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GENETIC DIFFERENCES IN IN VIVO/IN VITRO AIRWAY INJURY AND INFLAMMATION AFTER OIL FLY ASH EXPOSURE
Citation:
Dye, J A., D. Andrews, J. Richards, A. King, AND U P. Kodavanti. GENETIC DIFFERENCES IN IN VIVO/IN VITRO AIRWAY INJURY AND INFLAMMATION AFTER OIL FLY ASH EXPOSURE. Presented at 2nd Inter. Conf. on Oxidative Stress and Aging, Maui, HI, April 2-5, 2001.
Description:
GENETIC DIFFERENCES IN IN VIVO/ IN VITRO AIRWAY INJURY/ INFLAMMATION AFTER OIL FLY ASH EXPOSURE
Janice Dye, Debora Andrews, Judy Richards, Annette King*, Urmila Kodavanti. US EPA & *SEE Program, RTP, NC.
Oxidative stress is implicated in the pathogenesis and progression of asthma, an inflammatory airway disease. Epidemiological studies have observed enhanced susceptibility of asthmatics to environmental particulate air pollution (PM). In vivo exposure to a "redox active" emission source PM [a vanadium-rich residual oil fly-ash (ROFA)] resulted in greater lung injury and neutrophilic inflammation in spontaneously hypertensive rats (SHR) as compared to outbred Sprague Dawley (CD) or WKY rats (background strain of SHR's). Direct airway epithelial responses to ROFA were evaluated in vitro using confluent, pseudodifferentiated rat tracheal epithelial (RTE) cultures derived from these strains. Data indicated that, relative to saline-exposed controls, ROFA exposure (5 g/cm2 x 22h) in CD-, WKY- and SHR-derived cells resulted in: (a) 1.61.8, 2.0-2.1 and 3.6-3.9 -fold increases in lactate dehydrogenase release (an indicator of cell injury) with similar increases in epithelial solute permeability; (b) decreases in intracellular glutathione (GSH) levels in the yet adherent cells by 41-43%, 39-64% and 5060%; and (c) 0-1.8, 2.1-2.8 and 5.5-13.3-fold increases in release of a neutrophil chemokine, MIP-2 (a rat IL-8 homolog), respectively. A similar trend was observed for TNFa. Strain-related differential responses were also observed in the GSH regulating enzymes, y-glutamyl-transferase (GGT) and glutathione S-transferase. Results suggest that genetic differences in airway epithelial cell antioxidant regulation or responsiveness to oxidative insult may, in part, contribute to the apparent enhanced in vivo and in vitro susceptibility of the SHR to emission source PM-induced lung health effects. (This abstract does not reflect US EPA policy.)