Cellular effects of subway air particles in human lung cells

项目总结/文摘

PROJECT SUMMARY/ABSTRACT This project will compare indoor air quality at three underground subway stations in Philadelphia with the corresponding aboveground urban locations as well as one suburban location. We found previously that PM levels in Philadelphia subway stations can be up to five times higher than levels on an urban street. We will assess effects of particulate matter (PM) from the various locations on lung epithelial cells (16HBE and primary cells), assessing cytotoxicity, oxidative stress, and the cellular response pathways involving the antioxidant response element (ARE) and the xenobiotic response element (XRE). A primary purpose is to assess the contributions of various PM components to these cellular responses. In Aim 1, we will collect 102 total samples from the various locations and determine to what extent levels of black carbon (BC), ultrafine particles (UFP), and metals correlate with the cellular effects. Both BC and UFP have been associated with cellular oxidative stress. Subway PM is particularly high in metals such as iron, copper, antimony and zinc, which come from the rails, wheels, brake pads, and other parts of the trains, which have been correlated with oxidative stress and ARE activation from other PM sources. In Aim 2, we will examine the role of soluble/chelatable metals compared to metals in whole particles on the cellular effects, as well assess contributions from organic compounds on these effects. As part of this work, we will probe the contributions of the XRE and ARE pathways to the cellular effects by using siRNA against the relevant sensors/transcription factors, aryl hydrocarbon receptor (AhR) and Nrf2, respectively. Dose response curves will be used to assess effects over a range of concentrations. Results will help in understanding and ideally mitigating the health risks of subway air particles. We have assembled a multidisciplinary team of researchers, including experts in air particulate analysis, cellular oxidative stress, statistical analysis, and analytical metal analysis, and an inhalation toxicologist at the EPA. The project includes ten undergraduate student positions working in three different departments at Villanova and two summer positions at an EPA lab. Students will be primary drivers of the work, its interpretation, and presentation at national conferences and authors on published work.