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标题：Modification of the Carcinogenic Potency of Quinoline, a Hepatocarcinogen, by Fluorine Atom Substitution : Evaluation of Carcinogenicity by a Medium-Term Assay
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作者：Ken-ichi SAEKI ; Minoru KADOI ; Yutaka KAWAZOE 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：1997
卷号：20
期号：1
页码：40-43
DOI：10.1248/bpb.20.40
出版社：The Pharmaceutical Society of Japan
摘要：The potent mutagen, 5-fluoroquinoline (5-FQ), and non-mutagenic 3-fluoroquinoline (3-FQ) were tested for hepatocarcinogenicity using a medium-term assay system employing quinoline, a moderately mutagenic hepatocarcinogen, as a reference. F344 male rats were given a single i.p. injection of a submanifestational dose of diethylnitrosamine (DEN, 200 mg/kg). Then, quinoline, 3-FQ, or 5-FQ at two doses (0.1% and 0.05%) was added to their diet for a period of 6 weeks, starting from 2 weeks after the DEN injection. Control groups were administered DEN alone. All rats were subjected to a partial (two-thirds) hepatectomy at the end of week 3 and sacrificed at the end of week 8. The number and areas of GST-P (placental glutathione S-transferase)-positive foci induced in the liver increased significantly as a result of treatment with 0.1% quinoline, and this increase was dramatic with 5-FQ at both doses, whereas no increases were noted with 3-FQ at either dose. Thus, the results of the medium-term carcinogenicity assay predicted that quinoline, a hepatocarcinogen, would be deprived of carcinogenicity by fluorine atom substitution at position 3, and would conversely be endowed with a higher carcinogenic capacity by substitution at position 5. A semi-quantitative relationship was demonstrated between carcinogenic and mutagenic potencies.
关键词：quinoline;hepatocarcinogen;carcinogenicity;medium-term carcinogenesis;fluorine substituent effect