2,2',6,6'-TETRACHLOROBIPHENYL IS ESTROGENIC IN-VITRO AND IN-VIVO

Citation
Kf. Arcaro et al., 2,2',6,6'-TETRACHLOROBIPHENYL IS ESTROGENIC IN-VITRO AND IN-VIVO, Journal of cellular biochemistry, 72(1), 1999, pp. 94-102
Citations number
38
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biology,"Cell Biology
ISSN journal
0730-2312
Volume
72
Issue
1
Year of publication
1999
Pages
94 - 102
Database
ISI
SICI code
0730-2312(1999)72:1<94:2IEIAI>2.0.ZU;2-5
Abstract
Polychlorinated biphenyls (PCBs) are ubiquitous Environmental contamin ants whose effects on biological systems depend on the number of and t he positions of the chlorine substitutions. In the present study we ex amined the estrogenicity of the fully ortho-substituted PCB, 2,2',6,6' -tetrachlorobiphenyl (2,2',6,6'-TeCB). This PCB was chosen as the prot otypical ortho-substituted PCB to test the hypothesis that ortho-subst itution of a PCB with no para- or meta-chlorine-substitutions results in enhanced estrogenic activity. The results indicate that 2,2',6,6'-T eCB is estrogenic both in vitro, in the MCF-7 cell focus assay, and in vivo, in the rat uterotropic assay. The estrogenic activity elicited by the addition of 5 mu M 2,2',6,6'-TeCB to the medium of MCF-7 cultur es was inhibited by the estrogen receptor (ER) antagonist, LY156758, s uggesting that 2,2',6,6'-TeCB or a metabolite is acting through an ER- dependent mechanism. Results from competitive binding assays using rec ombinant human (rh) ER indicate that 2,2',6,6'-TeCB does not bind rhER alpha or rhER beta. A metabolite of 2,2',6,6'-TeCB, 2,2',6,6'-tetrach loro-4-biphenylol (4-OH-2,6,2',6'-TCB), does bind rhER alpha and rhER beta and is also 10-fold more estrogenic than 2,2',6,6'-TeCB in the MC F-7 focus assay; however, this metabolite is not detected in the mediu m of MCF-7: cultures exposed to 2,2',6,6'-TeCB. Taken together, the re sults suggest that the estrogenicity observed in human breast cancer c ells and the rat uterus may be due to 1)an undetected metabolite of 2, 2',6,6'-TeCB binding to the ER, 2) 2,2',6,6'-TeCB binding directly to a novel form of the ER, or 3) an unknown mechanism involving the ER. J . Cell. Biochem. 72:94-102, 1999. (C) 1999 Wiley-Liss, Inc.