FORMATION OF 8-OXODEOXYGUANOSINE IN LIVER DNA AND HEPATIC INJURY BY PEROXISOME PROLIFERATOR CLOFIBRATE AND PERFLUORODECANOIC ACID IN RATS
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概要
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In this study, we examined whether the production of hydrogen peroxide by peroxisome proliferators causes oxidative DNA damage in the form of 8-oxodeoxyguanosine (8-oxodG) and hepatic injury, and whether it is related to their tumor-promoting or carcinogenic activities in female rats treated with the peroxisome proliferators clofibrate and perfluorodecanoic acid (PFDA). Clofibrate has tumor-promoting and carcinogenic activities, whereas PFDA does not. We also tested whether peroxisome proliferators directly induce mutagenic events in Salmonella typhimurium strains TA 98 and TA 1537. Rats were treated either by 5% clofibrate in diet or by an i.p. injection of corn oil containing 10 mg/kg body weight of PFDA every week for 2 or 8 weeks. 8-OxodG in liver DNA was analyzed by HPLC coupled with an electrochemical detector. Hepatic injury was evidenced by liver enlargement and by levels of serum enzymes, aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and hepatic γ-glutamylpeptidase (γ-GT) activity. Clofibrate and PFDA increased the activity of catalase about or less than 2-fold, whereas FAO activity was increased about 6 to 7-fold by clofibrate and about 3 to 4-fold by PFDA. Neither clofibrate nor PFDA induced mutation at any dose tested. Clofibrate significantly increased the formation of 8-oxodG, but PFDA only slightly increased. Serum AST and ALT levels, and hepatic γ-GT activity were not significantly changed at both time points, whereas the ratio of liver/body weight was significantly increased by clofibrate and PFDA at 8 weeks. These data imply that the magnitude of the production of hydrogen peroxide-generated FAO is related to the induction of oxidative DNA damage by peroxisome proliferators, and their tumor-promoting or carcinogenic activities. However, the effect of hydrogen peroxide in hepatic injury is not clear.
- 日本トキシコロジー学会の論文
- 1998-05-09
著者
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Kim Sun
College Of Pharmacy Seoul National University
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Kim Sun
College Of Pharmacy Chungbuk National University
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Yun Yeo
College Of Pharmacy Chungbuk National University
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YOO Hwan
College of Pharmacy and CBITRC, Chungbuk National University
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Yoo Hwan
College Of Pharmacy And Cbitrc Chungbuk National University
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Yoo H
Chungbuk National Univ. Chungbuk Kor
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Hong Jin
Coll. Of Pharmacy Chungbuk National Univ. Kor
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Hong Jin-tae
College Of Pharmacy Chunghuk National University
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Hwang Ji-hye
College Of Pharmacy Cbitrc Chungbuk National University
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Hong Jin
National Institute Of Toxicology Research Korea Food And Drug Administration
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Hong Jin
National Institute Of Safety Research
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Hong Jin
College Of Pharmacy And Cbitrc Chungbuk National University
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Kim Sun
College Of Medicine Korea University
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Jang Seung
National Institute Of Toxicology Research Korea Food And Drug Administration
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KANG Won
College of Pharmacy, Chungbuk National University
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Kang Won
College Of Pharmacy Chungbuk National University
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