Screening for androgen receptor activities in 253 industrial chemicals by in vitro reporter gene assays using AR-EcoScreenTM cells

Recently, there has been great concern about the potential of industrial chemicals to act as endocrine disrupters. In this report, we conducted a pilot study to validate the use of AR-EcoScreenTM cells for tier 1 screening of androgen receptor (AR) agonist and antagonist activities. From 253 test compounds, we identified two AR agonists and nine antagonists. The two agonists, 2-tert-butylanthraquinone and benzoanthrone, were relatively weak (10% maximal activation of the positive control, 5α-dihydrotestosterone, at 2.54 × 10−7 and 4.46 × 10−6 M, respectively). The most potent antagonist was 3,3′-dichlorobenzidine dihydrochloride (IC50 = 2.28 × 10−7 M). The order of the anti-androgenic activities was 3,3′-dichlorobenzidine dihydrochloride > 4-diethylaminobenzaldehyde > 4,4′-[1-[4-[1-(4-hydroxyphenyl)-1-methylethyl]phenyl]ethylidene]bis[phenol] > 2,4,6-trichlorophenylhydrazine = 4-(phenylpropyl)pyridine > 2-hydroxy-4-methoxybenzophenone > 2,2-bis(4-cyanophenyl)propane > 4-methoxy-2-methyldiphenylamine = 2,4-diphenyl-4-methylpentene-1. These results suggest that AR-EcoScreenTM cell line has the potential to be used as a tool for the large scale tier 1 screening of chemicals for androgen receptor agonist and antagonist activity.