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Hydroxylated Polychlorinated Biphenyl Metabolites Are Anti-estrogenic in a Stably Transfected Human Breast Adenocarcinoma (MCF7) Cell Line

1997; Elsevier BV; Volume: 144; Issue: 2 Linguagem: Inglês

10.1006/taap.1997.8163

1096-0333

Vincent J. Kramer, William G. Helferich, Åke Bergman, Eva Klasson‐Wehler, John P. Giesy,

Environmental Toxicology and Ecotoxicology

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 anin vitrobioassay 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 17β-estradiol (E2), comparing the concentration–response curves using charcoal-stripped medium (0.0009 nmE2), and two physiologically relevant E2 concentrations (0.1 and 1.0 nmE2). 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 samples. The remaining OHCBs exhibited "anti-estrogenicity" that was related to their effect on cell viability and, therefore, cannot be described as exhibiting "hormone disruption" solely by an estrogen receptor mediated mechanism. OHCB anti-estrogenic activity was eliminated in the presence of E2 concentrations normally found in humans, except for 4,4′-(OH)2-3,3′,5,5′-Cl4-biphenyl. 4-OH-2′,3′,4′,5′-Cl4-biphenyl and 4-OH-2′,4′,6′-Cl3-biphenyl were partial estrogen agonists, exhibiting weak estrogenicity in the presence of 0.0009 nmE2 and weak anti-estrogenicity in the presence of 0.1 and 1 nmE2. Human metabolites of PCBs were not estrogenic in MCF7 cells.