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Toxicol Lett. 2006 Jan 5;160(2):151-7. Epub 2005 Aug 25.

Androgen receptor activities of p,p'-DDE, fenvalerate and phoxim detected by androgen receptor reporter gene assay.

Author information

1
The Key Laboratory of Reproductive Medicine of Jiangsu Province, Institute of Toxicology, Nanjing Medical University, Jiangsu, PR China.

Abstract

In this study, we have developed a transient human androgen receptor (hAR) reporter gene assay using African monkey kidney cell line CV-1. The assay displayed appropriate response to the known androgen receptor (AR) agonist 5alpha-dihydrotestosterone (DHT) and AR antagonist nilutamide. DHT induced AR-mediated transcriptional activity in a concentration-dependent manner with median effective concentration (EC(50)) value of 3.90 x 10(-10) M. Nilutamide exhibited potent antiandrogenic activity with median inhibitory concentration (IC(50)) value of 8.90 x 10(-7) M. The transcription could not be activated by glucocorticoid receptor (GR) agonist dexamethasone, which suggested that the assay system be highly specific to androgenic compounds without cross-talk to GR agonist. The assay shows acceptable repeatability to DHT with intra coefficient of variability (CV) of 9.3% and inter CV of 10.9%. We applied this assay to evaluate the androgenic and antiandrogenic activities of some pesticides including organochlorine p,p'-dichlorodiphenyldichloroethylene (DDE), pyrethroid fenvalerate and organophosphorus phoxim. The results showed that p,p'-DDE exhibited potent antiandrogenic activity. Fenvalerate acted as weak AR antagonist and phoxim did not show AR antagonistic activity. We failed to find AR agonistic effects of the three pesticides. The present study provided a promising tool to screen for AR agonists and antagonists.

PMID:
16125883
DOI:
10.1016/j.toxlet.2005.06.016
[Indexed for MEDLINE]

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