研究者詳細 - 阪口　政清

論文 - 阪口　政清

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Active expression of p21 facilitates differentiation of immortalized human hepatocytes 査読

N. Kobayashi, T. Kunieda, M. Sakaguchi, T. Okitsu, T. Totsugawa, M. Maruyama, Y. Kosaka, M. Takesue, N. Shibata, N. Tanaka

Transplantation Proceedings 35 ( 1 ) 433 - 434 2003年

Maintenance of cold-preserved porcine hepatocyte function with UW solution and ascorbic acid-2 glucoside

M Takesue, M Maruyama, N Shibata, T Kunieda, T Okitsu, M Sakaguchi, T Totsugawa, Y Kosaka, A Arata, H Ikeda, J Matsuoka, T Oyama, M Kodama, K Ohmoto, S Yamamoto, Y Kurabayashi, Yamamoto, I, N Tanaka, N Kobayashi

CELL TRANSPLANTATION 12 ( 6 ) 599 - 606 2003年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SAGE PUBLICATIONS INC

Normal human hepatocytes are an ideal source of liver-targeted cell therapies, such as hepatocyte transplantation and bioartificial livers, but availability of human donor livers for liver cell isolation is severely limited. To effectively utilize scarce donor organs for cell therapies, it is of extreme importance to establish an efficient isolation technique and an effective cold preservation solution for transportation of isolated cells. A lateral segment of the liver was surgically resected from pigs weighing 10 kg and a four-step collagenase and dispase digestion was conducted. Isolated hepatocytes were subjected to 8-h cold storage on ice. The following preservation solutions were tested: 1) University of Wisconsin (UW) solution, 2) UW with 100 mug/ml of ascorbic acid-2 glucoside (AA2G), 3) 100% fetal bovine serum (FBS), and 4) Dulbecco's modified Eagle's medium (DMEM) supplemented with 100% FBS. The mean viability of porcine hepatocytes was 95.5 +/- 2.5% when isolated in three independent experiments. Viability, plating efficiency, membrane stability, and ammonia metabolic capacity of cold-preserved hepatocytes were significantly better maintained by the use of UW solution. When AA2G (100 mug/ml) was combined with UW solution, such parameters were further improved. It was explained by inhibition of caspase-3 activation and retention of ATP at high levels of hepatocytes preserved with UW solution containing AA2G. The present work demonstrates that a combination of UW solution with AA2G (100 mug/ml) would be a useful cold preservation means for the development of cell therapies.

DOI： 10.3727/000000003108747208

Improved conditions to induce hepatocytes from rat bone marrow cells in culture 査読

M Miyazaki, Akiyama, I, M Sakaguchi, E Nakashima, M Okada, K Kataoka, NH Huh

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 298 ( 1 ) 24 - 30 2002年10月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ACADEMIC PRESS INC ELSEVIER SCIENCE

Recent studies have revealed that bone marrow cells can develop into hepatocytes by in vivo transplantation under certain circumstances. However, little is known about the mechanism of bone marrow cell differentiation into hepatocytes. It is important to determine suitable culture conditions in which bone marrow cells will be differentiated into hepatocytes not only for understanding differentiation mechanisms but also for efficient amplification of hepatocyte-progenitor cells of bone marrow origin, this being a prerequisite for potential therapeutic use. In the present study, we found that hepatocyte growth factor (HGF) receptor (c-Met)- and a-fetoprotein-expressing cells were present in adult rat bone marrow. We also found that these cells also express hematopoietic stem cell markers, such as CD34, Thy-1, and c-Kit. Using an HGM medium with HGF and EGF, we succeeded in propagating hepatocyte-like cells induced from adult rat bone marrow in culture. These cells were immunocytochemically stained for albumin. By RT-PCR analysis of cultures containing the hepatocyte-like cells, we detected mRNAs of tryptophan-2,3-dioxygenase and tyrosine aminotransferase, markers of hepatocytes at a terminal differentiation stage. The present culture therefore can be a useful resource for cell transplantation therapy for liver diseases. (C) 2002 Elsevier Science (USA). All rights reserved.

