Anti-androgenic activities of environmental pesticides in the MDA-kb2 reporter cell line

Abstract

Pesticides have been suspected to act as endocrine disruptive compounds (EDCs) through several mechanisms of action, however data are still needed for a number of currently used pesticides. In the present study, 30 environmental pesticides selected from different chemical classes (azole, carbamate, dicarboximide, oganochlorine, organophosphorus, oxadiazole, phenylureas, pyrazole, pyrimidine, pyrethroid and sulfonylureas) were tested for their ability to alter in vitro the transcriptional activity of the androgen receptor in the MDA-kb2 reporter cell line. The responsiveness of the system was checked by using a panel of reference ligands of androgen and glucocorticoid receptors. When tested alone at concentrations up to 10 µM, none of the studied pesticides were able to induce the reporter gene after a 18 hour exposure.Conversely, co-exposure experiments with 0.1 nM dihydrotestosterone (DHT) allowed identifying 15 active pesticides with IC 50 ranging from 0.2 µM for vinclozolin to 12 µM for fenarimol. Fipronil and bupirimate were here newly described for their AR antagonistic activity.

QSAR Model for Androgen Receptor Antagonism - Data from CHO Cell Reporter Gene Assays

“…This disagreement for chlordane was also reported previously by Aït-Aïssa et al [34]. For chemicals showing AR antagonism in MDA cells but inactive in CHO cells, all were non-steroids (phenanthrene, pirimiphosmethyl, chlorpropham, metolachlor, pretilachlor) [2,4,28,34,55]. Chemicals like diethyl phthalate, aldrin and γ-lindane having IC 50 values at concentrations of 60 -80 μM in MDA cells were negative in CHO cells [4,28,40] where the cut-off for positive results was set at 10 μM.…”

“…The fourth chemical was chlordane [2,34,54]. This disagreement for chlordane was also reported previously by Aït-Aïssa et al [34]. For chemicals showing AR antagonism in MDA cells but inactive in CHO cells, all were non-steroids (phenanthrene, pirimiphosmethyl, chlorpropham, metolachlor, pretilachlor) [2,4,28,34,55].…”

“…chemicals with AR antagonism in CHO cells were inactive in MDA cells with steroids dominating, making up three (progesterone, cyproterone acetate and 17β-estradiol) out of four chemicals [4,28,53]. The fourth chemical was chlordane [2,34,54]. This disagreement for chlordane was also reported previously by Aït-Aïssa et al [34].…”

“…Chinese hamster ovary (CHO-K1) cells [4], human mammary carcinoma cells (MDA-kb2) [28], U2 OS cells [29], African monkey kidney cells (CV-1) [30], human prostate adenocarcinoma PC-3 derived cell line (PALM) [31], human hepatoma liver cells (HepG2) [32] and yeast [33]. However, discrepancies between data from the different in vitro cell assays have been reported [34,35]. Previously it has been described that effectors which interact with the ligandreceptor complex, like response elements, corepressor or coactivator proteins, or other transcription factors, are cell-type dependent [36].…”

Environmental (anti-)androgenic chemicals affect germinal vesicle breakdown (GVBD) of Xenopus laevis oocytes in vitro

“…Several fungicides, such as vinclozolin, procymidone, and prochloraz, are well-known AR antagonists (Aït-Aïssa et al, 2010;Kolle et al, 2011;Wilson et al, 2008). Methoxychlor was shown to have a very weak ARantagonistic activity (Maness et al, 1998).…”