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DETECTION AND MOLECULAR ANALYSIS OF PARTICULATE AIR POLLUTION INDUCED CARDIOPULMONARY OXIDATIVE STRESS USING A TRANSGENIC MOUSE MODEL AND EMERGING TECHNOLOGIES
Citation:
Dreher, K L., E. S. Roberts, S. Malstrom, AND A. Malekafzali. DETECTION AND MOLECULAR ANALYSIS OF PARTICULATE AIR POLLUTION INDUCED CARDIOPULMONARY OXIDATIVE STRESS USING A TRANSGENIC MOUSE MODEL AND EMERGING TECHNOLOGIES. Presented at Society of Toxicology Annual Meeting, New Orleans, LA, March 06 - 10, 2005.
Description:
Identification of particle characteristics and biological mechanism(s) responsible for the adverse pulmonary and cardiovascular responses associated with particulate air pollution exposure remains a critical research activity. We have employed an oxidative stress sensitive and bioluminescent reporter transgenic mouse model, hemeoxygenase-1 (HO-1) luciferase, in order to identify in situ induction of oxidative stress within lung and heart tissues following pulmonary aspiration (50 ?g/50 ?l/mouse) of a suspension of residual oil fly ash (ROFA) particles. HO-1 induction in lung and heart tissue protein extracts was measured by chemiluminescence at various times following exposure. Pulmonary and cardiac chemiluminescence increased at 2h (p<0.001) and 24h (p<0.05) post-exposure, respectively. Increased chemiluminescence in lung tissue protein extracts correlated with elevated levels of luciferase protein. Bioluminescent staining of lung and heart frozen tissue sections demonstrated localized areas of oxidative stress. RNA was recovered from these regions of interest following laser capture microdissection. Gene expression profiling by microarray analysis of recovered RNA is currently ongoing and will be presented. These results demonstrate the ability of air pollution particles derived from oil combustion to induce local and systemic oxidative stress which in turn may result in acute organ injury as well as potentially contribute to disease processes that have oxidative stress and injury as common pathological etiologies. (This abstract does not reflect EPA policy)