Understanding the Biological Effects of Isoprene-Derived Secondary Organic Aerosol

Isoprene (2-methyl-1,3-butadiene), a volatile organic compound released primarily by terrestrial vegetation, is an important precursor to the formation of secondary organic aerosol (SOA). Isoprene-derived SOA, which comprises a large mass fraction of global fine particulate matter (PM2.5), results from the atmospheric chemical transformations of isoprene with controllable anthropogenic emissions such as oxides of nitrogen (NOx) and sulfur dioxide. Because PM2.5 from isoprene is a relatively new discovery, little is known about its toxicity. Through a series of in vitro exposure studies, we explored the effects of isoprene-derived SOA on oxidative stress-related gene expression levels in human bronchial epithelial cells (BEAS-2B). We generated atmospherically-relevant compositions of isoprene-derived SOA in an outdoor smog chamber, starting from isoprene as a precursor in the presence of NOx and acidic sulfate aerosol, to expose BEAS-2B cells to the total isoprene SOA mixture. We then systematically explored the effects of three known composition types of isoprene-derived SOA by generating SOA through dark reactive uptake experiments by starting with key gaseous intermediates, including trans-beta-isoprene epoxydiol (trans-beta-IEPOX), methacrylic acid epoxide (MAE), or isoprene hydroxyhydroperoxides (ISOPOOH). Chemical characterization coupled with biological analyses show that atmospherically-relevant compositions of isoprene-derived SOA alter the levels of 41 oxidative stress-related genes. Of the different composition types of isoprene-derived SOA, MAE-derived SOA altered the greatest number of genes. Taken together, the different composition types accounted for 34 of the genes altered by the total isoprene SOA mixture while 7 remained unique to the total mixture exposures indicating that there is either a synergistic effect of the different isoprene-derived SOA components or an unaccounted component in the mixture. Importantly, this work reveals an enrichment for altered expression of genes transcriptionally controlled by Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in cells exposed to all types of isoprene-derived SOA. The enrichment of the Nrf2 pathway may indicate a response to inflammation initiated by isoprene SOA exposure. The findings from this initial exploration emphasize the importance of future in-vitro and in-vivo work to inform policy not only because of the atmospheric abundance of isoprene-derived SOA, but also because the anthropogenic contribution is the only component amenable to control.Doctor of Philosoph