Thirdhand cigarette smoke (THS) is a newly described toxin that lingers in the indoor environment long after cigarettes have been extinguished. Emerging results from both cellular and animal model studies suggest that THS is a potential human health hazard. DNA damage derived from THS exposure could have genotoxic consequences that would lead to the development of diseases. However, THS exposure‐induced interference with fundamental DNA transactions such as replication and transcription, and the role of DNA repair in ameliorating such effects, remain unexplored. Here, we found that THS exposure increased the percentage of cells in S‐phase, suggesting impaired S‐phase progression. Key DNA damage response proteins including RPA, ATR, ATM, CHK1, and BRCA1 were activated in lung cells exposed to THS, consistent with replication stress. In addition, THS exposure caused increased 53BP1 foci, indicating DNA double‐strand break induction. Consistent with these results, we observed increased micronuclei formation, a marker of genomic instability, in THS‐exposed cells. Exposure to THS also caused a significant increase in phosphorylated RNA Polymerase II engaged in transcription elongation, suggesting an increase in transcription‐blocking lesions. In agreement with this conclusion, ongoing RNA synthesis was very significantly reduced by THS exposure. Loss of nucleotide excision repair exacerbated the reduction in RNA synthesis, suggesting that bulky DNA adducts formed by THS are blocks to transcription. The adverse impact on both replication and transcription supports genotoxic stress as a result of THS exposure, with important implications for both cancer and other diseases.

中文翻译：

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接触二手烟会导致复制压力并损害人肺细胞的转录。

二手香烟烟雾（THS）是一种新近描述的毒素，在香烟熄灭后很长一段时间仍会在室内环境中徘徊。细胞和动物模型研究的最新结果表明，THS是对人类健康的潜在危害。THS暴露引起的DNA损伤可能具有遗传毒性后果，从而导致疾病的发展。但是，尚未探索THS暴露诱导的对基本DNA交易（例如复制和转录）的干扰以及DNA修复在改善此类影响方面的作用。在这里，我们发现THS暴露增加了S期细胞的百分比，表明S期进程受损。与复制压力一致，在暴露于THS的肺细胞中激活了关键的DNA损伤应答蛋白，包括RPA，ATR，ATM，CHK1和BRCA1。此外，THS暴露引起53BP1病灶增加，表明DNA双链断裂诱导。与这些结果一致，我们在暴露于THS的细胞中观察到微核形成增加，这是基因组不稳定的标志。暴露于THS还会引起参与转录延伸的磷酸化RNA聚合酶II的显着增加，表明转录阻滞性病变的增加。与该结论一致，THS暴露可显着减少正在进行的RNA合成。核苷酸切除修复的丢失加剧了RNA合成的减少，这表明THS形成的庞大DNA加合物是转录的障碍。THS暴露对复制和转录的不利影响都支持遗传毒性应激，这对癌症和其他疾病均具有重要意义。