Synergistic activation of estrogen receptor with combinations of environmental chemicals.
Certain chemicals in the environment are estrogenic. The low potencies of these compounds, when studied singly, suggest that they may have little effect on biological systems. The estrogenic potencies of combinations of such chemicals were screened in a simple yeast estrogen system (YES) containing human estrogen receptor (hER). Combinations of two weak environmental estrogens, such as dieldrin, endosulfan, or toxaphene, were 1000 times as potent in hER-mediated transactivation as any chemical alone. Hydroxylated polychlorinated biphenyls shown previously to synergistically alter sexual development in turtles also synergized in the YES. The synergistic interaction of chemical mixtures with the estrogen receptor may have profound environmental implications. These results may represent a previously uncharacterized level of regulation of estrogen-associated responses.
Arnold
S F
SF
Department of Environmental Health Sciences, Tulane University of Public Health and Tropical Medicine, New Orleans, LA 70112, USA.
Klotz
D M
DM
Collins
B M
BM
Vonier
P M
PM
Guillette
L J
LJ
McLachlan
J A
JA
D001667:Binding, Competitive; D002706:Chlordan / Q000378:metabolism / Q000494:pharmacology; D004026:Dieldrin / Q000378:metabolism / Q000494:pharmacology; D004357:Drug Synergism; D004726:Endosulfan / Q000378:metabolism / Q000494:pharmacology; D004785:Environmental Pollutants / Q000378:metabolism / Q000494:pharmacology*; D004958:Estradiol / Q000378:metabolism; D004968:Estrogens, Non-Steroidal / Q000378:metabolism / Q000494:pharmacology*; D017930:Genes, Reporter; D006801:Humans; D007306:Insecticides / Q000378:metabolism / Q000494:pharmacology*; D011078:Polychlorinated Biphenyls / Q000494:pharmacology*; D011960:Receptors, Estrogen / Q000187:drug effects* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics; D014112:Toxaphene / Q000378:metabolism / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D004785:Environmental Pollutants; D004968:Estrogens, Non-Steroidal; D007306:Insecticides; D011960:Receptors, Estrogen; D002706:Chlordan; D004958:Estradiol; D014112:Toxaphene; D011078:Polychlorinated Biphenyls; D004026:Dieldrin; D004726:Endosulfan