Six high-priority organochlorine pesticides, either singly or in combination, are nonestrogenic in transfected HeLa cells.
There have been increasing concerns that environmental chemicals may adversely affect the health of humans and wildlife by acting as endocrine modulators. These concerns have been augmented by the realization that human exposure occurs not just to single chemical agents, but typically to mixtures of chemicals that could exhibit estrogenic activity qualitatively and/or quantitatively different from that of individual components. To address these concerns, we have evaluated the ability of six organochlorine pesticides (4, 4'-DDT, 4,4'-DDD, 4,4'-DDE, aldrin, dieldrin, or endrin, all classified high priority by ATSDR) to modulate transcriptional activation of an estrogen-responsive reporter gene in transfected HeLa cells. In these assays, HeLa cells cotransfected with an expression vector encoding estrogen receptor and an estrogen-responsive chloramphenicol acetyltransferase (CAT) reporter plasmid were exposed to these pesticides individually and in defined combinations. While estradiol consistently elicited 10- to 23-fold dose-dependent inductions in these assays, the six organochlorine pesticides showed no detectable dose-related response when tested individually. When tested in binary combinations, the pesticide mixtures showed no additional estrogenicity. Thus, the pesticides tested, singly or as mixtures, showed virtually no evidence of estrogenicity.
Tully
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DB
Laboratory of Toxicology, Environmental Toxicology Program, National Institute of Environmental Health Sciences, 111 TW Alexander Drive, Bldg. 101, Room E-145, Research Triangle Park, NC 27709-2233, USA. dtully@mindspring.com
Cox
V T
VT
Mumtaz
M M
MM
Davis
V L
VL
Chapin
R E
RE
D000452:Aldrin / Q000494:pharmacology; D003634:DDT / Q000494:pharmacology; D003633:Dichlorodiphenyl Dichloroethylene / Q000494:pharmacology; D003632:Dichlorodiphenyldichloroethane / Q000494:pharmacology; D004026:Dieldrin / Q000494:pharmacology; D004357:Drug Synergism; D004732:Endrin / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology*; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D017930:Genes, Reporter; D006367:HeLa Cells / Q000187:drug effects; D006801:Humans; D007306:Insecticides / Q000494:pharmacology*; D011960:Receptors, Estrogen / Q000187:drug effects / Q000235:genetics; D014162:Transfection
D004965:Estrogen Antagonists; D004968:Estrogens, Non-Steroidal; D007306:Insecticides; D011960:Receptors, Estrogen; D003633:Dichlorodiphenyl Dichloroethylene; D004958:Estradiol; D003634:DDT; D004026:Dieldrin; D004732:Endrin; D000452:Aldrin; D003632:Dichlorodiphenyldichloroethane