DOI： 10.1016/S0006-291X(02)02340-9

Localization of S100C immunoreactivity in various human tissues 査読

A Kondo, M Sakaguchi, E Makino, M Namba, S Okada, NH Huh

ACTA MEDICA OKAYAMA 56 ( 1 ) 31 - 34 2002年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：OKAYAMA UNIV MED SCHOOL

Using 2-dimensional gel electrophoresis, we previously demonstrated that the S100C protein remarkably decreased after immortalization of normal human fibroblasts, and that this protein caused growth inhibition of human tumor cells when forcibly expressed in these cells, suggesting that S100C plays a significant role in tumor suppression. The present study was carried out to determine what type of human tissues express S100C protein,, and, subsequently, whether the S100C content in these tissues changes after normal cells have been transformed into cancer cells. We found that ductal cells in various tissues were positively stained with the S100C protein. In comparison, epithelial cells in digestive organs such as, the stomach, small intestine, and colon were not stained as strongly. When 14 pairs of human normal and cancerous tissues were stained with the antibody, decreases in the staining levels of S100C were observed in 6 kinds of:cancerous tissues-from the bronchus, mammary duct, renal tubule, prostate, uterus, and testis-in comparison with staining in their normal counterparts. These results suggest that S100C is a new tumor marker protein, the expression of which significantly decreases after malignant transformation of human tissues.

Antiproliferative activity of REIC/Dkk-3 and its significant down-regulation in non-small-cell lung carcinomas 査読

T Tsuji, Nozaki, I, M Miyazaki, M Sakaguchi, H Pu, Y Hamazaki, O Iijima, M Namba

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 289 ( 1 ) 257 - 263 2001年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ACADEMIC PRESS INC

We recently reported the cloning of the REIC/Dkk-3 gene, whose expression was shown to be downregulated in many human immortalized and tumor-derived cell lines [T. Tsuji et al. (2000) Biochem. Biophys. Res. Commun. 268, 20-24]. In the present study, we demonstrated that expression of the exogenous REIC/Dkk-3 gene in tumor cells inhibited cell growth. Furthermore, the level of REIC/Dkk-3 mRNA in normal human cells was lowest in the late G, phase during the cell cycle. Then we found that the expression of REIC/Dkk-3 was significantly down-regulated in surgically resected non-small-cell lung carcinomas. We determined the REIC/Dkk-3 locus on chromosome 11p15, where loss of heterozygosity has frequently been observed in human tumors. These findings indicate that REIC/Dkk-3 may function as a tumor suppressor. (C) 2001 Academic Press.

Up-regulation of S100C in normal human fibroblasts in the process of aging in vitro 査読

M Sakaguchi, M Miyazaki, T Kondo, M Namba

EXPERIMENTAL GERONTOLOGY 36 ( 8 ) 1317 - 1325 2001年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD

S100 proteins belonging to the EF-hand Ca2+ -binding protein family regulate a variety of cellular processes via interaction with different target proteins. Several diseases, including cancer and Alzheimer's disease, are related to a disorder of multifunctional S100 proteins, which are expressed in cell- and tissue-specific manners. We previously demonstrated that S100C could move to and accumulate in the nuclei of normal human fibroblasts but not in the nuclei of immortalized and neoplastic cells. In addition, we found that its nuclear accumulation resulted in suppression of DNA synthesis in normal cells at a confluent stage. In the present study, we investigated whether S100C was associated with cellular senescence in vitro. We found that S100C expression increased in normal human fibroblasts in the process of aging in culture and was accompanied by accumulation of its protein in the nuclei of senescent fibroblasts. In addition, the nuclear accumulation of S100C increased expression of a cyclin-dependent kinase inhibitor p21 (Sdil), a strong inhibitor of cell growth. These findings suggest that an increase in the cells having nuclear accumulation of S100C is closely related to the process of cellular senescence of normal human fibroblasts. (C) 2001 Elsevier Science Inc. All rights reserved.

