2,2',6,6'-tetrachlorobiphenyl is
estrogenic in vitro and in vivo
Journal of Cellular Biochemistry Volume 72, Issue 1, 1999. Pages:
94-102
Article Abstract
Kathleen F. Arcaro 1 2, Liangdong Yi 1, Richard F. Seegal 1 2, Dilip D. Vakharia 2, Yi Yang 2, David C. Spink 1 2, Karl Brosch 2, John F. Gierthy 1 2 * 1School of Public Health, State University of New York at Albany, Albany, New York 12222 2Wadsworth Center, New York State Department of Health, Albany, New York 12201
email: John F. Gierthy (gierthy@wadsworth.org)
*Correspondence to John F. Gierthy, Wadsworth Laboratories, New York State Department of Health, Empire State Plaza, Albany, NY 12201. Funded by: NIEHS Superfund Basic Research Program; Grant Number: P42 ES04913 Keywords polychlorinated biphenyls; endocrine disruptors; MCF-7 cells
Abstract 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 M 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 rhER or rhER. A metabolite of 2,2',6,6'-TeCB, 2,2',6,6'-tetrachloro-4-biphenylol (4-OH-2,6,2',6'-TCB), does bind rhER and rhER 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.
Received: 16 July 1998; Accepted: 17 July 1998
