title: 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 pregnancy 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-ethoxycoumarin 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 cigarette 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.
authors.affiliation: Lab. of Biochemistry, Korea Ginseng and Tobacco Research Institute, Yu Sung.
authors.forename: S Y
authors.initials: SY
authors.lastname: Kim
authors.forename: J H
authors.initials: JH
authors.lastname: Chung
authors.forename: K W
authors.initials: KW
authors.lastname: Kang
authors.forename: C O
authors.initials: CO
authors.lastname: Joe
authors.forename: K H
authors.initials: KH
authors.lastname: Park
mesh_terms: D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism*; D002417:Cattle; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis*; D004247:DNA / Q000378:metabolism*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000032:analysis; D008861:Microsomes / Q000201:enzymology*; D010105:Oxygenases / Q000032:analysis*; D010920:Placenta / Q000201:enzymology*; D011247:Pregnancy; D013950:Thymus Gland / Q000378:metabolism
chemical_list: D007527:Isoenzymes; D001564:Benzo(a)pyrene; D004247:DNA; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases