Urban dust particles disrupt mitotic progression by dysregulating Aurora kinase B-related functions.

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.

• Authors: Jaewook Ryu, Seung Hyeun Lee, Sungyeon Kim, Joo-Won Jeong, Kyung Sook Kim, Seungyoon Nam, Ja-Eun Kim
• Journal: Journal of hazardous materials (J Hazard Mater) Vol. 459 Pg. 132238 (10 05 2023) ISSN: 1873-3336 [Electronic] Netherlands
• PMID: 37586242 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.

Chemical References

• Aurora Kinase B
• Dust
• Particulate Matter

Topics

• Humans
• Aurora Kinase B (genetics, metabolism)
• Dust
• Mitosis
• Spindle Apparatus (metabolism)
• Particulate Matter (toxicity, metabolism)
• Lung Neoplasms (metabolism)