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J. Hazard. Mater., 2023 Aug 6;459:132238 | https://doi.org/10.1016/j.jhazmat.2023.132238 Urban dust particles disrupt mitotic progression by dysregulating Aurora kinase B-related functions

Jaewook Ryu ^a,b, Seung Hyeun Lee^c, Sungyeon Kim ^d, Joo-Won Jeong ^a,e, Kyung Sook Kim ^f, Seungyoon Nam ^d,g, Ja-Eun Kim ^a,b,h

^aDepartment of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, the Republic of Korea
^bDepartment of Pharmacology, College of Medicine, Kyung Hee University, Seoul 02447, the Republic of Korea
^cDivision of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Kyung Hee University, Seoul 02447, the Republic of Korea
^dDepartment of Genome Medicine and Science, AI Convergence Center for Medical Science, Gachon Institute of Genome Medicine and Science, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon 21565, the Republic of Korea
^eDepartment of Anatomy and Neurobiology, College of Medicine, Kyung Hee University, Seoul 02447, the Republic of Korea
^fDepartment of Biomedical Engineering, College of Medicine, Kyung Hee University, Seoul 02447, the Republic of Korea
^gDepartment of Health Sciences and Technology, Gachon Advanced Institute for Health Sciences and Technology (GAIHST), Gachon University, Incheon 21999, the Republic of Korea
^hDepartment of Precision Medicine, Graduate School, Kyung Hee University, Seoul 02447, the Republic of Korea

Correspondence to: Ja-Eun Kim

Abstract

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.

논문정보

형식Research article
게재일2023년 08월 (BRIC 등록일 2023-08-22)
연구진국내 연구진
분야 의약학 > 약리의학

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