(544c) Dose-Dependent Intracellular Reactive Oxygen and Nitrogen Species Production from Particulate Matter Exposure: Results from Ambient Samples and Chamber Experiments

Epidemiological studies have found associations between elevated particulate matter (PM) concentrations and increased incidences of cardiovascular and respiratory diseases. PM-induced oxidative stress has been suggests as a possible mechanism leading to these health effects. Here we present chemical and cellular oxidant measurements from ambient PM samples and controlled chamber experiments. We investigated reactive oxygen and nitrogen species (ROS/RNS) production from ambient PM samples and laboratory-generated secondary organic aerosols (SOA). Ambient samples (n = 104) were collected during multiple seasons from rural and urban sites around the greater Atlanta area as part of the Southeastern Center for Air Pollution and Epidemiology (SCAPE). SOA were generated from the photooxidation of six commonly emitted volatile organic compounds (VOCs). These experiments were conducted in the Georgia Tech Environmental (GTEC) facility under both dry and humid conditions in the presence of ammonium sulfate seed using H₂O₂ as an OH radical precursor. Murine alveolar macrophages were used to measure intracellular ROS/RNS production, while dithiothreitol (DTT) was used to quantify the concentration of redox-active species in each sample. For each sample, intracellular ROS/RNS was characterized using response parameters obtained by fitting dose-response data using the Hill equation. These response parameters (maximum response, EC₅₀, Hill slope, threshold, and area under the dose-response curve) were compared with DTT activity to determine whether chemical assays represent cellular ROS/RNS responses and with water-soluble PM components to elucidate species associated with PM-induced ROS/RNS production. From both ambient and chamber filters, we found that ROS/RNS production was highly dose-dependent, non-linear, and could not be represented by a single concentration measurement. We demonstrate that there is no simple correlation between DTT activity/PM composition and cellular ROS/RNS responses. For summer ambient samples, we found that DTT activity and organic species were significantly correlated with cellular ROS/RNS production, which motivates further studies involving PM-induced ROS/RNS production from summertime photochemically driven SOA. Finally, from chamber filters, we found that SOA generated from different precursor VOCs contained different concentrations of redox-active species and induced different levels of cellular ROS/RNS.