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Sister-chromatid exchange induction by indirect mutagens/carcinogens, aryl hydrocarbon hydroxylase activity and benzo[a]pyrene metabolism in cultured human hepatoma cells

Authors
Journal
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis
0027-5107
Publisher
Elsevier
Publication Date
Volume
109
Issue
1
Identifiers
DOI: 10.1016/0027-5107(83)90097-0

Abstract

Abstract 2 human hepatoma cell lines (C-HC-4 and C-HC-20), in which aryl hydrocarbon hydroxylase activity was induced with benz[ a]anthracene in vitro about 140- and 64-fold of the respective basal levels, yielded an increased frequency of sister-chromatid exchanges (SCEs) when exposed to benzo[ a]pyrene (BP), 7,12-dimethylbenz-[ a]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, aflotoxin B 1 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.

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