探索双醇在雌激素受体上具有非单调剂量反应曲线的对抗作用
Jiahui Su1,2, Xiaoxi Yang1, Dingyi Wang1
1State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
非单调的剂量反应曲线 (NMDRCs) 是内分泌干扰化学物质 (EDCs) 的特征. 这项研究揭示了一些双因细胞毒性而表现出非特异性抑制雌激素受体 (ER) 活性,而不是特异性对抗性.
科学领域:
- 环境毒理学环境毒理学
- 分子内分泌学分子内分泌学
- 化学安全 化学安全
背景情况:
- 非单调剂量反应曲线 (NMDRCs) 是常见的内分泌干扰化学物质 (EDCs) 与核受体 (NRs) 相互作用.
- 了解这些复杂的相互作用对于评估化学安全和环境影响至关重要.
研究的目的:
- 选11 bisphenols在雌激素受体 (ER) 上的激进和对抗性活动.
- 研究观察到的NMDRC背后的机制,特别是区分特定的对抗性和一般细胞毒性.
主要方法:
- 利用MVLN细胞选11种双,以检测ER的激进和对抗活性.
- 观察到的剂量反应模式包括S形,倒置S形和钟形的形状.
- 在高度下研究了特定双 (BPB,BPAF) 对于ER抗作用,评估细胞活力并与已知的ERα抗剂 (4OHT) 进行比较.
主要成果:
- 确定了三种不同的剂量反应模式:agonistic (S形),antagonistic (反转的S形) 和nonmonotonic (钟形).
- 观察到高度的双乙烯 (BPB) 和双乙烯 (BPAF) 导致细胞活力下降,表明细胞基线毒性.
- 证明了BPB和BPAF对ER交换激活的抑制作用是不特定的,可能是由于与水性相关的毒性,与4OHT的特定作用不同.
结论:
- 对NR转活的抑制作用并不总是意味着特定的对抗活性;细胞毒性可能是一个混因素.
- 建议在以NR对抗为中心的EDC效应查时,仔细评估信号减弱特异性.
- 强调在新兴化学品风险评估中需要谨慎解释NMDRC.
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