Estrogenic/antiestrogenic activities of benzo[a]pyrene monohydroxy derivatives

Benzo[a]pyrene (BaP), a major environmental pollutant, is metabolized in vivo and produces many hydroxy derivatives. The estrogenic/antiestrogenic activities of twelve monohydroxy derivatives of BaP (1- through 12-OH species) were investigated using competition binding to human estrogen receptor (hER)alpha and herd, and the gene expression assay of the yeast two-hybrid system. BaP and 5-OH BaP did not hind to either hER, The other monohy-droxy derivatives bound to both hERs. These compounds bound more strongly to hER beta than to hER alpha. Using the cast two-hybrid assay system, 1-. 2-, 3-, and 9-OH BaP induced beta -galactosidase with hER beta but not with hER alpha. This suggested that these compounds were estrogenic. In the presence of 10(-9) M 17 beta -estradiol, 8-OH BaP inhibited the induction of beta -alactosidase. Because 8-OH BaP did not affect cell growth, it appeared to be an antiestrogen. The present study shows that most of the monohydroxy derivatives of BaP bind to estrogen receptors (ERs), and several of them have estrogenic or antiestrogenic activity.