Relationship Between Activities of Cytochrome P-450 Monooxygenases in Human Placental Microsomes and Binding of Benzo(A)Pyrene Metabolites to Calf Thymus DNA

ABSTRACT

Benzo(a)pyrene metabolism in human placental microsomes from smokers was studied. Benzo(a)pyrene metabolites were separated using high pressure liquid chromatographic technique. Reaction of benzo(a)pyrene with a microsomal fraction of placenta from individuals who smoke cigarettes during pregnency yields 7,8 dihydroxy benzo(a)pyrene as a major metabolite, while 3′-hydroxy benzo(a)pyrene, 4,5 dihydroxy benzo(a)pyrene and quinones constitute minor metabolites. The activities of arylhydrocarbon hydroxylase and 7-ethoxycoumarine deethylase exhibited much higher activities in smokers than in nonsmokers. Examination of specific binding of monoclonal antibodies to cytochrome P-450 isozymes in placental microsomes revealed that cigaratte smoking specifically enhanced the level of cytochrome P-450 c and d isozymes in human placental microsomes. Coincubation of ³H-benzo(a)pyrene and calf thymus DNA with placental microsomes yielded acid insoluble ³H-B(a)P from smokers, suggesting that cigarette smoking may induce placental enzymes which convert benzo(a)pyrene into ultimate metabolites to form carcinogen-DNA adducts.