在彩虹鱼In Vitro模型中,,基和分支的ER结合和维特洛根因激进作用
Mark A Tapper1, Jeffrey S Denny1, Jose A Serrano1
1US Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory, Mid-Continent Ecology Division, 6201 Congdon Boulevard, Duluth, MN 55804, United States.
和基可以与彩虹鱼雌激素受体 (rtER) 结合,并诱导维特洛根因 (Vtg) 基因表达. 一些化学物质在肝脏内转化为活性化合物,突出显示了潜在的内分泌干扰风险.
科学领域:
- 环境毒理学环境毒理学
- 内分泌学 在内分泌学.
- 生物化学 生物化学
背景情况:
- 和基是常见的工业化学品,具有潜在的内分泌干扰性质.
- 评估这些化合物的雌激素活性对于环境保护至关重要.
- 雌激素受体 (ER) 介导的途径是理解化学毒性的关键目标.
研究的目的:
- 用彩虹鱼模型研究和氧的雌激素潜力.
- 评估与雌激素受体的化学结合和下游基因诱导.
- 应用一个不良结果路径 (AOP) 框架来评估内分泌干扰.
主要方法:
- 在实验室中使用彩虹鱼雌激素受体 (rtER) 结合试验.
- 使用的肝脏切片维特洛根因 (Vtg) mRNA诱导试验.
- 在定义的ER介导的AOP框架内进行综合测试.
主要成果:
- 循环子,分支子和氧子子对rtER表现出不同的结合亲和力.
- 许多测试的化合物在彩虹鱼肝脏片中成功诱导了Vtg基因表达.
- 环基,最初是无约束性的,在肝脏组织中生物转化为活性Vtg诱导剂.
结论:
- 和基芬具有雌激素活性,对水生生物构成潜在风险.
- 这项研究表明,在AOP中对测定化学内分泌干扰的序列性体外试验的实用性.
- 目标组织内的生物转化可能导致其他无活性化合物的激活,需要进行全面的毒性评估.
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