The role of highly purified cytochrome P-450 isozymes in the activation of 4-aminobiphenyl to mutagenic products in the Ames test

The role of cytochromes P-450 and P-447 in the activation of4-aminobiphenyl to mutagens in the Ames test was studied usingS9 preparations and highly purified isozymes. S9 preparationsfrom ß-naphthoflavone-pretreated rats were more efficientin converting 4-aminobiphenyl to mutagens than the correspondingpreparations from phenobarbitone-pretreated animals. Similarly,reconstituted systems comprising purified cytochrome P-447 weretwice as efficient as cytochrome P-450 in activating the carcinogen.Of all the known Phase I metabolites of 4-aminobiphenyl, onlythe N-hydroxy-derivative was mutagenic in the Ames test. Thesefindings indicate that arylamine N-hydroxylase is a cytochromeP-450 dependent enzyme, and the nature of the isozyme of thecytochrome is an important determinant of its mutagenicity.