation activates biodefense system, such as induction of the synthesis of superoxide dismutase (SOD) and glutathione peroxidase. We studied the possibility for alleviation of oxidative damage, such as diabetes and nonalcoholic liver disease. Results show that low-dose γ-irradiation increases SOD activity and protects against alloxan diabetes. Prior or post-low-dose X- or γ-irradiation increases antioxidative functions in livers and inhibits ferric nitrilotriacetate and carbon tetrachloride-induced (CCl(4)) hepatopathy. Moreover, radon inhalation also inhibits CCl(4)-induced hepatopathy. It is highly possible that low-dose irradiation including radon inhalation activates the biodefence systems and, therefore, contributes to preventing or reducing reactive oxygen species-related diabetes and nonalcoholic liver disease, which are thought to involve peroxidation.

DOI： 10.5402/2012/

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DOI： 10.3769/radioisotopes.61.231

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The energy spectra of X-rays produced by an LiTaO3 single crystal have been measured at pressures of 5-50 Pa. The energy spectra showed that the amount of X-rays increased exponentially and the endpoint energy of the spectra increased linearly with the decrease of pressure at pressures of 10-25 Pa. A maximum endpoint energy of about 22 key was obtained using an LiTaO3 single crystal with 0.5 mm thickness at the pressure of 10 Pa. The maximum energy produced by the present experimental setup was estimated assuming that the LiTaO3 single crystal forms a parallel-plate capacitor. The estimated energy reasonably agreed with the energy obtained. The pressure dependence of the endpoint energy was discussed in relation to the breakdown potential at low pressures. (C) 2011 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.nima.2011.12.028

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DOI： 10.3769/radioisotopes.61.1

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Adequate oxygen stress induced by radon inhalation activates chemical biological protective functions, such as induction of the synthesis of superoxide dismutase and glutathione peroxidase. We studied the probability that activation of this function alleviated various oxidation injuries. The results showed that 1) Radon inhalation enhanced the antioxidative function and membrane fluidity in some mouse organs, and biogenic amine neurotransmitters in the rabbit brain; 2) To elucidate a more effective condition for radon inhalation, mice inhaled radon before carbon tetrachloride (CCl4) administration. The results show that radon inhalation alleviates CCl4-induced hepatopathy; 3) Radon inhalation elevated antioxidant enzymes in patients with bronchial asthma and osteoarthritis; 4) Radon inhalation alleviated the symptoms of hypertension, diabetes and pain in humans; 5) Radon inhalation elevated the p53 protein level and SOD activity in the blood of residents of the Misasa radon hot spring district. Moreover, we compared biochemically the radon effects and thermal effects on humans in radon hot spring therapy, the effects of thoron and thermal treatment for aging-related diseases in humans, and the effects of radon inhalation on acute alcohol-induced oxidative injury of the liver and brain in mice. These findings suggest that radon inhalation alleviates various reactive oxygen species-related injuries. It is highly possible that adequate activation of the functions of the living body by radon inhalation can contribute to preventing or reducing reactive oxygen species-related injuries (lifestyle diseases) which are thought to involve peroxidation. © 2012 by Nova Science Publishers, Inc. All rights reserved.

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DOI： 10.12950/rsm.10.1

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A radon test facility for small animals was developed in order to increase the statistical validity of differences of the biological response in various radon environments. This paper illustrates the performances of that facility, the first large-scale facility of its kind in Japan. The facility has a capability to conduct approximately 150 mouse-scale tests at the same time. The apparatus for exposing small animals to radon has six animal chamber groups with five independent cages each. Different radon concentrations in each animal chamber group are available. Because the first target of this study is to examine the in vivo behaviour of radon and its effects, the major functions to control radon and to eliminate thoron were examined experimentally. Additionally, radon progeny concentrations and their particle size distributions in the cages were also examined experimentally to be considered in future projects.

