Fine particulate matter smaller than 2.5 micrometers in diameter (PM2.5), found in diesel exhaust or smoke from indoor cooking, has consistently been established as a potent promoter of lung cancer. Preliminary cell culture data suggest that PM2.5 may also cause DNA damage directly and play a role in lung cancer pathogenesis. Specifically, it can promote tumorigenesis through an influx of macrophages and release of interleukin-1β.1
“PM2.5 is particularly dangerous because it is able to accumulate in the most distal airways,” said Peiyao Wang, an MD and PhD student in the Lockwood Lab at the University of British Columbia, Vancouver. “It has been well established that PM2.5 can drive lung tumor promotion and eventually cancer development. We found that at the highest concentrations, cell colony formation was comparable to our positive control exposure—tobacco smoke condensate.”
Wang discussed the role of PM2.5 in the development of lung cancer during the 2025 World Congress on Lung Cancer in Barcelona, Spain.2 She reviewed previous studies showing that PM2.5 can promote tumor formation following a genotoxic event. Additionally, she said early results from in vitro studies of malignant transformation and DNA damage found that as few as three 24-hour exposures to PM2.5 induced a physical alteration in the BEAS-2B cell line, changing their normal polygonal shape to an elongated, mesenchymal-like morphology with spindle-like protrusions. The morphologic transformation was not reversible.
Longer exposure (six 24-hour cycles) induced significant anchorage-independent growth of cell colonies in soft agar that was dose dependent. Colony formation at the highest PM2.5 concentrations tested were comparable to levels seen in the control arm exposed to tobacco smoke concentrate. PM2.5 increased mutational burden, also in a dose-dependent manner.
The clinical implications of these early findings are unclear, Wang said. Tissue cultures exposed to PM2.5 are being analyzed using whole genome sequencing for comparison with human lung adenocarcinoma samples from patients without a smoking history. Those same patients are being stratified by their past PM2.5 exposure levels, calculated via their detailed residential history.
“We want to see if once we stratify patients into high vs low PM2.5 exposure groups, we find mutational signatures or aberrant DNA alterations similar to those we are seeing in a controlled cell culture setting,” she explained. “There have been lung cancer patients who have been massively sequenced and who have never smoked, but they have never had that PM2.5 exposure piece well detailed.”
Tobacco smoke is both a tumor initiator and tumor promoter, Wang said. PM2.5 is well established as a promoter in cells with preexisting epidermal growth factor receptor mutations. If PM2.5 is also associated with tumor initiation, then that would help make the case for including air pollution exposure in lung cancer screenings as an additional risk factor.
“There’s a lot of data showing that urban centers have high, dense levels of ambient air pollution,” Wang said. “These early results suggest PM2.5 is causing permanent DNA damage, which could have implications for lung cancer screening. There are also treatment implications if we can find therapeutic targets specific to air pollution, but these are very early days for that kind of research… We are actively trying to figure out how pollution fits into that goal.”
References
1. Murphy C, Pandya T, Swanton C, Solomon BJ. Lung cancer in nonsmoking individuals: a review. JAMA. Published online October 20, 2025. doi:10.1001/jama.2025.17695
2. Wang P, Naso J, Myers R, et al. MA09.03 Determining the Role of Fine Particulate Matter (PM2.5) in Lung Cancer Initiation. J Thorac Oncol. 2025;20(10):S91-S92. doi:10.1016/j.jtho.2025.09.166
