Theses
Date of Award
2025
Document Type
Thesis
Degree Name
Master of Science (MS)
Department
Biological Sciences
First Advisor
Dr. Hayley McDaid
Second Advisor
Dr. Kristina Ames
Abstract
Air pollution is a global issue that has been correlated to the increased incidence of several diseases, including lung cancer. Particulate matter 2.5 (PM2.5) is a category of air pollutants describing microscopic aggregates with a diameter of 2.5 microns or less. These particles are composed of diverse chemicals, and are generally enriched for heavy metals and polycyclic aromatic hydrocarbons (PAHs), some of which are classified as potential carcinogens by the International Agency for Research on Cancer (IARC) and the Environmental Protection Agency (EPA). Sources of PM2.5 vary from natural to industrial, and in general, urban areas tend to have elevated levels of PM2.5 due to high industrial and commercial activities. Studies on the effects of PM2.5 have shown that exposure to these particles can induce mutations and double stranded DNA breaks. Furthermore, exposure to PM2.5 has also been shown to promote accelerated tumor growth and to increase metastatic traits in cancer cells. However, the mechanisms through which PM2.5 exposure impacts lung cancer etiology remain unclear. Currently, it is not known whether the cellular and genomic damage induced by PM2.5 exposure are due to the particles themselves or the different chemicals that constitute these particles. Additionally, the impact of PM2.5 exposure on cancer recurrence and disease-free survival is not well understood. In this project, we use primary, genomically unaltered, bronchial-tracheal epithelial cells to evaluate how PM2.5 exposure contributes to lung cancer etiology. We also K-ras mutant lung cancer cells to assess how PM2.5 exposure impacts lung cancer progression and relapse through the lens of dormancy, specifically senescence. We hypothesize that PM2.5 accumulates intracellularly, altering both the cell fate and the genomic landscape of lung cells. These effects may be mediated by either the chemicals found in PM2.5, the particles themselves, or both. To test this hypothesis, we investigated: 1) the dose-dependent effects of PM2.5 and selected chemical constituents on cell fate, namely apoptosis, proliferation, and senescence; 2) the dynamics of PM2.5 uptake, and 3) the effects of chronic PM2.5 and its chemical constituents on the genomic landscape of primary lung epithelial cells. For cancer cells, we evaluated the dynamics of PM2.5 uptake in proliferating and senescent cancer cells, as well as the effects of PM2.5 exposure on senescence escape. Our results show that PM2.5 exposure suppresses proliferation and induces EGFR copy number changes under acute and chronic exposure conditions, respectively. These effects may be mediated by particle accumulation intracellularly and interactions between the chemicals found in PM2.5. Furthermore, we show that senescent cells are more susceptible to PM2.5 accumulation, and this increased particle accumulation may promote senescence escape. These findings provide insight as to how environmental pollution, specifically PM2.5 and the chemicals associated with it, may influence lung cancer development and progression.
Recommended Citation
Bualuti, Gracia Mbangu, "Unmasking the Silent Threat of PM2.5: A Toxic Mix of Particles and Chemicals" (2025). CUNY Academic Works.
https://academicworks.cuny.edu/le_etds/41
