USE OF A STRATIFIED OXIDATIVE STRESS MODEL TO STUDY THE BIOLOGICAL EFFECTS OF AMBIENT CONCENTRATED AND DIESEL EXHAUST PARTICULATE MATTER

Abstract

Although several epidemiological studies have shown a positive relationship between exposure to ambient air particulate matter (PM) and adverse health effects in humans, there is still a fundamental lack of understanding of the most toxic particle components and the biological mechanisms through which they act. Since our studies on the biological effects of diesel exhaust particles (DEP) have highlighted the role of reactive oxygen species (ROS), catalyzed by organic chemical compounds, we set out to establish whether this constitutes an oxidative stress model that can be used to study the biological effects of ambient coarse and fine PM. We demonstrate that organic DEP extracts induce a stratified oxidative stress response, leading to heme oxygenase 1 (HO-1) expression at normal GSH/ GSSG ratios, proceed to Jun kinase activation and interleukin 8 (IL-8) production at intermediary oxidative stress levels, and culminate in cellular apoptosis in parallel with a sharp decline in GSH/GSSG ratios. We demonstrate that ambient concentrated air particulates, collected with a particle concentrator and a liquid impinger, mimic the effects of organic DEP extracts at lower oxidative stress levels. While fine PM consistently induced HO-1 expression in all most of the samples collected over a 9-mo survey period, coarse particulates were effective at inducing that effect during fall and winter. Moreover, HO-1 expression was positively correlated to the higher organic carbon (OC) and polyaromatic hydrocarbons (PAHs) content of fine versus coarse PM, as well as the rise in PAH content that occurs in coarse PM during the winter months. Although coarse and fine PM lead to a decrease in cellular glutathione (GSH)/GSSG ratios, oxidative stress did not increase to cytotoxic levels. Taken together, these data demonstrate that it is possible to use the stratified oxidative stress model developed for DEP to interpret the biological effects of coarse and fine PM. This work has important implications for the selection of relevant biological endpoints for in vivo studies.