Title: Cache Valley air pollution damages DNA and increases cancer risk

Name: Rachel Sagers
Mentor: Dr. Roger Coulombe

The scenic mountain views of Cache Valley in Northern Utah stand in stark contrast with the valley’s high concentrations of fine particulate air pollution (PM2.5), some of the worst reported in the United States. The unique geography promotes formation of ammonium nitrate (NH4NO3) from nitrogen oxides produced by motor vehicles and ammonia from dairy cow excreta. Winter atmospheric inversions, exacerbated by the mountainous terrain, trap and concentrate air pollutants. Epidemiological studies have revealed an association between PM exposure and early all-cause mortality. Exposure to PM2.5 is also associated with a variety of cardiovascular, cardiopulmonary, and neurodegenerative diseases, including myocardial infarction, stroke, COPD, lung cancer, Alzheimer’s disease, and Parkinson’s disease. Previous studies have shown that Cache Valley PM (CVPM) has pro-inflammatory effects, which has been linked to enhanced activation of Akt in human pulmonary epithelial cells. This research examined the cellular responses of human lung (BEAS-2B) cells exposed to CVPM and diesel exhaust particles (DEP), at 1 and 12 µg/ml concentrations of each particle type for a 24 hour exposure period. The CVPM used was collected onto stainless steel plates by a Tisch impactor. Assessment by the comet assay reveal genetic damage to CVPM exposed cells with equal potency to DEP exposed cells. Flow cytometry (p < 0.05) showed CVPM exposed cells had a significant increase in the number of actively-dividing cells compared to control cells. Whole-genome microarray identified affected genes related to inflammatory pathways, as well as activated Akt-dependent pathways. Subsequent qRT-PCR showed that CVPM exposure significantly increased expression of inflammatory markers, including IL-6, CD40LG, PLAG27, and cytochrome P450 (CYP) 1A1 (p < 0.05). Immunoblotting confirmed activation of Akt by phosphorylation of Thr308 in both CVPM and DEP exposed cells. This data supports the hypothesis that CVPM may induce pro-carcinogenic pathways with potency similar to DEP.