title: [Assessment of hydroxylated metabolites of polychlorinated biphenyls and polychlorinated dibenzofurans as potential estrogens by yeast two-hybrid system].
abstract: The estrogenic activities of several hydroxylated metabolites of PCBs and PCDFs were investigated by yeast two-hybrid assay based on the ligand-dependent interaction of estrogen receptor with coactivator. For the hydroxylated PCBs, the order of estrogenic potency was 4-OH-2',4',6'-triCB > 4-OH-4'-monoCB, 4-OH-biphenyl. These compounds were evaluated as 10(3) to 10(4) less potent than 17 beta-estradiol based on the concentrations of test compounds showing 10% activity of 10(-7) M 17 beta-estradiol. 2-OH-3',4,4'-triCB, 4-OH-2',3,4'-triCB and 3-OH-/4-OH-2,2',5,5'-tetraCB, the metabolites of 2,2',5,5'-tetraCB were inactive as estrogens at the highest concentrations used in this study (10(-5) M). Also 4-OH-3,3',4',5-tetraCB, the metabolite of 3,3',4,4'-tetraCB was inactive as estrogen, indicating that this hydroxylated metabolite did not take part in the estrogenic activity of 3,3',4,4'-tetraCB. OH group at 4-position of biphenyl was necessary for the expression of estrogenicity, but one or two chloro-substitution adjacent to OH group inhibited the activity. For the hydroxylated PCDFs, 8-OH-2-monoCDF, 7-OH-3,4-diCDF, 8-OH-3,4-diCDF, 8-OH-3,4,6-triCDF and 3,8-(OH)2-2-monoCDF exhibited estrogenic activity. The estrogenic activity of 3,8-(OH)2-2-monoCDF was comparable to those of 4-OH-2',4',6'-triCB and 4-nonylphenol (mixture of compounds with branched sidechain). The order of activity was 3,8-(OH)2-monoCDF > 8-OH-3,4-diCDF, 7-OH-3,4-diCDF > 8-OH-2-monoCDF, 8-OH-3,4,6-triCDF. These compounds were evaluated as 2.5 x 10(3) to 3 x 10(4) less potent than 17 beta-estradiol. On the other hand, no estrogenic activity was observed for 2-OH-dibenzofuran, 3-OH-2,8-diCDF, 6-OH-3,4-diCDF and 9-OH-3,4-diCDF at concentrations as high as 10(-4) M. Substitution of OH group at 2(8)- or 3(7)-position of dibenzofuran and no chloro-substitution adjacent to OH group was required for the estrogenic activity.
authors.affiliation: Daiichi College of Pharmaceutical Sciences, 22-1, Tamagawa-cho, Minami-ku, Fukuoka 815-8511.
authors.forename: H
authors.initials: H
authors.lastname: Kuroki
authors.forename: S
authors.initials: S
authors.lastname: Yonekura
authors.forename: S
authors.initials: S
authors.lastname: Sakoda
authors.forename: K
authors.initials: K
authors.lastname: Fujino
authors.forename: H
authors.initials: H
authors.lastname: Nakaoka
authors.forename: H
authors.initials: H
authors.lastname: Aramaki
authors.forename: N
authors.initials: N
authors.lastname: Koga
authors.forename: J
authors.initials: J
authors.lastname: Nishikawa
authors.forename: T
authors.initials: T
authors.lastname: Nishihara
mesh_terms: D000818:Animals; D001572:Benzofurans / Q000737:chemistry / Q000378:metabolism*; D000072338:Dibenzofurans, Polychlorinated; D004967:Estrogens / Q000494:pharmacology; D006801:Humans; D006900:Hydroxylation; D011078:Polychlorinated Biphenyls / Q000737:chemistry / Q000378:metabolism*; D015003:Yeasts
chemical_list: D001572:Benzofurans; D000072338:Dibenzofurans, Polychlorinated; D004967:Estrogens; D011078:Polychlorinated Biphenyls