Metabolic activation of bisphenol A by rat liver S9 fraction

Citation
S. Yoshihara et al., Metabolic activation of bisphenol A by rat liver S9 fraction, TOXICOL SCI, 62(2), 2001, pp. 221-227
Citations number
37
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Toxicology
Journal title
TOXICOLOGICAL SCIENCES
ISSN journal
1096-6080 → ACNP
Volume
62
Issue
2
Year of publication
2001
Pages
221 - 227
Database
ISI
SICI code
1096-6080(200108)62:2<221:MAOBAB>2.0.ZU;2-5
Abstract
Bisphenol A (BPA) is a well-known endocrine-disrupting chemical found in th e environment. To assess the metabolic modulation of estrogenic activity of BPA after ingestion, we investigated whether the incubation of BPA with ra t liver S9 fraction results in metabolic activation or inactivation of estr ogenic activity using a recombinant yeast expressing human estrogen recepto r and MCF-7 transfected firefly luciferase plasmid for a reporter assay. Wh en 0.1 mM BPA was incubated with rat liver S9 for 1 h, the estrogenic activ ity was increased about two to five times compared with that of the control , in which the S9 was inactivated prior to incubation. This metabolic activ ation was inhibited by SKF 525-A, an inhibitor of cytochrome P450. With inc reasing incubation time, the estrogenic activity increased time-dependently . Interestingly, however, the metabolic activation did not proceed with eit her microsomes or cytosol. alone and was restored by a recombination of bot h fractions. The active metabolite was eluted at later retention time than that of BPA on HPLC with a reversed-phase column. Bisphenol B and methoxych lor were also activated by incubation with rat liver S9, whereas 4-tert-oct ylphenol and 4-non-ylphenol, as well as 17 beta -estradiol, were metabolica lly inactivated. The present results clearly indicate that BPA is metabolic ally activated in terms of estrogenicity under the conditions existing only with combined rat liver microsomes and cytosol.