Abstract 317: Particulate matter accumulates chromosomal instability during mitosis

Abstract

Abstract Particulate matter (PM), a major component of outdoor air pollution triggers genotoxicity as well as cytotoxicity. Although the harmful effects of PM on DNA damage and its carcinogenic risk have been thoroughly studied, the detailed mechanism by which PM affects chromosomal stability remains unclear. Maintenance of chromosome is finely monitored during mitotic phase through multiple proteins and structures. The present study shows that treatment of urban particulate matter (UPM) inhibited proliferation of lung cells through the accumulation of chromosomal instability which is determined by the formation of multinucleation and macronucleation. In particular, PM treatment prolonged mitotic duration. This delay in mitotic progression resulted from inactivation of Aurora B at prometaphase and metaphase, causing a failure in dynamic stabilization of kinetochore-microtubule attachment. In addition, ingression rate of cleavage furrow and actin clearing from polar cortex were significantly reduced at telophase. It indicates that dysregulation of spatiotemporal dynamics of mitotic proteins and structures finally disturbs cytokinetic division. Overall, PM leads to accumulation of chromosomal instability, finally contributing to its carcinogenicity. Citation Format: Jaewook Ryu, Ja-Eun Kim. Particulate matter accumulates chromosomal instability during mitosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 317.