肺纤维细胞的单个和多分数α辐射之间的深度DNA基因组差异
Marilyn N Vera-Chang1, John M Danforth2, Marilyne Stuart3
1Radiobiology and Health Branch, Chalk River Laboratories, Canadian Nuclear Laboratories, Chalk River, ON, K0J 1J0, Canada.
Clinical epigenetics
|October 27, 2023
概括
阿尔法 (α) 辐射暴露会改变肺细胞中的DNA甲基化,单次暴露会降低甲基化,多次暴露会增加甲基化. 这些变化影响衰老和癌症基因,表明对辐射的适应性反应.
科学领域:
- 环境表观遗传学环境表观遗传学
- 辐射生物学 辐射生物学
- 基因组学就是基因组学.
背景情况:
- 阿尔法 (α) 辐射是一种具有表观毒性作用的环境剂.
- 人类暴露于α辐射可以通过吸入或核事故发生.
- DNA甲基化 (DNAm) 变化与衰老和癌症有关,但它们在α辐射肺细胞中的作用尚不清楚.
研究的目的:
- 研究单分量 (SF) 和多分量 (MF) α辐射对人类肺纤维细胞的DNA甲基组的影响.
- 为了确定与α辐射暴露相关的潜在DNAm生物标志物.
主要方法:
- 暴露于美国-241α来源的人类胚胎肺纤维细胞的全基因组DNAm分析.
- 使用了七种不同剂量的SF和MF暴露方案.
- 在基因体,瘤基因,瘤抑制基因和线粒体功能障碍相关基因中分析了差异甲基化区域.
主要成果:
- SF α辐射降低了DNAm水平,而MF辐射增加了DNAm.
- 基因体 (外子和内子) 是受SF和MF辐射影响最大的区域.
- 在与衰老,癌症和心血管疾病相关的基因中,MF辐射诱导了更差异化的甲基化区域.
- 多核射还影响了与线粒体功能障碍相关的基因,这表明了适应机制.
结论:
- 肺细胞甲基组对α辐射的反应取决于剂量和暴露方案 (SF与MF).
- 调查结果显示,SF和MF暴露的甲基组特征是截然不同的.
- 确定了用于疾病检测,预防和治疗的潜在α辐射生物标志物.
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