Selective Mutagenic Activation by Cytochrome P3-450 of Carcinogenic Arylamines Found in Foods

Abstract

Heterocyclic arylamines found in cooked foods including fish and beef are potent mutagens and carcinogens. The purpose of this investigation was to determine the specificity of cytochromes P₁-450 and P₃-450 toward the metabolic activation of these arylamines. We used a novel mutagenicity test system which combined human cells expressing either recombinant cytochrome P₁-450 or P₃-450 with Salmonella typhimurium to score mutants. Cytochrome P₃-450, a single iso-form of the cytochrome P-450 supergene family, bioactivated these food mutagens. Cytochrome P₁-450 showed little or no activation of these arylamines but was the isoform predominantly responsible for the activation of the aromatic hydrocarbon benzo-[α]pyrene-7,8-diol. This assay system should serve to define the specificities of individual cytochromes P-450 in the metabolic activation of carcinogens. [J Natl Cancer Inst 1989;81:223–227]