Screening for androgen receptor activities in 253 industrial chemicals by in vitro reporter gene assays using AR-EcoScreen™ 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-EcoScreen (TM) cells for tier I 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, 5 alpha-dihydrotestosterone, at 2.54 x 10(-7) and 4.46 x 10(-6) M, respectively). The most potent antagonist was 3,3'-dichlorobenzidine dihydrochloride (IC50 = 2.28 x 10(-7) M). The order of the anti-androgenic activities was 3,3'-dichlorobenzidine dihydrochloride > 4-diethylamino-benzaldehyde > 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-EcoScreen (TM) cell line has the potential to be used as a tool for the large scale tier I screening of chemicals for androgen receptor agonist and antagonist activity. (c) 2005 Elsevier Ltd. All rights reserved.