Araki Naohiro, Ohno Ken, Nakai Makoto, Takeyoshi Masahiro, Iida Mitsuru
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.
Toxicol In Vitro. 2005 Sep;19(6):831-42. doi: 10.1016/j.tiv.2005.04.009.
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.
最近，工业化学品作为内分泌干扰物的潜在影响受到了极大关注。在本报告中，我们进行了一项初步研究，以验证AR-EcoScreen细胞用于雄激素受体（AR）激动剂和拮抗剂活性一级筛选的用途。从253种测试化合物中，我们鉴定出两种AR激动剂和九种拮抗剂。两种激动剂，2-叔丁基蒽醌和苯并蒽酮，相对较弱（分别在2.54x10(-7)和4.46x10(-6) M时，对阳性对照5α-二氢睾酮的最大激活率为10%）。最有效的拮抗剂是3,3'-二氯联苯胺二盐酸盐（IC50 = 2.28x10(-7) M）。抗雄激素活性的顺序为3,3'-二氯联苯胺二盐酸盐>4-二乙氨基苯甲醛>4,4'-[1-[4-[1-(4-羟基苯基)-1-甲基乙基]苯基]亚乙基]双[苯酚]>2,4,6-三氯苯肼 = 4-(苯丙基)吡啶>2-羟基-4-甲氧基二苯甲酮>2,2-双(4-氰基苯基)丙烷>4-甲氧基-2-甲基二苯胺 = 2,4-二苯基-4-甲基戊烯-1。这些结果表明，AR-EcoScreen细胞系有潜力用作大规模一级筛选化学品雄激素受体激动剂和拮抗剂活性的工具。
