The anti-estrogenic activity of selected polynuclear aromatic hydrocarbons in yeast expressing human estrogen receptor

Polynuclear aromatic hydrocarbons (PAH) represent a large class of chemicals present in the 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 [H-3]estradiol from the hER in a competition binding assay. A strong correlation between the inhibition of [H-3]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 estradiol activity in yeast by binding to an anti-estrogen binding site on the hER or by mechanisms independent of the hER. (C) 1996 Academic Press, Inc.