DOI： 10.1093/rpd/ncr100

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No research has been conducted on the radiation influence of tobacco on the alimentary system, although there have been some previous works on the respiratory system. In this study, the radioactive concentrations of Pb-210 and K-40 in a cigarette sample were first measured. The transfer factors of the nuclides from tobacco into smoke and solution (saliva and/or alcohol) were then examined. Moreover, the radiation doses from smoke inhalation were also evaluated. The radioactive concentrations of Pb-210 and K-40 in the cigarette tobacco were 0.01 and 0.3 Bq/cigarette. Since this Pb-210 activity and the Po-210 activity previously reported for the same sample were comparable, it can be concluded that there was a radioactive equilibrium between the 2 nuclides. The observed transfer factor of Pb-210 (12%) into smoke was almost the same as that of K-40 (15%), whereas the reported value for Po-210 (60%) was significantly higher. The radiation doses due to inhalation of cigarette smoke varied from organ to organ, depending on the organotropic properties of the nuclide. For example, the kidneys, respiratory tract, and spleen showed relatively high doses from Pb-210 and Po-210. The leaching rates indicated an inconsistent tendency related to solution types. This result could suggest that alcohol drinking, which is common in smokers, does not especially enhance the leaching characteristics.

DOI： 10.18926/AMO/45267

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DOI： 10.11252/dobutsurinshoigaku.19.113

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DOI： 10.5453/jhps.45.65

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Radioactive waste generated from research laboratories and other facilities is regulated by the Law Concerning Prevention from Radiation Hazards due to Radioisotopes etc. (Prevention Law). However, the Prevention Law does not provide the level of clearance or the procedures to follow for compliance monitoring. To assess radioactivity amounts for making decisions about clearance levels, the radioactivity levels in dry solid semi-combustible wastes generated from biomedical research, such as ⁵¹Cr-release assays, were measured and evaluated. Radioactivity of semi-combustible waste was 1.42-6.32% of the initial level. In comparison, records for the past 8 years in the Shikata Laboratory, Department of Radiation Research, Okayama University Advanced Science Research Center, indicated 7% to 90% of the initial radioactivity remained in the waste and was differed widely among researchers. This study determined an accurate radioactivity level in dry solid waste, which could lead to savings in disposal costs.<br>

DOI： 10.12950/rsm.9.7

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DOI： 10.3769/radioisotopes.57.241

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DOI： 10.12950/rsm2002.7.6

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DOI： 10.3769/radioisotopes.54.375

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被験者への吸入濃度を7000個/cm3あるいは20000個/cm3に調整したマイナスイオンによる自律神経系と循環器系への作用について,それぞれ皮膚電気活動と皮膚血流量を指標に測定した.その結果,皮膚血流量には有意な変化は見られなかったが,皮膚電気活動には有意な変化が認められた.これらより,マイナスイオンが少なくとも自律神経系などの生理活動に作用していることが示唆された

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Vascular smooth muscle cell (SMC) hyperplasia is known to be an important component in the pathogenesis of arteriosclerosis and restenosis. Although heparin has been well recognized as the representative molecule suppressing SMC growth in vitro, attempts to use heparin as a therapeutic anti-restenosis drug have not favorably influenced the angiographic or clinical outcome after angioplasty in some clinical trials. In this study, we have examined the effect of histidine-rich glycoprotein (HRG), a relatively abundant serum glycoprotein (similar to100 mug/ml in human serum), on the growth inhibition of cultured vascular SMC by heparin. Vascular SMC growth was significantly inhibited by heparin, giving nearly 85% inhibition with 100 mug/ml heparin. HRG reversed heparin-induced SMC growth inhibition in a dose dependent manner; 75% restoration of cell growth was observed when 100 mug/ml of HRG was co-added with 100 mug/ml heparin. Interestingly, micromolar concentrations of the zinc ion (0-10 muM), compatible with concentrations released from activated platelets, were found to enhance the restorative action of HRG. Western blot experiment demonstrated no significant amounts of the HRG moiety in fetal bovine serum, eliminating the possible contribution of contaminant HRG from culture media. These findings indicate that HRG, in combination with the zinc ion, plays a role in modulating the SMC growth response in pathophysiological states and explain the lack of success of heparin as a therapeutic anti-restenosis drug in clinical trials.

