Estrogenic/Antiestrogenic Activities of Benzo[a]pyrene Monohydroxy Derivatives

• Published in: Journal of Health Science 2001, Vol.47(6), pp.552-558
• Main Authors: Hirose, Toshiharu, Morito, Keiko, Kizu, Ryoichi, Toriba, Akira, Hayakawa, Kazuichi, Ogawa, Sumito, Inoue, Satoshi, Muramatsu, Masami, Masamune, Yukito
• Format: Article
• Language: English
• Subjects: benzo[a]pyrene; benzo[a]pyrene monohydroxy derivative; estrogen receptor α,β; estrogenic activity
• ISSN: 1344-9702; 1347-5207
• DOI: 10.1248/jhs.47.552

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)α and hERβ, 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 hERβ than to hERα. Using the yeast two-hybrid assay system, 1-, 2-, 3-, and 9-OH BaP induced β-galactosidase with hERβ but not with hERα. This suggested that these compounds were estrogenic. In the presence of 10-9 M 17β-estradiol, 8-OH BaP inhibited the induction of β-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.