Benzo[a]pyrene carcinogenesis: a biochemical selection mechanism.

Separation of the metabolic products of benzo[a]pyrene has been readily accomplished by high-pressure liquid chromatography. This technique is uniquely suited for compounds labile to air and light and resolving positional isomers of phenolic or other types of oxygenated metabolites of this carcinogen. This procedure has been utilized to separate and compare benzo[a]pyrene activation and detoxification products between rat, mouse, and hamster hepatic microsomes and mouse and hamster embryo cell cultures. While metabolic profiles exhibited the same types of derivatives, marked quantitative variation was observed. Microsomal preparation produced large amounts of noncarcinogenic phenols, while intact cell metabolism favored diol formation. These results are in agreement with reactivation of metabolic diols as substrates for further activation to a more proximate carcinogenic species of benzo[a]pyrene and caution against extrapolating metabolic results from any single test system to other species or tissues.