Biomass-Haze PM2.5 from Northern Thailand Drives Genotype-Specific Oxidative Stress and Transcriptomic Remodeling in Non-Small-Cell Lung Cancer Cells

Fine particulate matter (PM2.5) is a major air pollutant linked to lung cancer progression. In Southeast Asia, seasonal smoke-haze produces biomass-derived PM2.5, yet its acute effects on genetically diverse lung tumours remain unclear. We investigate how Chiang Mai haze-derived PM2.5 impacts oxidative stress and gene expression in three non-small-cell lung cancer (NSCLC) cell lines: A549 (<i>KRAS</i>-mutant), NCI-H1975 (<i>EGFR</i>-mutant), and NCI-H460 (<i>KRAS/PIK3CA</i>-mutant). Cells were exposed to PM2.5 (0-200 µg/mL) and assessed for viability (MTT), reactive oxygen species (ROS; H₂O₂, •OH) and malondialdehyde (MDA) levels, mitochondrial-associated fluorescence, and whole-transcriptome responses. Acute exposure caused dose- and time-dependent viability loss, with A549 and NCI-H1975 more sensitive than NCI-H460. ROS profiling normalized to viable cells revealed genotype-specific oxidative patterns: cumulative increases in A549, sharp reversible spikes in NCI-H1975, and modest changes in NCI-H460. MitoTracker intensity trended downward without significance, with subtle fluorescence changes and particulate uptake. RNA-seq identified robust induction of xenobiotic metabolism (<i>CYP1A1</i>, <i>CYP1B1</i>), oxidative/metabolic stress mediators (<i>GDF15</i>, <i>TIPARP</i>), and tumour-associated genes (<i>FOSB</i>, <i>VGF</i>), alongside repression of tumour suppressors (<i>FAT1</i>, <i>LINC00472</i>). Pathway enrichment analyses highlighted oxidative stress, IL-17, NF-κB, and immune checkpoint signaling. Together, biomass haze-derived PM2.5 from Northern Thailand drives genotype-dependent oxidative stress and transcriptional remodeling in NSCLC cells.