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The heterogeneity and complexity of solvent-extracted organic matter associated with PM 2.5 (SEOM-PM 2.5 ) is well known; however, there is scarce information on its biological effects in human cells. This work aimed to evaluate the effect of SEOM-PM 2.5 collected in northern Mexico City during the cold-dry season (November 2017) on NL-20 cells, a human bronchial epithelial cell line. The SEOM obtained accounted for 15.5% of the PM 2.5 mass and contained 21 polycyclic aromatic hydrocarbons (PAHs). The cell viability decreased following exposure to SEOM-PM 2.5 , and there were noticeable morphological changes such as increased cell size and the presence of cytoplasmic vesicles in cells treated with 5-40 μg/mL SEOM-PM 2.5 . Exposure to 5 μg/mL SEOM-PM 2.5 led to several alterations compared with the control cells, including the induction of double-stranded DNA breaks based (p < 0.001); nuclear fragmentation and an increased mitotic index (p < 0.05); 53BP1 staining, a marker of DNA repair by non-homologous end-joining (p < 0.001); increased BiP protein expression; and reduced ATF6, IRE1α, and PERK gene expression. Conversely, when exposed to 40 μg/mL SEOM-PM 2.5 , the cells showed an increase in reactive oxygen species formation (p < 0.001), BiP protein expression (p < 0.05), and PERK gene expression (p < 0.05), indicating endoplasmic reticulum stress. Our data suggest concentration-dependent toxicological effects of SEOM-PM 2.5 on NL-20 cells, including genotoxicity, genomic instability, and endoplasmic reticulum stress., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)