Year: 2019
Type: dissertation
Abstract: Exposure to air pollution is associated with many serious diseases, such as asthma, chronic bronchitis, decreased lung function, cardiovascular disease, and lung cancer. Consequently, air pollution is currently contributing to significant increases in morbidity and mortality worldwide. Despite these adverse health effects, the cellular mechanisms underlying air pollutant-induced disease remain largely unknown. In this study we set out to investigate the genome-wide responses of lung cells exposed to multiple air pollutant exposure conditions. We first employ a toxicogenomic approach to evaluate the response of human lung cells exposed to gaseous pollutant mixtures present in urban atmospheres. Specifically, genomic responses are evaluated by identifying transcripts and molecular networks modulated upon exposure to freshly emitted air pollutants. These responses are then compared to those modulated upon exposure to photochemically altered pollutant mixtures, containing secondary pollutants. The results demonstrate that secondary pollutant mixtures produced from primary pollutants reacting under sunlight initiate a robust genomic response in lung cells, far greater than primary pollutants After identifying this trend, we focus a more detailed analysis on potential mechanisms underlying lung cell response to individual secondary pollutants. Here, we evaluate global microRNA expression modifications within lung cells exposed to formaldehyde, a secondary pollutant found in both indoor and outdoor air pollution. Our analysis reveals that formaldehyde induces significant changes in microRNA levels, which may in turn, regulate genes associated with inflammation and cancer. Together, these investigations reveal novel mechanisms potentially underlying air pollutant-induced disease.
DOI: 10.17615/21wc-ns91
Author: Rager, Julia Elizabeth
Institution: University of North Carolina at Chapel Hill
Language: English
Subfield: Health, Toxicology and Mutagenesis
Field: Environmental Science
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W2950480329