新兴的有机酸 Ester (resorcinol bis(diphenyl phosphate) 通过雌激素受体通路产生雌激素作用
1College of Life Sciences, China Jiliang University, 258 Xueyuan Street, Hangzhou, Zhejiang 310018, China; Institute of Environmental and Health Sciences, China Jiliang University, 168 Xueyuan Street, Hangzhou, Zhejiang 310018, China.
Toxicology
|October 12, 2023
概括
树脂二 (RDP) 通过激活雌激素受体,表现出比三 (TPHP) 更强烈的雌激素作用. 这一发现表明,由于其强烈的内分泌干扰活性,RDP可能会带来更大的健康风险.
科学领域:
- 环境科学 环境科学
- 毒理学 毒理学 毒理学
- 内分泌学 在内分泌学.
背景情况:
- 新兴的有机酸盐 (eOPEs) 越来越多地出现在环境中,人类暴露正在增加.
- 树脂二二酸盐 (RDP) 是室内灰尘中普遍存在的eOPE,但其毒性和健康风险尚不清楚.
研究的目的:
- 为了研究RDP的体外雌激素效应.
- 为了比较RDP的雌激素活性与遗留的有机酸盐三酸 (TPHP).
- 阐明RDP雌激素效应的潜在机制.
主要方法:
- MCF-7细胞增殖试验用于评估RDP和TPHP的影响.
- 雌激素受体 (ER) 抗剂,以确认ER的参与.
- 路西法酶记者基因测定ER转录活动.
- 竞争性光结合测试以确定ER结合亲和力.
- 分子对接模拟以可视化与ER结合口袋的相互作用.
主要成果:
- 在2.5μM时,RDP显著促进了MCF-7细胞的增殖,最大增强 (1.6倍) 比TPHP (1.3倍) 更大.
- RDP和TPHP激活了ER转录活性,而RDP显示了更高的活性.
- 与TPHP (5.6μM) 相比,RDP对ER的结合亲和力显著更高 (IC50 = 0.26μM).
- 分子对接揭示了ER结合口袋内RDP和TPHP的明显结合相互作用.
结论:
- RDP在体外表现出比TPHP更强烈的雌激素效应.
- RDP 的雌激素效应通过雌激素受体激活来调节.
- 与TPHP相比,RDP的强烈雌激素活性表明,与TPHP相比,对人类健康的风险可能更高.
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