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2,2',6,6'‐tetrachlorobiphenyl is estrogenic in vitro and in vivo
Author(s) -
Arcaro Kathleen F.,
Yi Liangdong,
Seegal Richard F.,
Vakharia Dilip D.,
Yang Yi,
Spink David C.,
Brosch Karl,
Gierthy John F.
Publication year - 1999
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/(sici)1097-4644(19990101)72:1<94::aid-jcb10>3.0.co;2-y
Subject(s) - metabolite , in vivo , chemistry , in vitro , estrogen receptor , chlorine , estrogen , medicine , chlorine atom , antagonist , receptor , pharmacology , endocrinology , biochemistry , biology , medicinal chemistry , genetics , organic chemistry , cancer , breast cancer
Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants whose effects on biological systems depend on the number of and the positions of the chlorine substitutions. In the present study we examined the estrogenicity of the fully ortho ‐substituted PCB, 2,2',6,6'‐tetrachlorobiphenyl (2,2',6,6'‐TeCB). This PCB was chosen as the prototypical ortho ‐substituted PCB to test the hypothesis that ortho ‐substitution of a PCB with no para ‐ or meta ‐chlorine‐substitutions results in enhanced estrogenic activity. The results indicate that 2,2',6,6'‐TeCB 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 μM 2,2',6,6'‐TeCB to the medium of MCF‐7 cultures was inhibited by the estrogen receptor (ER) antagonist, LY156758, suggesting that 2,2',6,6'‐TeCB or a metabolite is acting through an ER‐dependent mechanism. Results from competitive binding assays using recombinant human (rh) ER indicate that 2,2',6,6'‐TeCB does not bind rhERα or rhERβ. A metabolite of 2,2',6,6'‐TeCB, 2,2',6,6'‐tetrachloro‐4‐biphenylol (4‐OH‐2,6,2',6'‐TCB), does bind rhERα and rhERβ and is also 10‐fold more estrogenic than 2,2',6,6'‐TeCB in the MCF‐7 focus assay; however, this metabolite is not detected in the medium of MCF‐7 cultures exposed to 2,2',6,6'‐TeCB. Taken together, the results suggest that the estrogenicity observed in human breast cancer cells 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. © 1999 Wiley‐Liss, Inc.