乙二氧化降低了dATP池,导致BEAS-2B细胞的复制压力和基因组不稳定性
Saddam Hussain1, Nayonika Mukherjee1, Natalie R Gassman1
1Department of Pathology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
The Journal of biological chemistry
|October 31, 2025
概括
迪氧 (DHA) 通过耗尽dATP,在肺细胞中引起DNA损伤和复制应激. 这种在无阳光制和蒸汽制品中观察到的基因毒性作用是部分可逆的,并且与氧化应激有关.
科学领域:
- 细胞生物学 细胞生物学
- 基因毒理学 基因毒理学
- 分子毒理学分子毒理学
背景情况:
- 二氧化 (DHA) 存在于无阳光制品和电子烟气溶中.
- 以前的研究表明,DHA诱导细胞毒性,基因毒性,细胞循环停止和线粒体应激.
- DHA对DNA复制压力和基因组不稳定性的影响仍然在很大程度上是未知的.
研究的目的:
- 研究DHA暴露对肺上皮细胞 (BEAS-2B) 的影响.
- 为了确定DHA是否诱导复制压力和基因组不稳定性.
- 阐明DHA的基因毒性的潜在分子机制.
主要方法:
- 对BEAS-2B细胞暴露于DHA.
- 评估氧化应激标志物 (53BP1焦点).
- 对DNA损伤反应途径的评估 (pChk2,pP53).
- 用DNA纤维测试来测量复制叉的进展.
- 核酸生物合成和dATP池的分析.
- 评估微核的形成.
- 腺因补充剂对DHA诱导的损伤的影响.
主要成果:
- 急性DHA暴露诱导了氧化应激和DNA双链断裂反应.
- DHA暴露减少了复制叉的进展和增加了微核的形成.
- DHA降低了核酸减少酶的表达和减少了dATP池.
- 氨酸补充部分挽救了复制应激,DNA病变和细胞毒性.
- 在去除DHA后,复制应激和DNA损伤是部分可逆的.
结论:
- DHA在肺上皮细胞中诱导DNA损伤和复制应激,主要是通过dATP池耗尽.
- 氨酸补充剂减轻了一些,但不是所有的,DHA诱导的基因毒性作用.
- 其他机制可能有助于DHA对线粒分裂的影响,这需要进一步研究.
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