Hormonal effects of several chemicals in recombinant yeast, MCF-7 cells and uterotrophic assays in mice

Abstract

Many methods have been developed for screening chemicals with hormonal activity. Using recombinant yeasts expressing either human estrogen receptor [Saccharomyces cerevisiae ER + LYS 8127 (YER)] or androgen receptor [S. cerevisiae AR + 8320(-)(YAR)], we evaluated the hormonal activities of several chemicals by induction of beta-galactosidase activity. The chemicals were 17 beta-estsadiol (E2), testosterone (T), rho-nonylphenol (NP), bisphenol A (BPA), genistein (GEN), 2-bromopropane (2-BP), dibutyl phthalate (DBP), di-(2-ethylhexyl) phthalate (DEHP), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and butylparaben (BP). To assess the estrogenicity of NP, the result of the in vitro recombinant yeast assay was compared with an E-screen assay using MCF-7 human breast cancer cells and an uterotrophic assay using ovariectomized mice. In the YER yeast cells, E2, NP, BPA, GEN, and BP exhibited estrogenicity in a dose-response manner, while TCDD did not. All the chemicals tested, except T, did not show androgenicity in the YAR yeast cells. The sensitivity of the yeast (YER) assay system to the estrogenic effect of NP was similar to that of the Ii-screen assay. NP was also estrogenic in the uterotrophic assay. However, in terms of convenience and costs, the yeast assay was superior to the E-screen assay or uterotrophic assay. These results suggest that the recombinant yeast assay can be used as a rapid tool for detecting chemicals with hormonal activities.