DOI： 10.1007/s00441-003-0737-x

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Histidine-rich glycoprotein (HRG) is a serum protein with possible pluripotent activities. In this study, a method for the quantification of rabbit histidine-rich glycoprotein (rHRG) was developed based upon the high affinity binding profile of rHRG to nickel-nitrilotriacetic acid (Ni-NTA), an improved chelation agent. When the binding profile of Ni-NTA for whole serum proteins was assessed by Western blotting, Ni-NTA exhibited the binding specificity only to rHRG even after washing with 20 mM imidazole, owing to the unusual amounts of histidine residues in rHRG. In the following experiments, the rHRG immobilized onto a microplate with specific antibody was determined spectrophotometrically with peroxidase-labeled Ni-NTA. This method permitted evaluation of rHRG concentrations ranging from 1.0 to 100 ng/ml, and was actually applicable to the monitoring of rHRG in Resource Q-fractionated serum preparations. Also, the co-addition of L-histidine into the incubation mixture significantly diminished the specific binding between rHRG and Ni-NTA. These findings indicate the potential usefulness of this method for the specific measurement of small amounts of rHRG and for understanding the roles of abundant histidine residues in rHRG-metal cation interaction. (C) 2002 Elsevier Science Inc. All rights reserved.

DOI： 10.1016/S0024-3205(03)00261-3

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The purpose of this study was to evaluate clinically T1-weighted spin-echo imaging (T1-SE) and T1-weighted opposed-phase gradient-echo (T1-opposed GRE) in medical examinations for vertebral metastases using 0.2 Tesla MRI. Twenty-one patients (9 males and 12 females, 105 vertebrae) with non-neoplastic lesions were assigned to the normal group (Group N), whereas 27 patients (16 males and 11 females, 133 vertebrae) with malignant metastatic vertebral lesions were assigned to the metastatic group (Group M). Using quantitative analysis, the contrast to noise ratio (CNR) for bone marrow to muscle in the region of interest (ROI) defined by the operator were determined with both groups, whereas the CNR for lesion to bone marrow was determined with Group M. In the subjective analysis, 275 vertebrae of 27 patients in Group M were evaluated. There were significant differences in the Group M between CNR values, T1-SE and T1-opposed GRE. The evaluation by T1-SE image alone was rated as 85.0% for sensitivity, 99.3% for specificity, respectively. On the other hand, evaluation rate only by T1-opposed GRE was 98.5% for sensitivity, 82.4% for specificity, respectively. T1-opposed GRE image is an effective tool for 0.2 Tesla MRI to examine metastatic bone marrow tumors. These findings indicate the necessity of both T1-SE and T1-opposed GRE in diagnostic imaging of vertebral metastases using 0.2 Tesla MRI.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN RADIATION RESEARCH SOC  

An increased systemic production of oxygen-free radicals by activated inflammatory cells is thought to be involved in the pathophysiology of asthma. The aim of this study is to evaluate the clinical effects of radon and thermal therapy on asthma in relation to antioxidant enzymes and lipid peroxide. Radon and thermal therapy were performed once a week. All subjects went to a hot bathroom with a high concentration of radon, and nasal inhalation of vapor from a hot spring was performed for 40 min once a day under conditions of high humidity. The room temperature was 48degreesC; the room radon concentration was 2,080 Bq/m(3). Blood samples were collected at 2 h, 14, and 28 days after the first therapy. A blood sample also was collected before the first therapy (at body temperature and background radon level) to be used as the control. The forced expiratory volume in one second (%FEV1) was significantly increased 28 days after the first therapy. Oil day 28, the catalase (CAT) activity was significantly increased in comparison with the control. The superoxide dismutase (SOD) activity was significantly increased compared to the control after first inhalation. On days 14 and 28, the lipid peroxide level was significantly decreased in comparison with the control. In conclusion, the present pilot study has shown that radon and thermal therapy improved the pulmonary function of asthmatics by increasing the reduced activities of antioxidant enzymes.

DOI： 10.1269/jrr.44.95

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We previously examined the effects of 0.5 Gy of γ- or X-irradiation on endogenous antioxidative materials, including glutathione, glutathione-related enzymes, superoxide dismutase and catalase in the liver, pancreas and brain of mice. An increase in the antioxidants was observed soon after the irradiation. We also demonstrated that the low-dose irradiation gave suppressive effects on reactive oxygen species (ROS)-related disease models such as acute hepatitis, type I diabetes and Parkinson's disease. These results suggested that the suppression or inhibition of the ROS-related diseases were made through the elevation of the antioxidants. We studied the effects of irradiation (0.5 Gy of γ-ray) reducing the renal oxidative damage in Fe3+ nitrilotri-acetate (NTA) injected mice. We examined transaminase activity, lipid peroxide level and those levels of antioxidants in the mouse. Both transaminase activities and lipid peroxide level accelerated decrease to normal level by the irradiation. The levels of total glutathione content and the activities of its related enzymes were slightly increased in the irradiated group. On the other hand, catalase (CAT) activity was significantly increased by the irradiation. These findings suggested that low-dose irradiation relieved functional disorder in the kidney of mice with ROS-related diseases, probably through enhancing antioxidant, in particular CAT activity. © 2002 Elsevier Science B.V.

