Abstract：
Estrogen receptor (ER) and androgen receptor (AR) transactivation assays for the benzophenone compounds (BPs) were performed using hERα-HeLa-9903 cells for ER and MMTV/22Rv1_GR-KO cells for AR. Results showed that some BPs, such as BP-1, BP-2, 4OH-BP, 4DHB, and 4-MBP, showed agonistic activity on ER with a higher RPCmax than 1 nM 17-β estradiol. The other BPs (BP, BP-3, BP-6, BP-7, and BP-8) showed low RPCmax in accordance with the OECD Test guideline (TG) 455 criteria, with BP-4 as the only ER-negative. However, the potency of the BPs was at least 1000 times less than the reference chemical, 17-β-estradiol. None of the BPs exhibited agonistic activity on AR except BP-2 which showed a small increase in activity. For further evaluation of the estrogenic effect of BPs based on the integrated approaches to testing and assessment (IATA) approach, existing data on ER binding, steroidogenesis, MCF-7 cell proliferation, and in vivo uterotrophic assays were collected and evaluated. There seemed to be a close association between the in vitro data on BPs, especially ER transcriptional activity, and the in vivo results of increased uterine weight. This case study implied that integrated approaches using in vitro data can be a useful tool for the prediction of in vivo data for estrogenic effects, without the need for additional animal toxicity tests.
摘要：
使用用于ER的hERα-HeLa-9903细胞和用于AR的MMTV/22Rv1_GR-KO细胞进行二苯甲酮化合物(BP)的雌激素受体(ER)和雄激素受体(AR)反式激活测定。结果表明，一些BP，如BP-1，BP-2，4OH-BP，4DHB,4-MBP,显示对ER的激动活性，RPCmax高于1nM17-β雌二醇。其他BP(BP，BP-3，BP-6，BP-7和BP-8）根据OECD测试指南（TG）455标准显示出较低的RPCmax，BP-4是唯一的ER阴性。然而,BPs的效力比参考化学品低至少1000倍，17-β-雌二醇。除了显示活性少量增加的BP-2外，没有一个BP对AR表现出激动活性。为了进一步评估基于综合测试和评估方法（IATA）方法的BP的雌激素效应，ER绑定上的现有数据，类固醇生成，MCF-7细胞增殖,收集和评估体内子宫营养测定。BPs的体外数据之间似乎有密切的联系，特别是ER转录活性，和体内子宫重量增加的结果。本案例研究表明，使用体外数据的综合方法可以成为预测体内雌激素效应数据的有用工具。无需额外的动物毒性试验。
