title: The anti-estrogenic activity of selected polynuclear aromatic hydrocarbons in yeast expressing human estrogen receptor.
abstract: Polynuclear aromatic hydrocarbons (PAH) represent a large class of chemicals present in environment. We have used yeast strain ER(wt) expressing human estrogen receptor (hER) and an estrogen-sensitive reporter to characterize the estrogenic or anti-estrogenic activities of 21 PAHs. The PAHs did not exhibit estrogenic activity in yeast strain ER(wt). Four of the PAHs, dibenz[a,h]anthracene, 6-hydroxy-chrysene, 2,3-benzofluorene, and benzo(a)pyrene, inhibited estradiol-dependent reporter activity in strain ER(wt). A mutant hER lacking the amino terminus expressed in yeast was inhibited by the four PAHs to a lesser extent than the full-length hER. 6-hydroxy-chrysene, 2,3-benzofluorene, and benzo(a)pyrene, but not dibenz[a,h]anthracene, weakly displaced [3H]estradiol from the hER in a competition binding assay. A strong correlation between the inhibition of [3H]estradiol-binding from the hER and the reduction of hER-mediated transactivation in yeast was not observed. These observations suggest that the PAHs dibenz[a,h]-anthracene, 6-hydroxy-chrysene, 2,3-benzofluorene, and benzo(a)pyrene may antagonize activity in yeast by binding to an anti-estrogen binding site on the hER or by mechanisms independent of the hER.
authors.affiliation: Department of Environmental Health Sciences, Tulane University, New Orleans, Louisiana 70112, USA.
authors.forename: D Q
authors.initials: DQ
authors.lastname: Tran
authors.forename: C F
authors.initials: CF
authors.lastname: Ide
authors.forename: J A
authors.initials: JA
authors.lastname: McLachlan
authors.forename: S F
authors.initials: SF
authors.lastname: Arnold
mesh_terms: D001667:Binding, Competitive; D004958:Estradiol / Q000378:metabolism; D004965:Estrogen Antagonists / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D006801:Humans; D008145:Louisiana; D011084:Polycyclic Aromatic Hydrocarbons / Q000378:metabolism / Q000494:pharmacology*; D011960:Receptors, Estrogen / Q000187:drug effects* / Q000235:genetics; D011994:Recombinant Proteins / Q000187:drug effects; D014874:Water Pollutants, Chemical / Q000494:pharmacology*; D015003:Yeasts / Q000235:genetics
chemical_list: D004965:Estrogen Antagonists; D004967:Estrogens; D011084:Polycyclic Aromatic Hydrocarbons; D011960:Receptors, Estrogen; D011994:Recombinant Proteins; D014874:Water Pollutants, Chemical; D004958:Estradiol