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

## TL;DR

Northern Thailand's biomass haze PM2.5 causes oxidative stress and gene changes in lung cancer cells, depending on their genetic makeup.

## Contribution

This study reveals genotype-specific effects of biomass-derived PM2.5 on lung cancer cell viability and transcriptomes.

## Key findings

- PM2.5 exposure caused viability loss in A549 and NCI-H1975 cells more than in NCI-H460.
- Genotype-specific oxidative stress patterns were observed, with A549 showing cumulative ROS increases.
- RNA-seq identified activation of xenobiotic metabolism and repression of tumor suppressors.

## Abstract

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 (KRAS-mutant), NCI-H1975 (EGFR-mutant), and NCI-H460 (KRAS/PIK3CA-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 (CYP1A1, CYP1B1), oxidative/metabolic stress mediators (GDF15, TIPARP), and tumour-associated genes (FOSB, VGF), alongside repression of tumour suppressors (FAT1, LINC00472). 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.