3,5,3',5'-tetrachlorobiphenyl is a weak oestrogen agonist in vitro and in vivo.
Polychlorinated biphenyls (PCBs) are widespread, persistent environmental contaminants of which some congeners can act as endocrine disrupters. Previous work has shown that 3,4,3',4'-tetrachlorobiphenyl (PCB77) can act as an oestrogen with actions mediated through the oestrogen receptor. Here, oestrogenic actions have been assessed for two further tetrachlorobiphenyl isomers. Assays of oestrogenic action have involved (1) ligand regulation of oestrogen-sensitive gene expression; (2) ligand regulation of cell growth in oestrogen-dependent human breast cancer cell lines MCF7 McGrath and ZR-75-1; and (3) ligand activity in the immature mouse uterine weight bioassay in vivo. These results demonstrate that 3,5,3',5'-tetrachlorobiphenyl (PCB 80) can be considered to be a weak oestrogen agonist, but the 2,5,2',5'-congener (PCB 52) revealed no oestrogenic properties in any of these assays. Implications of these results are discussed in relation to structure-activity predictions for environmental oestrogens.
Nesaretnam
K
K
School of Animal and Microbial Sciences, The University of Reading, Whiteknights, UK.
Darbre
P
P
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D004785:Environmental Pollutants / Q000378:metabolism / Q000633:toxicity*; D004968:Estrogens, Non-Steroidal / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008024:Ligands; D051379:Mice; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D011078:Polychlorinated Biphenyls / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship; D014162:Transfection; D014407:Tumor Cells, Cultured; D014599:Uterus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D004785:Environmental Pollutants; D004968:Estrogens, Non-Steroidal; D008024:Ligands; D011960:Receptors, Estrogen; D011078:Polychlorinated Biphenyls; C029860:3,5,3',5'-tetrachlorobiphenyl