title: Effect of nonpersistent pesticides on estrogen receptor, androgen receptor, and aryl hydrocarbon receptor.
abstract: Nonpersistent pesticides are considered less harmful for the environment, but their impact as endocrine disruptors has not been fully explored. The pesticide Switch was applied to grape vines, and the maximum residue concentration of its active ingredients was quantified. The transactivation potential of the pesticides Acorit, Frupica, Steward, Reldan, Switch, Cantus, Teldor, and Scala and their active compounds (hexythiazox, mepanipyrim, indoxacarb, chlorpyrifos-methyl, cyprodinil, fludioxonil, boscalid, fenhexamid, and pyrimethanil) were tested on human estrogen receptor α (ERα), androgen receptor (AR) and arylhydrocarbon receptor (AhR) in vitro. Relative binding affinities of the pure pesticide constituents for AR and their effect on human breast cancer and prostate cancer cell lines were evaluated. Residue concentrations of Switch's ingredients were below maximum residue limits. Fludioxonil and fenhexamid were ERα agonists (EC50 -values of 3.7 and 9.0 μM, respectively) and had time-dependent effects on endogenous ERα-target gene expression (cyclin D1, progesterone receptor, and nuclear respiratory factor 1) in MCF-7 human breast cancer cells. Fludioxonil, mepanipyrim, cyprodinil, pyrimethanil, and chlorpyrifos-methyl were AhR-agonists (EC50 s of 0.42, 0.77, 1.4, 4.6, and 5.1 μM, respectively). Weak AR binding was shown for chlorpyrifos-methyl, cyprodinil, fenhexamid, and fludioxonil. Assuming a total uptake which does not take metabolism and clearance rates into account, our in vitro evidence suggests that pesticides could activate pathways affecting hormonal balance, even within permitted limits, thus potentially acting as endocrine disruptors.
authors: Christian Doppler Laboratory for Receptor Biotechnology, A-1190 Vienna, Austria; Department of Biotechnology, University of Natural Resources and Life Sciences Vienna, A-1190 Vienna, Austria.
authors: Svjetlana
authors: S
authors: Medjakovic
authors: Alfred
authors: A
authors: Zoechling
authors: Petra
authors: P
authors: Gerster
authors: Margarita M
authors: MM
authors: Ivanova
authors: Yun
authors: Y
authors: Teng
authors: Carolyn M
authors: CM
authors: Klinge
authors: Barbara
authors: B
authors: Schildberger
authors: Michael
authors: M
authors: Gartner
authors: Alois
authors: A
authors: Jungbauer
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism; D045744:Cell Line, Tumor; D052244:Endocrine Disruptors / Q000633:toxicity*; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D010575:Pesticides / Q000633:toxicity*; D011471:Prostatic Neoplasms / Q000378:metabolism; D011944:Receptors, Androgen / Q000378:metabolism*; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*
chemical_list: C410798:AR protein, human; C506487:ESR1 protein, human; D052244:Endocrine Disruptors; D047628:Estrogen Receptor alpha; D010575:Pesticides; D011944:Receptors, Androgen; D018336:Receptors, Aryl Hydrocarbon
keywords: androgen receptor; aryl hydrocarbon receptor; estrogen receptor; fenhexamid; fludioxonil; human cancer cell lines; pesticides; wine