Effects of currently used pesticides in assays for estrogenicity, androgenicity, and aromatase activity in vitro.
Twenty-four pesticides were tested for interactions with the estrogen receptor (ER) and the androgen receptor (AR) in transactivation assays. Estrogen-like effects on MCF-7 cell proliferation and effects on CYP19 aromatase activity in human placental microsomes were also investigated. Pesticides (endosulfan, methiocarb, methomyl, pirimicarb, propamocarb, deltamethrin, fenpropathrin, dimethoate, chlorpyriphos, dichlorvos, tolchlofos-methyl, vinclozolin, iprodion, fenarimol, prochloraz, fosetyl-aluminum, chlorothalonil, daminozid, paclobutrazol, chlormequat chlorid, and ethephon) were selected according to their frequent use in Danish greenhouses. In addition, the metabolite mercaptodimethur sulfoxide, the herbicide tribenuron-methyl, and the organochlorine dieldrin, were included. Several of the pesticides, dieldrin, endosulfan, methiocarb, and fenarimol, acted both as estrogen agonists and androgen antagonists. Prochloraz reacted as both an estrogen and an androgen antagonist. Furthermore, fenarimol and prochloraz were potent aromatase inhibitors while endosulfan was a weak inhibitor. Hence, these three pesticides possess at least three different ways to potentially disturb sex hormone actions. In addition, chlorpyrifos, deltamethrin, tolclofos-methyl, and tribenuron-methyl induced weak responses in one or both estrogenicity assays. Upon cotreatment with 17beta-estradiol, the response was potentiated by endosulfan in the proliferation assay and by pirimicarb, propamocarb, and daminozid in the ER transactivation assay. Vinclozolin reacted as a potent AR antagonist and dichlorvos as a very weak one. Methomyl, pirimicarb, propamocarb, and iprodion weakly stimulated aromatase activity. Although the potencies of the pesticides to react as hormone agonists or antagonists are low compared to the natural ligands, the integrated response in the organism might be amplified by the ability of the pesticides to act via several mechanism and the frequent simultaneous exposure to several pesticides.
Andersen
Helle Raun
HR
Environmental Medicine, Institute of Public Health, University of Southern Denmark, Odense, Winsløwparken 17, DK-5000 Odense C, Denmark.
Vinggaard
Anne Marie
AM
Rasmussen
Thomas Hoj
TH
Gjermandsen
Irene Marianne
IM
Bonefeld-Jørgensen
Eva Cecilie
EC
D000818:Animals; D047072:Aromatase Inhibitors; D001681:Biological Assay; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D016466:CHO Cells; D002455:Cell Division / Q000187:drug effects; D006224:Cricetinae; D004791:Enzyme Inhibitors / Q000633:toxicity*; D045166:Estradiol Congeners / Q000633:toxicity*; D005260:Female; D006801:Humans; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology; D010575:Pesticides / Q000633:toxicity*; D010920:Placenta / Q000187:drug effects / Q000201:enzymology; D011247:Pregnancy; D011944:Receptors, Androgen / Q000187:drug effects; D011960:Receptors, Estrogen / Q000187:drug effects; D045165:Testosterone Congeners / Q000633:toxicity*; D015533:Transcriptional Activation / Q000187:drug effects; D014407:Tumor Cells, Cultured
D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D045166:Estradiol Congeners; D010575:Pesticides; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D045165:Testosterone Congeners