DOI： 10.1016/S0531-5131(02)00151-6

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DOI： 10.3769/radioisotopes.51.66

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Language：Japanese   Publisher：岡山大学医学部保健学科  

空気中の放射性ヨウ素(125I)の濃度を簡便に測定する為に,活性炭濾紙を装着したホルダを50mlの注射器にセットした簡易な装置を考案・試作した.Nal(T1)ウェルタイプシンチレーションカウンタによって調べた活性炭濾紙での125Iの捕集効率は,44.5%であった.50ml注射器で1lの空気を活性炭濾紙に通し,その放射能とバックグランドをそれぞれ30分間,Nal(T1)ウェルタイプシンチレーションカウンタで測定した場合,空気中濃度限度の2.12倍の濃度であれば測定可能と考えられた.又,活性炭濾紙とプラスチックホルダからの気体状ヨウ素の漏れを防いで捕集効率を94.3%以上に上げることができれば,空気中濃度限度の125Iを測定できると考えられた.したがって,放射性ヨウ素の取り扱い中に,簡便に安価に空気中濃度の異常を検出する方法として有効と考えられた

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Fe3+-NTAを高濃度添加した肺癌由来の培養細胞の場合とは逆に,4μg/ml以下の低濃度で添加した場合,培養細胞の生育はよかった.更にこの培養細胞へFe3+-NTA添加前に0.25Gyの低線量X線を照射しておくと,その良好な生育が促進すると共に,LDHの遊離も抑制した

DOI： 10.3769/radioisotopes.50.37

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Pretreatment with nonlethal, low-dose irradiation has been shown to have a protective effect against oxidative injury in animal tissues, Since oxidative injury of tissues is known to be a major cause of many human diseases, we examined the effect of low-dose irradiation on the progression of type I diabetes in mice, Nonobese diabetic (NOD) mice were treated with gamma irradiation and the progression of the disease was monitored. An elevated level of glucose in urine was first detected at 15 weeks of age in the control NOD mice, whereas the detection was delayed as long as 7 weeks when the mice received a single dose of 0.5 Gy total-body irradiation between 12 and 14 weeks of age. The greatest effect was observed in the mice irradiated at 13 weeks of age, The increase in blood glucose and decrease in blood insulin were effectively suppressed by irradiation at 13 weeks of age. Both suppression of cell death by apoptosis and an increase in superoxide dismutase (SOD) activity were observed in the pancreas 1 week after irradiation. The results indicate that treatment with 0.5 Gy gamma rays suppresses progression of type I diabetes in NOD mice. This is the first report on the preventive effect of low-dose irradiation on disease progression. (C) 2000 by Radiation Research Society.

DOI： 10.1667/0033-7587(2000)154[0680:POTIDB]2.0.CO;2

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Purpose. To investigate the mechanism of the intracellular glutathione elevation induced by low-dose gamma -radiation.
Materials and methods: RAW 264.7 cells were irradiated with 1-400 cGy gamma -rays. Intracellular total glutathione content was determined by DTNB-recycling assay. Expression of mRNA for intracellular glutathione synthesis-related enzymes with or without treatment with Various inhibitors of second messengers of gene expression were examined by Northern blot analysis.
Results: Expression of mRNA for gamma -glutamylcysteine synthetase (gamma -GCS), a race-limiting enzyme of the de novo glutathione synthesis pathway, was elevated much more than that of glutathione reductase (GR) mRNA after exposure to 50 cGy gamma -rays. The low-dose gamma -ray-induced gamma -GCS mRNA elevation was abolished by inhibitors of protein kinase C and protein tyrosine kinase, as well as by the calcium ion channel blocker, nifedipine. Calcium-related reagents, such BAPTA/AM and EGTA, chelators of intra- and extracellular Ca2+ respectively, and a Ca2+ ionophore (A23187), also strongly blocked the elevation of gamma -GCS mRNA expression induced by gamma -rays.
Conclusions: The increase of intracellular glutathione in RAW 264.7 soon after low-dose gamma -ray exposure mainly occurs through the operation of the de novo pathway, following by the induction of gamma -GCS mRNA, for which elevation of intracellular calcium is required.

