通过代谢激活介导的异生菌化学物质的内分泌活性增加
Richard C Kolanczyk1, Jeffrey S Denny1, Barbara R Sheedy1
1Great Lakes Toxicology and Ecology Division, Office of Research and Development, Center for Computational Toxicology and Exposure, US Environmental Protection Agency, Duluth, Minnesota.
Environmental toxicology and chemistry
|September 15, 2023
概括
这项研究表明,像甲和4,4'-甲基氨基林这样的化学物质可以在鱼肝切片中代谢激活,从而增加雌激素受体活性和维特洛根因表达,这突显了在化学危害评估中考虑代谢的重要性.
科学领域:
- 环境毒理学和化学
- 在体外测定用于化学危害评估的测定.
- 内分泌干扰和雌激素受体相互作用
背景情况:
- 美国环境保护局 (USEPA) 要求对化学危害评估采用可靠的方法.
- 开发体外测试和定量结构-活性关系对于评估未经测试的化学品至关重要.
- 研究代谢激活途径是理解化学雌激素性的关键.
研究的目的:
- 研究导致鱼类雌激素性增加的化学物质的代谢激活.
- 评估化学物质及其代谢物的雌激素受体 (ER) 结合和雌激素介导基因表达.
- 了解由甲 (PLIN) 和4,4'-甲基乙氨酸 (MDA) 诱导维特洛素 (Vtg) 表达背后的机制.
主要方法:
- 使用彩虹鱼ER (rtER) 的竞争性结合试验.
- 在试验室中用试验化学品化鱼肝切片.
- 测量维氏素素 (Vtg) 表达和信使RNA (mRNA) 水平.
- 识别潜在的化学代谢产物.
主要成果:
- olphthalin (PLIN) 没有结合rtER,但其代谢物phenolphthalein (PLEIN) 是这样做的,并诱导了Vtg表达.
- 由PLIN诱导的Vtg表达被归因于其在鱼肝切片中的PLEIN代谢.
- 4,4'-甲基乙氨酸 (MDA) 不结合rtER,但诱导VtgmRNA,表明代谢激活.
- 研究了几种潜在的MDA代谢物,观察和测试了乙化MDA.
结论:
- 代谢激活在鱼类中的PLIN和MDA等化学物质的雌激素活性中起着重要作用.
- 使用鱼肝切片的体外测试对于研究代谢激活和内分泌干扰是有效的.
- 这些发现有助于开发化学危险评估的预测模型.
关键词:
4,4′-甲基二烯林是一种生物转化 生物转化雌激素受体的受体是什么代谢过程中的代谢.菲诺尔夫塔莱因 (Phenolphthalein) 是一种类物质.olphthalin 是一种类型的.彩虹鱼 彩虹鱼是一种更多相关视频
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