造成细胞毒性和DNA损伤的相同的化有机阻燃剂是否共享相同的途径?
Shengwu Yuan1, Hong Zhang1, Shuhang Wang1
1State Key Laboratory of Environmental Criteria and Risk Assessment, National Engineering Laboratory for Lake Pollution Control and Ecological Restoration, State Environment Protection Key Laboratory for Lake Pollution Control, Chinese Research Academy of Environmental Science, Beijing 100012, China.
Ecotoxicology and environmental safety
|February 28, 2024
概括
两个具有相似结构的化有机阻燃剂 (Cl-OPFR) 诱导了明显的细胞和分子损伤. 这项研究阐明了它们不同的毒性机制,这对于了解环境污染物的影响至关重要.
科学领域:
- 环境毒理学环境毒理学
- 分子毒理学分子毒理学
- 化学安全 化学安全 化学安全
背景情况:
- 有机阻燃剂 (OPFRs) 是新兴的污染物,其生物效应基本上未知.
- 化OPFRs (Cl-OPFRs) 的特定分子机制和共享关键事件 (KEs) 尚不清楚.
研究的目的:
- 调查两个Cl-OPFRs的细胞毒性,线粒体损伤,DNA损伤和分子机制:三二乙酸 (TCEP) 和三一二 (TCPP).
- 确定结构相似的Cl-OPFR是否具有共同的初始分子事件和KEEs.
主要方法:
- 实验室内生物测试用于评估细胞毒性,线粒体功能和DNA损伤.
- 技术包括测量细胞内活性氧物种 (ROS),线粒体超氧化物,流细胞计和实时PCR.
主要成果:
- 两种TCEP和TCPP都诱导了氧化应激介导的线粒体损伤和DNA损伤.
- 通过p53/Bax通路,TCPP触发了p53/p21介导的细胞周期停止和细胞亡,显示出更强的细胞毒性.
- 通过与TCPP相同的KE,TCEP没有诱导线粒体损伤和DNA损伤.
结论:
- 结构相似的Cl-OPFRs可以通过不同的分子机制产生毒性.
- 研究结果为开发不良结果途径和识别Cl-OPFRs的中间KEs提供了关键的见解.
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