DOI： 10.1080/09553000050201127

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A simple method for purification of the histidine rich glycoprotein (rHRG) from rabbit sera was developed. The rHRG was purified by one-step affinity chromatography using the triphenylmethane dye 'acid fuchsin' as a specific ligand, which gave an overall yield above 80%. Interestingly, the binding of rHRG to the ligand required the divalent transition-metal ions such as Zn2+, Ni2+, and Co2+ at pH 9.5. In the presence of 0.5 mM ZnCl2, the binding was enhanced 15 times compared with that in the absence of ZnCl2. Bound rHRG was efficiently eluted from the affinity absorbent with 100 nM imidazole or histidine. Purified rHRG was homogeneous with an M(r) of 94 kDa when analyzed by SDS-PAGE, whereas isoelectric focusing revealed microheterogeniety with pI values ranging from 6.3 to 6.8. Blotting analysis with lectins specific for carbohydrate moieties and treatment with glycosidases demonstrated that rHRG is a highly N-glycosylated protein with diverse carbohydrate structures. (C) 2000 Academic Press.

DOI： 10.1006/abbi.2000.2032

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Nitric oxide (NO) functions as an endothelium-derived relaxation factor and regulates vascular resistance. Recent studies in this laboratory (Arch. Biochem. Biophys. 323, 27-32, 1995) revealed that the lifetime of NO significantly increased at physiologically low levels of oxygen concentrations and, hence, this gaseous radical strongly inhibited mitochondrial electron transport for a fairly long duration at low oxygen concentrations. The present work describes the effect of oxygen concentration on NO-induced relaxation and guanylate cyclase (GC) activity of endothelium-denuded aorta of the rat. Both NO and 2,2'-(hydroxynitrosohydrazono)bis-ethanamine (NOC18), an NO donor, induced the relaxa-tion of endothelium-denuded helical segments of rat aorta which were contracted by norepinephrine. NO-dependent relaxation of arterial specimens was enhanced by lowering oxygen concentration in the medium with concomitant increase in their cGMP levels. Anoxia induced the relaxation of the aorta by some NO-enhanceable and methylene blue-insensitive mechanism. These results suggested that local concentrations of oxygen might play important roles in the regulation of NO-dependent GC activity and vascular tonus of resistance arteries.

DOI： 10.1080/10715769900300311

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The elevation of endogenous thiol-related antioxidants and free radical scavenging enzymes in the brain of C57BL/6 female mice after low-dose gamma-ray irradiation and its inhibitory effect on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced brain damage were investigated. The brain level of the reduced form of glutathione (GSH) increased soon after irradiation with 50 cGy of gamma-rays, reached a maximum at 3 h post-treatment, and remained elevated until 12 h. Thioredoxin (TRX) was also transiently increased after irradiation. The activities of free radical scavenging enzymes, including Cu/Zn-superoxide dismutase, catalase and glutathione peroxidase, were significantly induced after irradiation as well. Cerebral malondialdehyde was remarkably elevated by MPTP treatment, and this elevation was suppressed by pre- irradiation (50 cGy). The contents of GSH and TRX were significantly decreased by MPTP treatment in comparison with those of the control group. These reductions both seemed to be attenuated by pre-irradiation with gamma-rays. These results suggest that low-dose gamma-ray irradiation induces endogenous antioxidative potency in the brain of mice and might be effective for the prevention and/or therapy of various reactive oxygen species-related neurodegenerative disorders, such as Parkinson's disease and Alzheimer's disease. (C) 1998 Elsevier Science Inc.

