期刊
ENVIRONMENTAL HEALTH PERSPECTIVES
卷 109, 期 4, 页码 399-407出版社
US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
DOI: 10.1289/ehp.01109399
关键词
ER-CALUX; estrogenicity; flame retardants; hydroxylated compounds; polybrominated diphenyl ethers
Polybrominated diphenyl ethers (PBDEs) are used in large quantities as additive dame retardants in plastics and textile materials. PBDEs are persistent compounds and have been detected in wildlife and in human adipose tissue and plasma samples. In this study, we investigated the (anti)estrogenic potencies of several PBDE congeners, three hydroxylated PBDEs (HO-PBDEs), and differently brominated bisphenol A compounds in three different cell line assays based on estrogen receptor (ER)-dependent luciferase reporter gene expression. In human T47D breast cancer cells stably transfected with an estrogen-responsive luciferase reporter gene construct (pEREtata-Luc), 11 PBDEs showed estrogenic potencies, with concentrations leading to 50% induction (EC50) varying from 2.5 to 7.3 muM. The luciferase induction of the most potent HO-PBDE [2-bromo-4-(2,4,6-tribromophenoxy)phenol] exceeded that of estradiol (E-2), though at concentrations 50,000 times higher. As expected, brominated bisphenol A compounds with the lowest degree of bromination showed highest estrogenic potencies (EC50 values of 0.5 muM for 3-monobromobisphenol A). In an ER alpha -specific, stably transfected human embryonic kidney cell line (293-ER alpha -Luc), the HO-PBDE 4-(2,4,6-tribromophenoxy)phenol was a highly potent estrogen with an EC50 < 0.1 M and a maximum 35- to 40-fold induction, which was similar to E-2. In an analogous ER beta -specific 293-ER betas-Luc cell line, the agonistic potency of the 4-(2,4,6-tribromophenoxy)phenol was much lower (maximum 50% induction compared to E-2), but EC50 values were comparable. These results indicate that several pure PBDE congeners, but especially HO-PBDEs and brominated bisphenol A-analogs, are agonists of both ER alpha and ER beta receptors, thus stimulating ER-mediated luciferase induction in vitro. These data also suggest that in vivo metabolism of PBDEs may produce more potent pseudoestrogens.
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