title: Screening for androgen receptor activities in 253 industrial chemicals by in vitro reporter gene assays using AR-EcoScreen cells.
abstract: 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 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, 5alpha-dihydrotestosterone, at 2.54x10(-7) and 4.46x10(-6) M, respectively). The most potent antagonist was 3,3'-dichlorobenzidine dihydrochloride (IC50 = 2.28x10(-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-EcoScreen 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.
authors.affiliation: EcoScreen R&D Section, Endocrine Disrupting Chemical Analysis Center, Otsuka Life Science Initiative, Otsuka Pharmaceutical Co., Ltd., 224-18 Ebisuno Hiraishi, Kawauchi-cho, Tokushima 771-0195, Japan.
authors.forename: Naohiro
authors.initials: N
authors.lastname: Araki
authors.forename: Ken
authors.initials: K
authors.lastname: Ohno
authors.forename: Makoto
authors.initials: M
authors.lastname: Nakai
authors.forename: Masahiro
authors.initials: M
authors.lastname: Takeyoshi
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Iida
mesh_terms: D000726:Androgen Antagonists / Q000633:toxicity; D059002:Androgen Receptor Antagonists; D000728:Androgens; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D013196:Dihydrotestosterone / Q000378:metabolism; D004121:Dimethyl Sulfoxide; D017930:Genes, Reporter / Q000187:drug effects*; D005818:Genetic Engineering; D008156:Luciferases / Q000235:genetics; D008297:Male; D009930:Organic Chemicals / Q000633:toxicity*; D010865:Pilot Projects; D051381:Rats; D011944:Receptors, Androgen / Q000187:drug effects*; D015203:Reproducibility of Results; D045165:Testosterone Congeners / Q000494:pharmacology; D018675:Toxicity Tests; D014162:Transfection
chemical_list: D000726:Androgen Antagonists; D059002:Androgen Receptor Antagonists; D000728:Androgens; D009930:Organic Chemicals; D011944:Receptors, Androgen; D045165:Testosterone Congeners; D013196:Dihydrotestosterone; D008156:Luciferases; D004121:Dimethyl Sulfoxide