DNA hydroxymethylation landscape and mitochondrial DNA in lung fibroblasts exhibit specific signatures of single- and multi-fraction alpha-particle radiation

Alpha-radiation, the most significant natural source of ionizing radiation to which humans are exposed, is a genotoxic and epigenotoxic agent capable of increasing cancer risks. Human exposure to alpha-radiation to unsafe levels can occur as a result of a single exposure from a nuclear incident or repetitive exposures via inhalation of naturally occurring radon gas that accumulates in enclosed spaces. DNA hydroxymethylation (DNAhm) is an intermediary step in the DNA demethylation pathway and an understudied epigenetic event that can regulate gene expression. Due to the DNAhm enrichment in the brain, the few studies available focus on the role of DNAhm in this tissue. The effects of single or multiple alpha-radiation events on the DNAhm of human lung cells remain unexplored. Here, we used our 64 alpha-irradiated human embryonic lung fibroblast samples from our 2023 methylome study to examine their genomic-wide DNAhm profile.

α辐射（Alpha-radiation）是人类暴露的最主要天然电离辐射源，属于可增加癌症风险的遗传毒性与表观遗传毒性因子。人类暴露于不安全剂量水平的α辐射，可能源于核事故单次辐照，或是因吸入封闭空间中积聚的天然氡气而反复受到辐照。DNA羟甲基化（DNA hydroxymethylation，DNAhm）是DNA去甲基化通路中的中间步骤，也是一种尚未得到充分研究的表观遗传事件，可调控基因表达。鉴于DNAhm在大脑组织中富集，现有少数研究均聚焦于其在该组织中的作用。单次或多次α辐照事件对人类肺细胞DNAhm的影响仍未被探明。本研究利用2023年甲基化组研究中获取的64份α辐照人胚肺成纤维细胞样本，对其全基因组DNAhm谱进行了分析。