Establishment of a human hepatocyte line (OUMS-29) having CYP 1A1 and 1A2 activities from fetal liver tissue by transfection of SV-10 LT 査読

KI Fukaya, S Asahi, S Nagamori, M Sakaguchi, C Gao, M Miyazaki, M Namba

IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL 37 ( 5 ) 266 - 269 2001年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SOC IN VITRO BIOLOGY

Immortalized human hepatocytes that can retain functions of drug-metabolizing enzymes would be useful for medical and pharmacological studies and for constructing an artificial liver. The aim of this study wa. to establish immortalized human hepatocyte lines having differentiated liver-specific functions. pSVneo deoxyribonucleic acid, which contains large and small T genes in the early region of simian virus 40, was introduced into hepatocytes that had been obtained from the liver of a 21-wk-old fetus. Neomycin-resistant immortalized colonies were cloned and expanded to mass cultures to examine hepatic functions. Cells were cultured in a chemically defined serum-free medium, ASF101, which contains no peptides other than recombinant human transferrin and insulin. As a result, air immortal human hepatocyte cell line (OUMS-29) having li er-specific functions was established from one of the 13 clones. Expression of CYP 1A1 arid 1A2 messenger ribonucleic acid by the cells was induced by treatment with benz[a]pyrene, 3-methylcholanthrene, and benz[a]anthracene. OUMS-29 cells had both the polycyclic aromatic hydrocarbon receptor (AhR) arid AhR nuclear translocator. Consequently, 7-ethoxyresorufin deethylase activity of the cells was induced time- and dose-dependent by these polycyclic aromatic hydrocarbons. This cell line is expected to he instrumental as an alternative method in animal experiments for studying hepatocarcinogenesis. drug metabolisms of liver cells, and hepatic toxicology,.

Overexpression of platelet-derived growth factor B and downregulation of PDGF-receptor alpha in human immortalized fibroblasts 査読

C Gao, M Miyazaki, T Kondo, T Tsuji, M Sakaguchi, M Namba

INTERNATIONAL JOURNAL OF ONCOLOGY 18 ( 4 ) 871 - 875 2001年4月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：PROFESSOR D A SPANDIDOS

Since immortalization of cells is critical in multistep carcinogenesis, efforts should be made to elucidate the mechanisms of the immortalization. To determine whether platelet-derived growth factor (PDGF) signal pathways play a role in immortalization of cells, we compared mRNA expressions of PDGFs and their receptors in three immortalized human fibroblast cell lines (SUSM-1, OUMS-24F, and KMST-6) with their normal parent cells. As a result, mRNA expression of PDGF-B (oncogene: c-sis) was upregulated in these immortalized cells. Unexpectedly, the expression of alpha- and beta -PDGF receptor genes was downregulated. PDGFR-alpha mRNA was remarkably decreased. When exogenous PDGFR-a was expressed transiently in the KMST-6 cells, the morphology of the cells resembled that of normal cells. These results suggest that the overexpression of PDGF-B (c-sis) and downregulation of PDGFR-alpha are related to the phenotypic characteristics of immortalized human cells.

Two-dimensional gel electrophoretic studies on the cellular aging: accumulation of alpha-2-macroglobulin in human fibroblasts with aging

T. Kondo, M. Sakaguchi, M. Namba

Experimental Gerontology 36 ( 3 ) 487 - 495 2001年3月

Identification of a phosphoprotein that is downregulated in immortalized human fibroblasts 査読

M Sakaguchi, M Miyazaki, T Kondo, T Tsuji, H Kouchi, M Namba

ELECTROPHORESIS 22 ( 1 ) 155 - 160 2001年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：WILEY-V C H VERLAG GMBH

Many lines of evidence indicate that the immortalization step is critical for the neoplastic transformation of normal human cells. Once normal human cells have been immortalized, they are relatively easily transformed into neoplastic cells. In order to understand these phenomena, patterns of protein phosphorylation in proliferating normal human fibroblast cell strains and their immortalized cell lines were compared by using two-dimensional polyacrylamide gel electrophoresis. It was found that the expression and phosphorylation levels of the human heat shock protein 27 (HSP27) were predominantly downregulated in the immortalized cells compared with those in their normal counterparts. In the normal cells, HSP27 expression and phosphorylation were markedly increased by physiological and nonphysiological stresses, such as serum addition, treatment with a carcinogenic agent like 4-nitroquinoline-1-oxide, and a high osmotic pressure. This may be a normal defense against acute changes of cellular environment and cytotoxic effects. However, these stresses had no effects on the expression and phosphorylation of HSP27 in the immortalized cells. These results suggest that an abnormal regulation of HSP27 expression and phosphorylation may be one of the reasons for easy neoplastic transformation of the immortalized cells by the treatment with carcinogenic agents.

