title: Peroxidase-mediated glutathione conjugation of benzo[a]pyrene-7,8-dihydrodiol is enhanced by benzo[a]pyrene phenols in vitro.
abstract: We reported previously that glutathione (GSH) is oxidized by peroxidases to a thiyl radical that can react with a number of chemicals, including the penultimate carcinogenic metabolite benzo[a]pyrene-7,8-dihydrodiol (7,8-B[a]PD), to give GSH conjugates. Here, we report that phenolic metabolites of benzo[a]pyrene (B[a]P) enhance the peroxidase-mediated formation of glutathione conjugates of 7,8-B[a]PD. The GSH conjugation of 7,8-B[a]PD in a horseradish peroxidase/peroxide system was increased over control values as follows: 9-OH-B[a]P by 4-fold, 7-OH-B[a]P by 3-fold, 1-OH-B[a]P by 2-fold. In contrast 3-OH-B[a]P was ineffective. A phenolic derivative of another polycyclic aromatic hydrocarbon (PAH), benz[a]anthracene, also enhanced GSH conjugation of 7,8-B[a]PD. The enhancement was dependent upon the presence of the phenol, horseradish peroxidase and peroxide. The phenolic compounds, including 3-OH-B[a]P, were also efficient reducing cofactors for the peroxidase. With the exception of 3-OH-B[a]P, the phenolic metabolites of PAH enhanced peroxidase-mediated formation of thiyl radical as detected by electron spin resonance spectrometry. Since both phenols and dihydrodiols are metabolites of B[a]P catalyzed by the cytochromes P450 system, enhancement of peroxidase-dependent 7,8-B[a]PD-GSH conjugation by phenols suggests a possible interaction between peroxidases and cytochromes P450 systems. This interaction may contribute to the detoxication of the penultimate carcinogenic PAH-dihydrodiols and other chemicals.
authors.affiliation: Laboratory of Molecular Biophysics, National Institute of Environmental, Health Sciences, Research Triangle Park, NC 27709.
authors.forename: G L
authors.initials: GL
authors.lastname: Foureman
authors.forename: K T
authors.initials: KT
authors.lastname: Knecht
authors.forename: T E
authors.initials: TE
authors.lastname: Eling
mesh_terms: D001564:Benzo(a)pyrene / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000494:pharmacology; D004101:Dihydroxydihydrobenzopyrenes / Q000378:metabolism*; D005609:Free Radicals; D005978:Glutathione / Q000378:metabolism*; D010544:Peroxidases / Q000494:pharmacology*; D010636:Phenols / Q000494:pharmacology*
chemical_list: D004101:Dihydroxydihydrobenzopyrenes; D005609:Free Radicals; D010636:Phenols; C017228:benzo(a)pyrene 7,8-dihydrodiol; D001564:Benzo(a)pyrene; D003577:Cytochrome P-450 Enzyme System; D010544:Peroxidases; D005978:Glutathione