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Exceptional mutagenicity of a benzo[a]pyrene diol epoxide in cultured mammalian cells

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Abstract

BENZO[a]PYRENE (BP) is one of a group of chemically inert carcinogens which, in order to exert their cytotoxic, mutagenic and carcinogenic effects, require metabolic activation by mixed function oxygenases (MFC) to products capable of covalent reaction with cellular macromolecules1–3. More specifically, it has been shown in mouse skin4 and various cultured mammalian cells5, that, in the case of DNA, the extent of this reaction correlates with the carcinogenic potency of the compound. The hypothesis that DNA is the important target for this series of hydrocarbons is further supported by evidence that the most carcinogenic members are also the most mutagenic towards hamster cells in vitro1. Here we present evidence that a diol epoxide derivative of BP is a powerful mutagen when applied to mammalian cells, and suggest therefore that this compound is the ultimate carcinogenic metabolite of BP.

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NEWBOLD, R., BROOKES, P. Exceptional mutagenicity of a benzo[a]pyrene diol epoxide in cultured mammalian cells. Nature 261, 52–54 (1976). https://doi.org/10.1038/261052a0

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  • DOI: https://doi.org/10.1038/261052a0

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