AAAR 37th Annual Conference October 14 - October 18, 2019 Oregon Convention Center Portland, Oregon, USA
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Synergistic and Antagonistic Interactions Among the Particulate Matter (PM) Components for Cellular ROS activity and Cytotoxicity
YIXIANG WANG, Joseph V Puthussery, Haoran Yu, Vishal Verma, University of Illinois Urbana-Champaign
Abstract Number: 362 Working Group: From Aerosol Dosimetry and Toxicology to Health
Abstract Several studies have shown the associations of ambient particulate matter (PM) concentrations with many adverse health effects. The oxidative potential (OP) of PM is hypothesized to be one of the important parameters associated with its toxicological effects. To study the OP, researchers have used chemical approaches to mimic the reactive oxygen species (ROS) generation catalyzed by PM in the cells or the lung fluid. Many chemical assays have been applied to investigate the interactions among various PM components for the generation of ROS. However, their results haven’t been verified by the cellular assays. In this study, we have chosen three metals (Cu, Fe, and Mn) and four quinones (9,10-phenanthraquinone, 1,2-naphthoquinone, 1,4-naphthoquinone, and 5-hydroxy-1,4-naphthoquinone), that are most abundant in PM, in addition to the ambient humic-like substances (HULIS) from the real PM samples. We exposed the Chinese hamster ovary (CHO) cells to the mixtures of these components for 72 hours to assess the cytotoxicity and obtained the lethal concentration that causes 50% inhibition (LC50). Mixture toxicity index (MTI) method was used to determine the interaction. The MTI result indicates that Fe is synergistic with most quinones and HULIS in cytotoxicity. The interactions among quinones are mostly additive. To assess the contribution of OP in cytotoxicity, we further studied these interactions by an intracellular ROS assay, which demonstrate a similar pattern. Most importantly, we found a strong correlation between the intracellular ROS and LC50(R2= 0.67; N = 20), which indicates that the interaction among the PM components for cellular ROS activity is probably responsible for the observed cytotoxicity.