Hydroxylated polychlorinated biphenyl metabolites are anti-estrogenic in a stably transfected human breast adenocarcinoma (MCF7) cell line

Toxicology and Applied Pharmacology
V J KramerJohn P Giesy

Abstract

Hydroxylated metabolites of polychlorinated biphenyls (OHCBs) have been identified in blood of marine mammals, fish-eating birds, and humans at concentrations in some cases exceeding those of the unmetabolized polychlorinated biphenyls (PCBs). OHCBs have been associated with inhibition of vitamin A and thyroxin transport, estrogenicity in a mouse uterotrophic assay, and feminization of male turtle sexual development. OHCBs, representing both environmentally derived and laboratory exposure-derived metabolites, were tested in an in vitro bioassay utilizing an estrogen-responsive human breast adenocarcinoma cell line (MCF7-LUC) stably transfected with a luciferase reporter gene linked to estrogen responsive elements. OHCB activity was tested at three different media concentrations of 17beta-estradiol (E2), comparing the concentration-response curves using charcoal-stripped medium (0.0009 nM E2), and two physiologically relevant E2 concentrations (0.1 and 1.0 nM E2). Eleven of 13 OHCBs tested were anti-estrogenic. Evidence for an estrogen receptor mediated mechanism of action was apparent for only two OHCBs-4-OH-2',3,3',4',5,5'-Cl6-biphenyl and 4,4'-(OH)2-3,3',5,5'-Cl4-biphenyl. These two have not been identified in environmental s...Continue Reading

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