Antiestrogenic activity of hydroxylated polychlorinated biphenyl congeners identified in human serum

M. Moore, M. Mustain, K. Daniel, I. Chen, S. Safe, T. Zacharewski, B. Gillesby, A. Joyeux, P. Balaguer

Research output: Contribution to journalArticlepeer-review

142 Scopus citations


Several hydroxylated polychlorinated biphenyls (PCBs) identified in human serum have been synthesized and these include 2,2',3,4',5,5'-hexachloro-4-biphenylol; 2,3,3',4',5-pentachloro-4-biphenylol; 2',3,3',4',5-pentachloro-4-biphenylol; 2,2',3,3',4',5-hexachloro-4-biphenylol; 2,2',3,3',4',5,5'-heptachloro-4-biphenylol; 2,2',3,4',5,5',6-heptachloro-4-biphenylol; and 2,2',3',4,4',5,5'-heptachloro-3-biphenylol. The hydroxy-PCBs exhibited minimal binding to the rat uterine cytosolic estrogen receptor (ER) and did not induce proliferation of estrogen-responsive MCF-7 human breast cancer cells at concentrations ranging from 10-5 to 10-8 M. The estrogenic activity of these compounds was further investigated utilizing two estrogen-responsive in vitro bioassays, namely, (i) HeLa cells stably transfected with a Gal4:human ER chimera and a 17-mer-regulated luciferase reporter gene, and (ii) MCF-7 cells transiently transfected with a full-length human ER expression plasmid and a plasmid containing an estrogen-responsive vitellogenin A2 promoter linked to a chloramphenicol acetyl transferase (CAT) reporter gene. None of the hydroxy-PCBs significantly induced luciferase activity in the stably transfected HeLa cells or CAT activity in MCF-7 cells at concentrations as high as 10-5 M. The antiestrogenic effects of the hydroxy-PCBs were also investigated using the same bioassays in which the cells were co-treated with 17β-estradiol plus the hydroxy-PCBs. All of the hydroxy-PCB congeners inhibited one or more estrogenic response, and one congener, 2,2',3,4',5,5',6-heptachloro-4-biphenylol, inhibited 17β-estradiol-induced cell proliferation and CAT activity in MCF-7 cells and luciferase activity in HeLa cells.

Original languageEnglish (US)
Pages (from-to)160-168
Number of pages9
JournalToxicology and Applied Pharmacology
Issue number1
StatePublished - Jan 1997

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology


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