HYDROXYLATED POLYCHLORINATED BIPHENYL METABOLITES ARE ANTIESTROGENIC IN A STABLY TRANSFECTED HUMAN BREAST ADENOCARCINOMA (MCF7) CELL-LINE

Hydroxylated metabolites of polychlorinated biphenyls (OHCBs) have bee n 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 inhi bition of vitamin A and thyroxin transport, estrogenicity in a mouse u terotrophic assay, and feminization of male turtle sexual development. OHCBs, representing both environmentally derived and laboratory expos ure-derived metabolites, were tested in an in vitro bioassay utilizing an estrogen-responsive human breast adenocarcinoma cell line (MCF7-LU C) stably transfected with a luciferase reporter gene linked to estrog en responsive elements. OHCB activity was tested at three different me dia concentrations of 17 beta-estradiol (E2), comparing the concentrat ion-response curves using charcoal-stripped medium (0.0009 nM E2), and two physiologically relevant E2 concentrations (0.1 and 1.0 nM E2). E leven of 13 OHCBs tested were anti-estrogenic. Evidence for an estroge n receptor mediated mechanism of action was apparent for only two OHCB s-4-(OH)(2),3,3',4',5,5'- Cl-6-biphenyl and 4,4'-(OH)2-3,3',5,5 '-Cl-4 -biphenyl. These two have not been identified in environmental samples . The remaining OHCBs exhibited ''anti-estrogenicity '' that was relat ed to their effect on cell, viability and, therefore, cannot be descri bed as exhibiting ''hormone disruption'' solely by an estrogen recepto r 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'-Cl-3-biphenyl. 4-OH-2',3',4',5'-Cl-4-biphenyl an d 4-OH-2',4',6'-Cl-3-biphenyl were partial estrogen agonists, exhibiti ng weak estrogenicity in the presence of 0.0009 nM E2 and weak anti-es trogenicity in the presence of 0.1 and 1 nM E2. Human metabolites of P CBs were not estrogenic in MCF7 cells. (C) 1997 Academic Press.