Effect of butylated hydroxyanisole on the metabolism of benzo[a]-pyrene and the binding of metabolites to DNA, in vitro and in vivo, in the forestomach, lung, and liver of mice

Abstract

The ability of three purified forms of rat liver cytochrome P-450 to metabolically activate benzo[a]pyrene, trans-benzo-[a]pyrene-7,8-dihydrodiol, 2-aminofluorene, afiatoxin B₁, dimethylnitrosamine, and a pyrolysis product of tryptophan(3-amino-l-methyl-5H-pyrido(4,3-b)indole) (Trp-P-2) to muta-genic 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 two major 3-MC inducible forms (cytochromes P-448₅₂ and P-448₅₅). Cytochromes P-448₅₂ and P-448₅₅ preferentially metabolize 2-aminofluorene and Trp-P-2 to mutagenic products. However, 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 afiatoxin B, to mutagenic products at a much faster rate than cytochrome P-450-PB. Dimethylnitrosamine was not activated by any of the isozymes tested.