Loss of nuclear localization of the S100C protein in immorialized human fibroblasts 査読

M Sakaguchi, H Yamada, T Tsuji, Y Inoue, M Miyazaki, T Tanaka, M Namba

RADIATION RESEARCH 155 ( 1 ) 208 - 214 2001年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：RADIATION RESEARCH SOC

It is well known that cancer develops through a multistep process, lit vitro transformation studies of normal human cells have shown that the immortalization step is critical for neoplastic transformation of cells. Furthermore, studies of cell fusion between normal and immortalized cells have indicated that the normal phenotype is dominant and the immortal phenotype is recessive. Thus we looked for cellular proteins that were down-regulated in immortalized human cells by two-dimensional gel electrophoresis to elucidate the mechanisms of immortalization of human cells. We found that the S100C protein was down-regulated in immortalized cells. This protein was localized in the cytoplasm of cells at the semiconfluent stage, while at the confluent stage it moved into the nuclei of normal cells but not into those of immortalized cells. Microinjection of an S100C antibody into normal confluent cells diminished the level of nuclear S100C protein, resulting in DNA synthesis. Taken together, loss of nuclear localization of the S100C protein, which may be related to DNA synthesis, is thought to be one of the mechanisms of immortalization, (C) 2001 by Radiation Research Society.

Hepatocyte growth factor induces differentiation of adult rat bone marrow cells into a hepatocyte lineage in vitro 査読

SH Oh, M Miyazaki, H Kouchi, Y Inoue, M Sakaguchi, T Tsuji, N Shima, K Higashio, M Namba

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 279 ( 2 ) 500 - 504 2000年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ACADEMIC PRESS INC

Bone marrow (BM) cells originally include alpha-fetoprotein (AFP)- and c-Met [a receptor for hepatocyte growth factor (HGF)]-expressing cells. In vitro treatment of BM cells with HGF induced albumin-expressing hepatocyte-like cells. Furthermore, those hepatocyte-like cells expressed cytokeratins 8 and 18, which are typically expressed in normal adult hepatocytes. These findings demonstrate that BM cells include AFP-expressing hepatic progenitor cells that can be differentiated into hepatocytes by HGF in culture, indicating that such cultures are useful resources for cell transplantation therapy for liver diseases. (C) 2000 Academic Press.

DOI： 10.1006/bbrc.2000.3985

Treatment of surgically induced acute liver failure with transplantation of highly differentiated immortalized human hepatocytes 査読

N Kobayashi, M Miyazaki, K Fukaya, Y Inoue, M Sakaguchi, H Noguchi, T Matsumura, T Watanabe, T Totsugawa, N Tanaka, M Namba

CELL TRANSPLANTATION 9 ( 5 ) 733 - 735 2000年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：COGNIZANT COMMUNICATION CORP

Primary human hepatocytes are an ideal source of hepatic function in bioartficial liver (BAL), but the shortage of human livers available for hepatocyte isolation limits this modality. To resolve this issue, primary human fetal hepatocytes were immortalized using simian virus 40 large T antigen. One of the immortal cell lines, OUMS-29, showed highly differentiated liver functions. Intrasplenic transplantation of OUMS-29 cells protected 90% hepatectomized rats from hyperammonemia and significantly prolonged their survival. Essentially unlimited availability of OUMS-29 cells supports their clinical use for BAL treatment.

