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Divergence of metabolic activation systems for short-term mutagenesis assays

Abstract

POLYCYCLIC hydrocarbons such as benzo(a)pyrene (BP) are prevalent environmental contaminants3 and are increasingly suspect as human carcinogens. They are routinely used as tumour agents in laboratory animals1 and in tissue culture assays2. These compounds are produced by the incomplete combustion of carbonaceous material such as fossil fuels used for transportation and industrial energy production. They are biologically inactive as parent compounds and require metabolic activation in tissue to produce a tumourigenically active species of the molecule. Activation is accomplished through the drug metabolising monooxygenase enzymes containing cytochrome P450 (refs 4–6), and activate the parent carcinogen to an intermediate epoxide7,8 which readily alkylates cellular macromolecules.

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SELKIRK, J. Divergence of metabolic activation systems for short-term mutagenesis assays. Nature 270, 604–607 (1977). https://doi.org/10.1038/270604a0

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