Antiestrogenic Activity of Hydroxylated Polychlorinated Biphenyl Congeners Identified in Human Serum
Identifieur interne : 000323 ( France/Analysis ); précédent : 000322; suivant : 000324Antiestrogenic Activity of Hydroxylated Polychlorinated Biphenyl Congeners Identified in Human Serum
Auteurs : M. Moore ; M. Mustain ; K. Daniel ; I. Chen ; S. Safe ; T. Zacharewski [Canada] ; B. Gillesby [Canada] ; A. Joyeux [France] ; P. Balaguer [France]Source :
- Toxicology and Applied Pharmacology [ 0041-008X ] ; 1997.
Abstract
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 10−5to 10−8m. The estrogenic activity of these compounds was further investigated utilizing two estrogen-responsivein vitrobioassays, 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 10−5m. The antiestrogenic effects of the hydroxy-PCBs were also investigated using the same bioassays in which the cells were cotreated 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.
Url:
DOI: 10.1006/taap.1996.8022
Affiliations:
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ISTEX:682AFC3A0887998752858FB7ABB7F999EB507127Le document en format XML
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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 10−5to 10−8m. The estrogenic activity of these compounds was further investigated utilizing two estrogen-responsivein vitrobioassays, 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 10−5m. The antiestrogenic effects of the hydroxy-PCBs were also investigated using the same bioassays in which the cells were cotreated 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.</div></front></TEI><affiliations><list><country><li>Canada</li><li>France</li></country><region><li>Languedoc-Roussillon</li><li>Occitanie (région administrative)</li></region><settlement><li>Montpellier</li></settlement></list><tree><noCountry><name sortKey="Chen, I" sort="Chen, I" uniqKey="Chen I" first="I." last="Chen">I. Chen</name><name sortKey="Daniel, K" sort="Daniel, K" uniqKey="Daniel K" first="K." last="Daniel">K. Daniel</name><name sortKey="Moore, M" sort="Moore, M" uniqKey="Moore M" first="M." last="Moore">M. 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