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Published ahead of print on December 23, 2004, doi:10.1165/rcmb.2004-0171OC
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American Journal of Respiratory Cell and Molecular Biology. Vol. 32, pp. 192-200, 2005
© 2005 American Thoracic Society
DOI: 10.1165/rcmb.2004-0171OC

Altered Expression of {gamma}-Synuclein and Detoxification-Related Genes in Lungs of Rats Exposed to JP-8

Luis A. Espinoza, Mohammad Valikhani, María J. Cossio, Theresa Carr, Mira Jung, Juanita Hyde, Mark L. Witten and Mark E. Smulson

Department of Biochemistry and Molecular Biology, and Department of Radiation Medicine, Georgetown University School of Medicine, Washington, DC; and Joan B. and Donald R. Diamond Lung Injury Laboratory, Department of Pediatrics, Arizona Health Sciences Center, Tucson, Arizona

Correspondence and requests for reprints should be addressed to Dr. Mark Smulson, Department of Biochemistry and Molecular Biology, Georgetown University School of Medicine, 3900 Reservoir Road NW, Washington, DC 20057. E-mail: smulson{at}georgetown.edu

Many military personnel are at risk of lung damage or systemic toxicity as a result of exposure to the jet fuel JP-8. We have now used microarray analysis to characterize changes in the gene expression profile of lung tissue induced by exposure of rats to JP-8 at a concentration of 171 or 352 mg/m3 for 1 h/d for 7 d, with the higher dose estimated to mimic the level of occupational exposure in humans. The expression of 56 genes was significantly affected by a factor of <= 0.6 or >= 1.5 by JP-8 at the low dose. Eighty-six percent of these genes were downregulated by JP-8. The expression of 66 genes was similarly affected by JP-8 at the higher dose, with the expression of 42% of these genes being upregulated. Prominent among the latter genes was that for the centrosome-associated protein {gamma}-synuclein, whose expression was consistently increased. The expression of various genes related to antioxidant responses and detoxification, including those for glutathione S-transferases and cytochrome P450 proteins, were also upregulated. The microarray data were confirmed by quantitative RT-PCR analysis. Our extensive data set may thus provide important insight into the pulmonary response to occupational exposure to JP-8 in humans.

Key Words: JP-8 jet fuel • oligonucleotide microarrays • immunohistochemistry • {gamma}-synuclein • quantitative RT-PCR




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