Relationship between contact inhibition and intranuclear S100C of normal human fibroblasts 査読

M Sakaguchi, M Miyazaki, Y Inoue, T Tsuji, H Kouchi, T Tanaka, H Yamada, M Namba

JOURNAL OF CELL BIOLOGY 149 ( 6 ) 1193 - 1206 2000年6月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ROCKEFELLER UNIV PRESS

Many lines of evidence indicate that neoplastic transformation of cells occurs by a multistep process. For neoplastic transformation of normal human cells, they must be first immortalized and then be converted into neoplastic cells. It is well known that the immortalization is a critical step for the neoplastic transformation of cells and that the immortal phenotype is recessive. Thus, we investigated proteins downregulated in immortalized cells by two-dimensional gel electrophoresis. As a result, S100C, a Ca2+-binding protein, was dramatically downregulated in immortalized human fibroblasts compared with their normal counterparts. When the cells reached confluence, S100C was phosphorylated on threonine 10. Then the phosphorylated S100C moved to and accumulated in the nuclei of normal cells, whereas in immortalized cells it was not phosphorylated and remained in the cytoplasm. Microinjection of the anti-S100C antibody into normal confluent quiescent cells induced DNA synthesis. Furthermore, when exogenous S100C was compelled to localize in the nuclei of HeLa cells, their DNA synthesis was remarkably inhibited with increase in cyclin-dependent kinase inhibitors such as p16(Ink4a) and p21(Waf1) These data indicate the possible involvement of nuclear S100C in the contact inhibition of cell growth.

In vitro aging research in Japan 査読

T Tsuji, M Miyazaki, M Sakaguchi, M Namba

EXPERIMENTAL GERONTOLOGY 35 ( 3 ) 291 - 298 2000年5月

Establishment of a highly differentiated immortalized human hepatocyte cell line as a source of hepatic function in the bioartificial liver 査読

N Kobayashi, M Miyazaki, K Fukaya, Y Inoue, M Sakaguchi, H Noguchi, N Tanaka, M Namba

TRANSPLANTATION PROCEEDINGS 32 ( 2 ) 237 - 241 2000年3月

Prevention of acute liver failure in rats with reversibly immortalized human hepatocytes 査読

N Kobayashi, T Fujiwara, KA Westerman, Y Inoue, M Sakaguchi, H Noguchi, M Miyazaki, J Cai, N Tanaka, IJ Fox, P Leboulch

SCIENCE 287 ( 5456 ) 1258 - 1262 2000年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：AMER ASSOC ADVANCEMENT SCIENCE

Because of a critical shortage in suitable organs, many patients with terminal liver disease die each year before liver transplantation can be performed. Transplantation of isolated hepatocytes has been proposed for the temporary metabolic support of patients awaiting liver transplantation or spontaneous reversion of their liver disease. A major limitation of this form of therapy is the present inability to isolate an adequate number of transplantable hepatocytes. A highly differentiated cell line, NKNT-3, was generated by retroviral transfer in normal primary adult human hepatocytes of an immortalizing gene that can be subsequently and completely excised by Cre/Lox site-specific recombination. When transplanted into the spleen of rats under transient immunosuppression, reversibly immortalized NKNT-3 cells provided life-saving metabolic support during acute liver failure induced by 90% hepatectomy.

A REIC gene shows down-regulation in human immortalized cells and human tumor-derived cell lines 査読

T Tsuji, M Miyazaki, M Sakaguchi, Y Inoue, M Namba

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 268 ( 1 ) 20 - 24 2000年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ACADEMIC PRESS INC

