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J.Health Sci., 47(6), 552-558, 2001
Estrogenic/Antiestrogenic Activities of Benzo[a]pyrene Monohydroxy Derivatives
Toshiharu Hirose,a Keiko Morito,a Ryoichi Kizu,b Akira Toriba,b Kazuichi Hayakawa,b Sumito Ogawa,c Satoshi Inoue,c Masami Muramatsu,d and Yukito Masamune*, a
aDepartment of Molecular and Cellular Biology and bDepartment of Hygienic and Analytical Chemistry, Faculty of Pharmaceutical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa 920-0934, Japan, cDepartment of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan, and dDepartment of Biochemistry, Saitama Medical School, 38 Morohongo, Moroyama-machi, Iruma-gun, Saitama 350-0451, Japan
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 hER beta, and the gene expression assay of the yeast two-hybrid system. BaP and 5-OH BaP did not bind to either hER. The other monohydroxy derivatives bound to both hERs. These compounds bound more strongly to hER beta than to hER alpha. Using the yeast 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 17beta-estradiol, 8-OH BaP inhibited the induction of beta-galactosidase. 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.
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