Specificity of rat liver cytochrome P-450 isozymes in the mutagenic activation of benzo[a]pyrene, aromatic amines and aflatoxin B1

Abstract

The ability of 3 purified forms of rat liver cytochrome P-450 to metabolically activate [carcinogen] benzo[a]pyrene, trans-benzo[a]pyrene-7,8-dihydrodiol, 2-aminofluorene, aflatoxin B1, dimethylnitrosamine and a pyrolysis product of tryptophan(3-amino-1-methyl-5H-pyrido(4,3-b)indole) (Trp-P-2) to mutagenic products was examined using Salmonella typhimurium strains TA98 and G46 in a reconstituted monooxygenase system. The isozymes examined were cytochrome P-450-PB (the major phenobarbital inducible form), and the 2 major 3-MC [3-methylcholanthrene] inducible forms (cytochromes P-44852 and P-44855). Cytochromes P-44852 and P-44855 perferentially metabolize 2-aminofluorene and Trp-P-2 to mutagenic products. Only cytochrome P-44855 metabolizes benzo-[a]pyrene and its 7,8-dihydrodiol derivative to mutagenic products. Both cytochrome P-44852 and P-44855 metabolize aflatoxin B1 to mutagenic products at a much faster rate than cytochrome P-450-PB. Dimethylnitrosamine was not activated by any of the isozymes tested.