Normal human cells stop proliferation after a certain number of cell divisions. This phenomenon is called cellular aging. The fact that the senescence phenotype is dominant and the immortal one is recessive indicates that immortalization of human cells may be caused by loss of functions of certain genes in normal cells. Based on this evidence, several cDNA clones whose expression was down-regulated during the immortalization process of human cells were isolated by the representative difference analysis (RDA) system in our laboratory. One of them, which was named REIC, was expressed to a lower degree in three human immortalized cell lines as compared with their parental normal counterparts, In addition, the expression of REIC was markedly lower in eight human tumor-derived cell lines (Hep3B and HuH-7 hepatocellular carcinomas, HuH-6 Clone 5 hepatoblastoma, HuCCT-1 cholangiocarcinoma, A549 lung cancer, HaCaT immortalized keratinocyte, HeLa cervical carcinoma, and Saos-2 osteosarcoma). In contrast, among the human tissues examined, the heart and brain, which contain a large number of post-mitotic cells, showed the highest expression of REIC. The full-length REIC cDNA revealed that the predicted protein is 350 amino acids in length and possesses coiled-coil tertiary structures in each of the amino- and carboxyl-termini. Furthermore, a search of the protein database revealed a match of this gene product with Dkk-3, which is a novel inhibitor of Wnt oncogene. These results indicate that the REIC cloned by us may function as a tumor suppressor. (C) 2000 Academic Press.

Transplantation of highly differentiated immortalized human hepatocytes to treat acute liver failure 査読

N Kobayashi, M Miyazaki, K Fukaya, Y Inoue, M Sakaguchi, T Uemura, H Noguchi, A Kondo, N Tanaka, M Namba

TRANSPLANTATION 69 ( 2 ) 202 - 207 2000年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS

Background. Temporary support of a damaged liver by a bioartificial liver (BAL) devise is a promising approach for the treatment of acute liver failure. Although human primary hepatocytes are an ideal source of hepatic function in BAL, shortage of human livers available for hepatocyte isolation is the limiting factor for the use of this modality. A clonal human hepatocyte cell line that can grow economically in culture and exhibit liver-specific functions should be an attractive solution to this problem.
Methods. To test this alternative, primary human fetal hepatocytes were immortalized using Simian virus 40 large T antigen. To investigate the potential of the immortalized cells for BAL, we transplanted the cells into the spleen of adult rats and performed a 90% hepatectomy 12 hr later.
Results, One of the cloned human liver cell lines, OUMS-29, showed highly differentiated liver functions. Intrasplenic transplanting of 20x10(6) OUMS-29 cells protected the animals from hyperammonemia and the associated hepatic encephalopathy, Survival was significantly prolonged in 90% of hepatectomized rats receiving GUMS-29 cells.
Conclusions. A highly differentiated immortalized human hepatocyte cell line, OUMS-29, was able to provide metabolic support during acute liver failure induced by 90% hepatectomy in rats. Essentially unlimited availability of OUMS-29 cells may be clinically useful for BAL treatment.

Establishment of a human hepatoma cell line, HLE/2E1, suitable for detection of P450 2E1-related cytotoxicity 査読

Isao Nozaki, Toshiya Tsuji, Masakiyo Sakaguchi, Yusuke Inoue, Ryuji Hirai, Akio Andou, Masahiro Miyazaki, Nobuyoshi Shimizu, Masayoshi Namba

In Vitro Cellular and Developmental Biology - Animal 36 ( 9 ) 566 - 570 2000年

記述言語：英語掲載種別：研究論文（学術雑誌）

By transfection of an expression vector of human cytochrome P450 2E1 (CYP2E1) into a human hepatoma cell line (HLE), a new cell line (HLE/2E1) that stably expresses activity of CYP2E1 has been established. The HLE/2E1 cell line expressed a higher level of CYP2E1 messenger ribonucleic acid than did the mother HLE cell line. CYP2E1 enzyme activity determined by a p-nitrophenol oxidation assay was also higher in HLE/2E1 cells than in HLE cells. In addition, the enzyme activity of the HLE/2E1 cells was increased by ethanol treatment. Exposure to acetaminophen (APAP) or buthionine sulfoximine (BSO) caused a greater decrease in viability of the HLE/2E1 cells than that of the HLE cells, as determined by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay. The cytotoxicity of APAP or BSO to HLE/2E1 cells was inhibited by the addition of ethanol or vitamin E. However, the cytotoxicity of both APAP and BSO was enhanced by 24-h preincubation of HLE/2E1 cells with ethanol. These results show that this cell line provides a useful model for studying catalytic properties of CYP2E1 and cytotoxic mechanisms of chemicals metabolized by CYP2E1.

DOI： 10.1007/BF02577524

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