Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, the Republic of Korea; Department of Pharmacology, College of Medicine, Kyung Hee University, Seoul 02447, the Republic of Korea.
Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Kyung Hee University, Seoul 02447, the Republic of Korea.
J Hazard Mater. 2023 Oct 5;459:132238. doi: 10.1016/j.jhazmat.2023.132238. Epub 2023 Aug 6.
Particulate matter (PM), a major component of outdoor air pollution, damages DNA and increases the risk of cancer. Although the harmful effects of PM at the genomic level are known, the detailed mechanism by which PM affects chromosomal stability remains unclear. In this study, we investigated the novel effects of PM on mitotic progression and identified the underlying mechanisms. Gene set enrichment analysis of lung cancer patients residing in countries with high PM concentrations revealed the downregulation of genes associated with mitosis and mitotic structures. We also showed that exposure of lung cancer cells in vitro to urban dust particles (UDPs) inhibits cell proliferation through a prolonged M phase. The mitotic spindles in UDP-treated cells were hyperstabilized, and the number of centrioles increased. The rate of ingression of the cleavage furrow and actin clearance from the polar cortex was reduced significantly. The defects in mitotic progression were attributed to inactivation of Aurora B at kinetochore during early mitosis, and spindle midzone and midbody during late mitosis. While previous studies demonstrated possible links between PM and mitosis, they did not specifically identify the dysregulation of spatiotemporal dynamics of mitotic proteins and structures (e.g., microtubules, centrosomes, cleavage furrow, and equatorial and polar cortex), which results in the accumulation of chromosomal instability, ultimately contributing to carcinogenicity. The data highlight the novel scientific problem of PM-induced mitotic disruption. Additionally, we introduce a practical visual method for assessing the genotoxic outcomes of airborne pollutants, which has implications for future environmental and public health research.
颗粒物（PM）是室外空气污染的主要成分，它会破坏 DNA 并增加癌症风险。尽管已知 PM 在基因组水平上的有害影响，但 PM 影响染色体稳定性的详细机制仍不清楚。在这项研究中，我们研究了 PM 对有丝分裂进程的新影响，并确定了潜在的机制。对居住在 PM 浓度高的国家的肺癌患者进行基因集富集分析，揭示了与有丝分裂和有丝分裂结构相关的基因下调。我们还表明，体外暴露于城市粉尘颗粒（UDPs）会通过延长 M 期抑制肺癌细胞的增殖。UDP 处理的细胞中的有丝分裂纺锤体过度稳定，中心体数量增加。从极性皮质切入的分裂沟和肌动蛋白清除的速度显著降低。有丝分裂进程的缺陷归因于早期有丝分裂时着丝粒处 Aurora B 的失活，以及晚期有丝分裂时纺锤体中间区和中间体。虽然之前的研究表明 PM 与有丝分裂之间可能存在联系，但它们并没有特别确定有丝分裂蛋白和结构（例如微管、中心体、分裂沟、赤道和极皮质）的时空动态失调，这导致染色体不稳定性的积累，最终导致致癌性。这些数据突出了 PM 诱导的有丝分裂破坏这一新颖的科学问题。此外，我们引入了一种实用的视觉方法来评估空气传播污染物的遗传毒性结果，这对未来的环境和公共卫生研究具有重要意义。
