对133种生理相关的环境化学物质进行生殖毒性选和表征
Gurugowtham Ulaganathan1, Hui Jiang1, Noah Canio1
1Institute for Society and Genetics, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
Reproductive toxicology (Elmsford, N.Y.)
|May 9, 2024
概括
在C. elegans中进行高通量测试,确定了13种生殖毒素,包括四级化合物 (QAC). 这种可扩展的体内方法有助于评估生殖环境化学风险.
科学领域:
- 生殖毒理学 生殖毒理学
- 环境健康 环境健康
- 模型生物研究研究
背景情况:
- 生殖涉及复杂的相互作用,需要强大的毒性评估方法.
- 环境化学物质对生殖健康构成风险.
- 需要可扩展的测试模型来进行全面的化学安全评估.
研究的目的:
- 在C. elegans中适应和实施高通量染色体分离试验,用于生殖毒性查.
- 使用C. elegans. 选133种生理上相关的化学物质,以检测它们的生殖毒性.
- 为了比较C. elegans体内结果与现有的体外数据 (ToxCast,ICE).
主要方法:
- 调整了低通量C. elegans染色体分离试验以用于高通量查.
- 利用公共数据源 (ToxCast,ICE) 进行化学品的选择和表征.
- 通过独立的体内胚胎活力试验验证实查结果.
- 将C. elegans的数据与700多个细胞反应和300多个途径的ToxCast体外测定进行了比较.
主要成果:
- 将13种化学物质归类为生殖毒素.
- 已确定四级化合物 (QAC) 作为高度活性的生殖毒素.
- 在顶部和底部的化学物质之间,在生物活性或强度 (AC50) 中没有观察到显著的差异.
- 在目标类别中发现了显著的差异,对于高Z分数化学物质,类固醇激素标的过度代表性.
结论:
- 高通量体内C. elegans模型对于可扩展的生殖毒性评估是有价值的.
- 四级化合物 (QAC) 需要对其对生殖健康的影响进行优先评估.
- 在体外模型为体外测定提供了补充数据,以全面了解化学毒性.
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