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CYTOTOXICITY AND CELL SIGNALING IN MH-S CELLS: RELATIVE POTENCY OF DIESEL AND COAL COMBUSTION PARTICLES
Citation:
Singh, P., Y. Kostetski, M. J. Daniels, T. Stevens, AND M I. Gilmour. CYTOTOXICITY AND CELL SIGNALING IN MH-S CELLS: RELATIVE POTENCY OF DIESEL AND COAL COMBUSTION PARTICLES. Presented at Society of Toxicology, Baltimore, MD, March 21-25, 2004.
Description:
Cytotoxicity and Cell Signaling in MH-S Cells: Relative Potency of Diesel and Coal Combustion Particles P. Singh1, Y. Kostetski2, M. Daniels1, T. Stevens3 and MI Gilmour 1USEPA, RTP, NC, 2National University of Singapore, Singapore, 3University of North Carolina, Chapel Hill, NC
Pulmonary exposures to combustion source particulate matter (PM) are known to induce inflammatory lung diseases, however it is not well understood how these particles exert their effects and how different sources and types of PM rank in potency. We have previously demonstrated in mice that diesel exhaust particles (DEP) high in organic carbons produced macrophage influx, while DEP, high in elemental carbon, induced neutrophilic inflammation in the lung. In the present study we tested the in vitro effects of these DEP (SRM-DEP, A1-DEP) along with a third DEP sample (A2-DEP) and two coal particulate samples (M-Coal, K-Coal) on ATP levels and necrosis as well as JNK and p38 MAP kinase activation in a mouse alveolar macrophage cell line. The particulate samples were analyzed by electron paramagnetic resonance (EPR) to determine whether surface free radical concentrations were associated with cytotoxicity or bioactive potency. All particle treatments produced a dose-dependent decrease in ATP levels at 1, 4, and 24 h post exposure, however the relative potencies of the different samples were distinct: SRM-DEP = A2-DEP > A1-DEP > M-Coal = K-Coal. All particle-exposed cells showed significant increases in necrosis above control levels at 24 h. A2-DEP stimulated the earliest increase in phosphorylated p38 MAP kinase, while A1-DEP induced a later but far more dramatic rise. A1-DEP was also the most potent stimulator of phosphorylated JNK in these cells. EPR analysis showed that SRM-DEP had the highest concentration of surface free radicals followed by A2-DEP, which had about half and A1-DEP, which had about 1/10 the activity. These results indicate that surface free radical concentration is related to a reduction in ATP levels. However, the relative potency of activation was not associated with levels of surface free radicals, suggesting that mechanisms of PM-induced cellular activation and injury are distinct. (This abstract does not reflect EPA policy.)