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Association Between ROS on Ambient PM2.5 and Cardiovascular Effects in a Controlled Human Exposure Study
Citation:
Devlin, R., V. Verma, A. Rappold, H. Tong, AND R. Weber. Association Between ROS on Ambient PM2.5 and Cardiovascular Effects in a Controlled Human Exposure Study. Society of Toxicology, New Orleans, LA, March 13 - 17, 2016.
Impact/Purpose:
OAR has as a research need for a better understanding of the mechanisms by which particulate matter (PM) air pollution causes adverse health effects. This abstract describes research that shows reactive oxygen species (ROS) present on PM are better associated with health effects than PM mass. It also shows that different types of ROS are associated with different health end points.
Description:
Several studies have shown that inhalation of PM can induce oxidative stress on target organs or tissues. However, it is not clear whether that stress is caused by ROS generated from particles or by the ability of inhaled particles to contribute to the formation of endogenous intracellular or extracellular oxidative stress. To assess the ability of particle-associated ROS to cause biologic changes in humans, DTT activity (a measure of ROS) was quantified in water soluble and methanol soluble material extracted from Teflon filters that captured PM mass during a study in which humans were exposed to concentrated ambient air particles (CAPS). Twenty-nine volunteers were exposed for two hours on two occasions: once to clean air and once to fine + ultrafine CAPS. Linear mixed effects models with subject specific random intercept were used to test changes in effects between the CAPS and air exposures. Robust associations were observed between both PM mass and particle number and changes in endothelial cell function, HRV, cardiac repolarization, blood lipids, and cellular and soluble vascular markers. Water soluble PM was extracted from 47 mm Teflon filters collected during the CAPS exposures by sonication in deionized water for 1 hr. A portion of the extract was used to measure total DTT content. A portion was passed through a C-18 column, which binds hydrophobic material. The material passing through the column (hydrophilic material) was assayed for DTT activity. The hydrophobic DTT activity was determined by difference. A portion of the filter was also extracted in methanol. We compared the association between particle generated ROS and health end points. Changes in endothelial function were associated with total DTT, hydrophilic DTT and hydrophobic DTT activity. Changes in cardiac QT interval were associated with the total and hydrophilic DTT fraction. Changes in blood lipids and cells were associated with the methanol DTT fraction. We conclude that particle-associated DTT activity is strongly associated with biologic end points altered by PM exposure and that different DTT fractions are associated with different groups of biological end points. This abstract of a proposed presentation does not represent EPA policy.