title: Effects of currently used pesticides and their mixtures on the function of thyroid hormone and aryl hydrocarbon receptor in cell culture.
abstract: Evidence suggest that exposure to pesticides can interfere with the endocrine system by multiple mechanisms. The endocrine disrupting potential of currently used pesticides in Denmark was analyzed as single compounds and in an equimolar mixture of 5 selected pesticides. The pesticides were previously analyzed for effects on the function of estrogen and androgen receptors, the aromatase enzyme and steroidogenesis in vitro. In this study, the effect on thyroid hormone (TH) function and aryl hydrocarbon receptor (AhR) transactivity was assessed using GH3 cell proliferation assay (T-screen) and AhR responsive luciferase reporter gene bioassay, respectively. Thirteen pesticides were analyzed as follows: 2-methyl-4-chlorophenoxyacetic acid, terbuthylazine, iodosulfuron-methyl-sodium, mesosulfuron-methyl, metsulfuron-methyl, chlormequat chloride, bitertanol, propiconazole, prothioconazole, mancozeb and its metabolite ethylene thiourea, cypermethrin, tau-fluvalinate, and malathion (currently banned in DK). In the T-screen, prothioconazole, malathion, tau-fluvalinate, cypermethrin, terbuthylazine and mancozeb significantly stimulated and bitertanol and propiconazole slightly reduced the GH3 cell proliferation. In the presence of triiodothyronine (T3), prothioconazole, tau-fluvalinate, propiconazole, cypermethrin and bitertanol significantly antagonized the T3-induced GH3 cell proliferation. Eleven of the tested pesticides agonized the AhR function, and bitertanol and prothioconazole inhibited the basal AhR activity. Bitertanol, propiconazole, prothioconazole and cypermethrin antagonized the TCDD-induced AhR transactivation at the highest tested concentration. The 5-component mixture had inducing effect but the combined effect could not be predicted due to the presence of bitertanol eliciting inhibitory effect. Upon removal of bitertanol from the mixture, the remaining four pesticides acted additively. In conclusion, our data suggest that pesticides currently used in Denmark can interfere with TH signaling and AhR function in vitro and might have the potential to cause endocrine disruption.
authors: Centre for Arctic Health & Unit of Cellular and Molecular Toxicology, Department of Public Health, Aarhus University, Aarhus, Denmark.
authors: Mandana
authors: M
authors: Ghisari
authors: Centre for Arctic Health & Unit of Cellular and Molecular Toxicology, Department of Public Health, Aarhus University, Aarhus, Denmark.
authors: Manhai
authors: M
authors: Long
authors: Centre for Arctic Health & Unit of Cellular and Molecular Toxicology, Department of Public Health, Aarhus University, Aarhus, Denmark.
authors: Agnese
authors: A
authors: Tabbo
authors: Centre for Arctic Health & Unit of Cellular and Molecular Toxicology, Department of Public Health, Aarhus University, Aarhus, Denmark. Electronic address: ebj@mil.au.dk.
authors: Eva Cecilie
authors: EC
authors: Bonefeld-Jørgensen
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003718:Denmark; D004305:Dose-Response Relationship, Drug; D052244:Endocrine Disruptors / Q000633:toxicity*; D017930:Genes, Reporter; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D010575:Pesticides / Q000633:toxicity*; D051381:Rats; D018336:Receptors, Aryl Hydrocarbon / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D018570:Risk Assessment; D015398:Signal Transduction / Q000187:drug effects; D013961:Thyroid Gland / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D014162:Transfection; D014284:Triiodothyronine / Q000378:metabolism*
chemical_list: D052244:Endocrine Disruptors; D010575:Pesticides; D018336:Receptors, Aryl Hydrocarbon; D014284:Triiodothyronine
keywords: Aryl hydrocarbon receptor; Endocrine disruption; Pesticide; T-Screen; Thyroid hormone