Activation of alpha- and beta-estrogen receptors by persistent pesticides in reporter cell lines.
Many persistent pesticides have been implicated in reproductive and developmental adverse effects, in man and wildlife. It has been hypothesized that these so-called xeno-hormones could upset the endocrine system function by binding to human estrogen receptor alpha and beta (ERalpha, beta) and thus be responsible for the higher incidence of breast and cervical cancer, infertility and endometriosis. In this report, forty-nine pesticides were tested for ERalpha and beta activation or inhibition in stable reporter cell lines, HELN ERalpha and ERbeta. Stable transfection of the ERalpha and ERbeta constructs together with an estrogen reporter luciferase vector into the HeLa cell line resulted in two estradiol-sensitive cell lines. In our model, fifteen of the tested pesticides were found to agonize the ERalpha-mediated transcription in a dose-dependent manner and DDT, trans-nonachlor, chlordane, fenvalerate and toxaphene were also capable to activate ERbeta. Antagonistic activities toward hERalpha and hERbeta were shown in three (carbaryl, pentachlorophenol and 2,4,5-trichlorophenoxyacetic acid) and seven (chlordecone, methoxychlor, carbaryl, endosulfan, endrin, dieldrin, aldrin) pesticides, respectively. Remarkably chlordecone and methoxychlor which were the most effective antagonist compounds for hERbeta, were agonists for hERalpha. Although the ERalpha activation potential of the pesticides was lower than that of estradiol, the overall body scale response might be amplified by the ability of pesticides to act via several mechanisms and by frequent and prolonged exposure to different pesticides, even at low concentrations.
Lemaire
Géraldine
G
Laboratoire de Toxicologie Cellulaire, Moléculaire et Génomique, INRA, UMR 1112 ROSE, B.P. 167, 400 route des Chappes 06903 Sophia Antipolis, France.
Mnif
Wissem
W
Mauvais
Pascale
P
Balaguer
Patrick
P
Rahmani
Roger
R
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D016466:CHO Cells; D002460:Cell Line; D007631:Chlordecone / Q000494:pharmacology; D006224:Cricetinae; D004958:Estradiol / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000187:drug effects* / Q000235:genetics; D047629:Estrogen Receptor beta / Q000187:drug effects* / Q000235:genetics; D004967:Estrogens; D015870:Gene Expression / Q000187:drug effects; D017930:Genes, Reporter / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D008731:Methoxychlor / Q000494:pharmacology; D010573:Pesticide Residues / Q000494:pharmacology; D010575:Pesticides / Q000494:pharmacology*; D010957:Plasmids / Q000235:genetics; D013778:Tetrazolium Salts; D013844:Thiazoles; D014162:Transfection
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D010573:Pesticide Residues; D010575:Pesticides; D013778:Tetrazolium Salts; D013844:Thiazoles; D004958:Estradiol; C022616:thiazolyl blue; D007631:Chlordecone; D008731:Methoxychlor