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COMPARATIVE IN VITRO CARDIAC TOXICITY OF PRIMARY COMBUSTION PARTICLES: IDENTIFICATION OF CAUSAL CONSTITUENTS AND MECHANISMS OF INJURY
Citation:
Dreher, K L. AND T. Knuckles. COMPARATIVE IN VITRO CARDIAC TOXICITY OF PRIMARY COMBUSTION PARTICLES: IDENTIFICATION OF CAUSAL CONSTITUENTS AND MECHANISMS OF INJURY. Presented at American Thoracic Society, San Diego, CA, May 20 - 25, 2005.
Description:
Identification of causal particle characteristics and mechanisms of injury would allow linkage of particulate air pollution adverse health effects to sources. Research has examined the direct cardiovascular effects of air pollution particle constituents since previous studies demonstrated a rapid increase in particle bioavailable constituents within the plasma of rats following pulmonary deposition of combustion particles. Cardiomyocyte (CM) from 1 day old rat pups were exposed to various doses of either aqueous or organic particle-free leachates (Ls) obtained from different residual oil fly ash (ROFA), coal fly ash (CFA), or diesel exhaust particles (DEP). CM cytotoxicity and functional effects were monitored by lactate dehydrogenase (LDH) release and changes to spontaneous beating frequency, respectively. Only aqueous ROFA-Ls were cytotoxic to CMs at concentrations >3 �g/ml and was not mediate by major ROFA metal constituents. Oxidative stress was found to be a causal mechanism for cytotoxicity at high but not low ROFA-L doses. Only aqueous ROFA-Ls produced (+) chronotropic effects on CMs which could be reproduced by a V+Fe+Ni mixture. Only organic DEP-Ls were cytotoxic to CMs at concentrations >12 �g/ml. Aqueous and organic DEP-Ls produced (-) chrontropic effects on CMs. However, organic DEP-L was more potent in altering CM beating frequency which could be attributed to its hydrophilic organic constituents. Aqueous and organic leachates of fine (PM<2.5) CFA had no effect on CM cytotoxicity or function. An organic extract of ultrafine CFA was not cytotoxic to CM but did produce (-) chronotropic effects. Comparison of the data revealed the hierarchy of combustion particle cardiotoxicity to be: ROFA>DEP>CFA. These data demonstrate that different combustion particles elicit different effects on CMs which can be linked to their physicochemical properties. (This abstract does not reflect EPA policy)