Sister-chromatid exchange induction by indirect mutagens/carcinogens, aryl hydrocarbon hydroxylase activity and benzo[alpha]pyrene metabolism in cultured human hepatoma cells.
2 human hepatoma cell lines (C-HC-4 and C-HC-20), in which aryl hydrocarbon hydroxylase activity was induced with benz[alpha]anthracene in vitro to about 140- and 64-fold of the respective basal levels, yielded an increased frequency of sister-chromatid exchanges (SCEs) when exposed to benzo[alpha]pyrene (BP), 7,12-dimethylbenz[alpha]anthracene and 3-methylcholanthrene in vitro. Analysis of the metabolism of BP by these cells by high-pressure liquid chromatography revealed that both cell lines produced various BP metabolites including the proximate form BP-7,8-dihydrodiol which has been reported to be the most potent inducer of SCEs among the metabolites of BP. In addition, aflatoxin B1 and cyclophosphamide also induced SCEs in these cell lines. The above findings suggest that these cells may be capable of metabolizing a range of indirect mutagens/carcinogens into DNA-active forms. These cells may therefore serve as a useful test system in vitro for the detection of genotoxic agents, without the use of an exogenous activating system.
D016604:Aflatoxin B1; D000348:Aflatoxins / Q000494:pharmacology; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D001551:Benz(a)Anthracenes / Q000494:pharmacology; D001580:Benzopyrenes / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D002460:Cell Line; D003434:Crossing Over, Genetic / Q000187:drug effects*; D003520:Cyclophosphamide / Q000494:pharmacology; D004790:Enzyme Induction; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D009152:Mutagenicity Tests; D012854:Sister Chromatid Exchange / Q000187:drug effects*
D000348:Aflatoxins; D001551:Benz(a)Anthracenes; D001580:Benzopyrenes; D003520:Cyclophosphamide; D016604:Aflatoxin B1; D001189:Aryl Hydrocarbon Hydroxylases