Metabolic activation of bisphenol A by rat liver S9 fraction.

摘要

Bisphenol A (BPA) is a well-known endocrine-disrupting chemical found in the environment. To assess the metabolic modulation of estrogenic activity of BPA after ingestion, we investigated whether the incubation of BPA with rat liver S9 fraction results in metabolic activation or inactivation of estrogenic activity using a recombinant yeast expressing human estrogen receptor and MCF-7 transfected firefly luciferase plasmid for a reporter assay. When 0.1 mM BPA was incubated with rat liver S9 for 1 h, the estrogenic activity was increased about two to five times compared with that of the control, in which the S9 was inactivated prior to incubation. This metabolic activation was inhibited by SKF 525-A, an inhibitor of cytochrome P450. With increasing incubation time, the estrogenic activity increased time-dependently. Interestingly, however, the metabolic activation did not proceed with either microsomes or cytosol alone and was restored by a recombination of both fractions. The active metabolite was eluted at later retention time than that of BPA on HPLC with a reversed-phase column. Bisphenol B and methoxychlor were also activated by incubation with rat liver S9, whereas 4-tert-octylphenol and 4-nonylphenol, as well as 17beta-estradiol, were metabolically inactivated. The present results clearly indicate that BPA is metabolically activated in terms of estrogenicity under the conditions existing only with combined rat liver microsomes and cytosol.