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取代BPA:结构替代品BPAF与孕激素受体结合提高了乳腺癌风险
Xiaotong Ji1, Peilin Li1, Haoyang Wu1
1Department of Environmental Health, School of Public Health, Shanxi Key Laboratory of Environmental Health Impairment and Prevention, MOE Key Laboratory of Coal Environmental Pathogenicity and Prevention, Shanxi Medical University, Taiyuan, Shanxi, 030001, P. R. China.
取代BPA的双相似物 (BPs) 构成环境健康风险. 研究表明BP,像BPAF一样,与孕激素受体 (PR) 结合,促进乳腺癌,表明风险仅仅是转移而不是减轻.
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:
- 全球双相似物 (BPs) 的生产正在增加,作为受监管双A (BPA) 的替代品.
- 对BP的环境存在和乳腺癌风险尚不清楚,这引起了公众健康的担忧.
研究的目的:
- 通过检查它们与孕激素受体 (PR) 的结构亲和力来研究双类型 (BPs) 的环境风险.
- 通过不同的实验水平,将PR结合与瘤性结果联系起来.
主要方法:
- 分子模拟以评估BP与PR-连接体结合域 (LBD) 的结合亲和力.
- 化学测定和细胞热转移测定以确认PR-LBD结构变化和相互作用.
- 关于PR表达和细胞迁移/侵入的体外研究.
- 使用小鼠模型进行乳腺瘤生长的体内研究.
- 毒理学优先级指数用于风险分层.
主要成果:
- 与BPA相比,BPAF和BPB对PR-LBD的结合比BPA更强.
- 暴露于BP引起了持续的PR-LBD结构变化,表明内分泌干扰.
- 在人体相关度下,BPAF和BPF增加了PR表达.
- 暴露于BPAF加速了小鼠的乳腺瘤生长,与PR上调相关.
- 根据结合亲和力和细胞毒性,BPAF被确定为具有最高风险的模拟物.
结论:
- 用类似的类似物代替BPA并不能消除环境健康风险,而是将它们转移.
- 双相似物由于它们与孕激素受体的相互作用而带来重大风险,孕激素受体是乳腺癌发展的关键因素.
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