Characterization of the Chemical Composition, Cytotoxicity, and Metabolomic Effects of PM2.5 in a Plateau City, China

The health impacts of atmospheric fine particulate matter (PM_2.5) in plateau regions have attracted concerns, along with local population growth and rapid urbanization. This study collected PM_2.5 samples at summer and winter in Xining, a city located in the northeastern Tibetan Plateau. The chemical composition of PM_2.5 and its cytotoxicity on human lung epithelial cells (A549) are characterized, and composition-cytotoxicity correlation is discussed. The toxic mechanisms of PM_2.5 in different seasons were further investigated through metabolomic analysis using high-resolution mass spectrometry. The average PM_2.5 mass concentration in Xining during winter was 2.10 times higher than that during summer. The carbonaceous components in PM_2.5 were dominated by OC, while the main water-soluble ions were SO₄^2-, NO₃^-, and NH₄⁺, with Mg, Al, Fe, and Ca also present in high concentrations in metal elements. LDH and ROS emerged as the most PM_2.5-affected toxicity indices in summer (34.59 ± 4.86 ng/L, 1.19× control) and winter (8.62 ± 1.25 ng/mL, 1.77× control), respectively. OC, Cl^-, F^-, Sn, Cr, SO₄^2-, Pb, Zn, Mg, NO₃^-, and NH₄⁺ may synergistically exacerbate oxidative stress and inflammatory responses on A549 cells in Xining. Furthermore, glutathione metabolism, amino acid metabolism, and sphingolipid metabolism were identified as key pathways influencing cellular oxidation and inflammation. Thimonacic, 9-(2,3-dihydroxypropoxy)-9-oxononanoic acid, and hypoxanthine were common metabolites in both seasons. Our findings greatly enhance the understanding of health risks associated with PM_2.5 in the plateau city.