Metabolic activation of benzo(a)pyrene in SENCAR and BALB/c mouse embryo cell cultures.
The metabolism and DNA binding of benzo(a)pyrene [B(a)P] were compared in early passage mouse embryo cell cultures prepared from SENCAR mice, a strain especially susceptible to two-stage tumorigenesis, and BALB/c mice, a strain relatively resistant to two-stage tumorigenesis. Cultures from both strains metabolized similar amounts of B(a)P; however, the proportion of water-soluble metabolites formed was higher in the BALB/c cultures than in the SENCAR cultures. The major metabolites formed in cultures from both strains were B(a)P-9,10-diol, B(a)P-7,8-diol and the glucuronic acid conjugate of 3-hydroxy-B(a)P. The level of binding of B(a)P to DNA was greater in the SENCAR mouse embryo cell cultures than in the BALB/c cultures after 5, 24, and 48 hr exposure. The major B(a)P-DNA adduct formed in B(a)P-treated cultures from both strains was the adduct formed by reaction of (+)anti-B(a)P-7,8-diol-9,10-epoxide [anti-B(a)PDE, the isomer with the epoxide and the benzylic hydroxyl on opposite faces of the molecule] with the exocyclic amino group of deoxyguanosine. Immobilized boronate chromatography followed by high-performance liquid chromatography demonstrated the presence of small amounts of syn-B(a)PDE (the isomer with the epoxide and benzylic hydroxyl on the same face of the molecule)-DNA adducts. The proportions of these amounts were similar in cultures from both strains. The results suggest that SENCAR mouse embryo cell cultures may convert less B(a)P to water-soluble metabolites and more to DNA-binding metabolites than BALB/c mouse embryo cells.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism*; D001711:Biotransformation; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D004622:Embryo, Mammalian; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D012867:Skin / Q000378:metabolism; D012878:Skin Neoplasms / Q000139:chemically induced; D013045:Species Specificity
D001564:Benzo(a)pyrene; D004247:DNA