DOI： 10.1016/S0891-5849(98)00200-7

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First, we determined the cerebral localization of reduced glutathione (GSH) in normal mice by means of autoradiography using Tc-99m-meso-hexamethyl propylene oxime. A highly specific localization of GSH in the cerebellum and hippocampus was observed. Secondly, we measured the elevation of GSH level in the brain after low-dose gamma-irradiation. The cerebral GSH levels increased soon after irradiation with 50 cGy of gamma-rays, reaching a maximum at 3 h post-treatment, then remaining significantly higher than that of the non-irradiated control until 12 h and returning to the control level by 24 h. Thirdly, we examined the induction of the activities and the mRNAs of proteins involved in the synthesis and regeneration of GSH in the brain of mice subjected to low-dose gamma-ray irradiation. The level of mRNA for gamma-glutamylcysteine synthetase was significantly increased at 0.5 h, and remained high until 2 h post-irradiation (50 cGy). The level was transiently lowered to the non-irradiated control level at 3 h and slightly increased again after 6 h post-irradiation. gamma-Glutamylcysteine synthetase activity was significantly increased 3 h after irradiation, and remained high up to 24 h post-irradiation. As for glutathione reductase, the mRNA level was increased at 0.5 h, and peaked strongly at 2 h, while the enzyme activity was significantly increased at 6 h after irradiation, and continued to increase up to 24 h. The level of mRNA for thioredoxin, which contributes to GSH biosynthesis by supplying cysteine to the de novo pathway, peaked between 0.5 h and 2 h post-irradiation, and rapidly declined thereafter. The content of thioredoxin showed a transient decrease immediately after irradiation, but was then remarkably elevated, reaching a maximum at 3 h, and thereafter declining sharply. These results indicate that the increase in endogenous GSH in mouse brain soon after low-dose gamma-ray irradiation is a consequence of the induction of GSH synthesis related proteins and occurs via both the de novo synthesis and the regeneration pathways. (C) 1998 Elsevier Science B,V, All rights reserved.

DOI： 10.1016/S0006-8993(98)00832-4

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Although various stresses have been known to induce atrophy of the thymus, its pathogenesis remains to be clarified. To elucidate the mechanism of stress-induced atrophy of the thymus, possible involvement of thymocyte apoptosis was studied using rats which were exposed to cold environment. Exposure to cold temperature (5°C) for 4 h induced the fragmentation of thymocyte DNA in fasted rats but not in fed animals. Glucose levels in the blood and the body temperature of both fasted and fed rats markedly decreased during the exposure to cold temperature. Cold-stress significantly increased the plasma levels of corticosterone in fasted rats by some mechanism which was suppressed by feeding. The cold-stress-induced apoptosis was inhibited by either adrenalectomy or administration of RU486, a glucocorticoid receptor antagonist. Administration of glucose (7.5 g/kg body weight) also prevented the stress-induced apoptosis of thymocytes. These results suggested that cold-stress might enhance the secretion of glucocorticoid from the adrenal gland and induce apoptosis of thymocytes by some glucose-inhibitable mechanism.

DOI： 10.1016/S0928-4680(97)00021-7

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We studied the effect of low dose X-ray irradiation on the expression of stress proteins and gastric mucosal lesion. Low X-ray irradiation induced the expression of mRNA for heme oxygenase in adrenal and stomach. The expression hsp70 mRNA was also induced by low dose X-ray irradiation in the adrenal gland but not in the stomach. However, the expression of Mn-SOD mRNA was not changed in either tissue by low dose X-ray irradiation. Nor was WIR stress-induced gastric mucosal lesion prevented by pre-irradiation. These data suggest that low dose X-ray irradiation induced stress proteins in some specific tissues only. It did not prevent the gastric mucosal lesion.

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To elucidate the stimulative effect on the immune system, we studied the effect of acute low-dose whole-body X-irradiation on the mitogen-induced proliferative responses of rat splenocytes and thymocytes. Concanavalin A (Con A)-induced mitogen response of rat splenocytes 4 hours after 5 cGy irradiation was significantly higher (by 80%, p < 0.02) than that in sham-irradiated controls; whereas that of rat thymocytes did not show change after irradiation of 1-10 cGy. In the rats X-irradiated with doses greater than 25 cGy, Con A-induced mitogen responses of splenocytes and thymocytes were reduced. In a way similar to the Con A-induced mitogen response of splenocytes, the mitogen response of splenocytes induced by phytohemagglutinin (PHA) or lipopolysaccharide (LPS) was significantly increased by X-irradiation with 5 cGy (by 50%, p < 0.02). The enhancement of mitogen response of splenocytes was observed within a few hours after irradiation, being a temporary effect. After 5 cGy irradiation the level of leukotriene B4 (LTB4) in the supernatant fraction of the splenocyte suspension showed a significant increase (by 40%, p < 0.05).

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We previously found that low-dose X-ray irradiation or radon (weak alpha-ray) inhalation increases SOD activities and reduces lipid peroxide levels in various organs of 7-week-old rats or rabbits. In this study, we examined how the changes of SOD activity, lipid peroxide level, and membrane fluidity of the cerebral cortex in aged male Wistar rats (65 and 91 weeks old) were affected by low-dose X-ray irradiation (100 cGy or under) compared with those in 7-week-old rats, to elucidate the mechanism of aging inhibition. The following results were obtained: Although radiation sensitivity was observed to decreases with age, low-dose irradiation changed the Mn-SOD activity, lipid peroxide level, and membrane protein fluidity parameter of the cerebral cortex in the aged rats to be closer to those in the youth. These findings suggest that the increased SOD activity induced by low-dose irradiation enhances biomembrane functions, and that the decrease of lipid peroxide level enhances the membrane protein fluidity.

DOI： 10.1016/0891-5849(94)90132-5

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Total pages：175   Language：Japanese

CiNii Books

ASIN

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Authorship：Corresponding author  

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Authorship：Corresponding author   Publishing type：Article, review, commentary, editorial, etc. (bulletin of university, research institution)  

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Authorship：Corresponding author   Publishing type：Article, review, commentary, editorial, etc. (bulletin of university, research institution)  

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Authorship：Corresponding author   Publishing type：Research paper, summary (national, other academic conference)  

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Authorship：Corresponding author   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

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Authorship：Corresponding author   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

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Authorship：Corresponding author   Language：Japanese   Publishing type：Research paper, summary (national, other academic conference)   Publisher：(一社)日本放射線影響学会  

J-GLOBAL

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Authorship：Corresponding author   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

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Authorship：Corresponding author   Publishing type：Research paper, summary (national, other academic conference)  

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Authorship：Corresponding author   Language：Japanese   Publisher：(一社)日本ハイパーサーミア学会  

J-GLOBAL

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Authorship：Corresponding author   Publishing type：Lecture material (seminar, tutorial, course, lecture, etc.)  

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Authorship：Corresponding author   Publishing type：Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)  

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Authorship：Corresponding author   Publishing type：Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)  

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Authorship：Corresponding author   Publishing type：Research paper, summary (national, other academic conference)  

J-GLOBAL

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Authorship：Corresponding author   Publishing type：Article, review, commentary, editorial, etc. (bulletin of university, research institution)  

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Authorship：Corresponding author   Publishing type：Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)  

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Authorship：Corresponding author   Publishing type：Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)  

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Authorship：Corresponding author   Publishing type：Article, review, commentary, editorial, etc. (bulletin of university, research institution)  

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Authorship：Corresponding author   Publishing type：Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)  

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Authorship：Corresponding author   Publishing type：Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)  

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Authorship：Corresponding author   Publishing type：Article, review, commentary, editorial, etc. (bulletin of university, research institution)  

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Authorship：Corresponding author   Publishing type：Lecture material (seminar, tutorial, course, lecture, etc.)  

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Authorship：Corresponding author   Publishing type：Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)  

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Authorship：Corresponding author   Publishing type：Article, review, commentary, editorial, etc. (other)  

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Authorship：Corresponding author   Publishing type：Research paper, summary (national, other academic conference)  

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Authorship：Corresponding author   Language：English   Publishing type：Research paper, summary (international conference)   Publisher：ELSEVIER SCIENCE BV  

To simplify the analysis of the radioactive characteristics of the minerals for the radon therapy, we developed a simple method to calculate the ratio of the uranium series to the thorium series (U/Th) without using activity. The ratios calculated by this method agreed well with the ratios calculated using the activity. We applied this method to some minerals for the radon therapy. As a result, the U/Th&apos;s for the sludge of Misasa, the hokutolite, the mineral of Badgastein, and the two kinds of commercially available minerals were 22, 50, 0.94, 0.26, and 0.20, respectively. (c) 2004 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.ics.2004.09.029

Web of Science

Scopus

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Authorship：Corresponding author   Language：English   Publishing type：Research paper, summary (international conference)   Publisher：ELSEVIER SCIENCE BV