Anti-androgenic activities of environmental pesticides in the MDA-kb2 reporter cell line.
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, organochlorine, 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 h 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.
Aït-Aïssa
S
S
Unité d'Ecotoxicologie in vitro et in vivo, Institut National de l'Environnement Industriel et des Risques (INERIS), BP 2, F-60550 Verneuil-en-Halatte, France. selim.ait-aissa@ineris.fr
Laskowski
S
S
Laville
N
N
Porcher
J-M
JM
Brion
F
F
D059002:Androgen Receptor Antagonists / Q000008:administration & dosage / Q000633:toxicity*; D045744:Cell Line, Tumor; D013196:Dihydrotestosterone / Q000633:toxicity; D052244:Endocrine Disruptors / Q000008:administration & dosage / Q000633:toxicity*; D017930:Genes, Reporter / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D010575:Pesticides / Q000633:toxicity*; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects
D059002:Androgen Receptor Antagonists; D052244:Endocrine Disruptors; D010575:Pesticides; D013196:Dihydrotestosterone