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Published ahead of print on December 23, 2004, doi:10.1165/rcmb.2004-0171OC

Am. J. Respir. Cell Mol. Biol., Volume 32, Number 3, March 2005, 192-200

A more recent version of this article appeared on March 1, 2005
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Submitted on May 20, 2004
Revised on December 22, 2004

Altered expression of {gamma}-synuclein and detoxification-related genes in lungs of rats exposed to JP-8

Luis A Espinoza1, Mohammad Valikhani1, Maria J Cossio1, Theresa Carr2, Mira Jung2, Juanita Hyde3, Mark L Witten3, and Mark E Smulson1*

1 Department of Biochemistry and Molecular Biology, Georgetown University School of Medicine, Washington, DC, USA, 2 Department of Radiation Medicine, Georgetown University School of Medicine, Washington, DC, USA, 3 Department of Pediatrics, Arizona Health Sciences Center, Tucson, AZ, USA

* To whom correspondence should be addressed. 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 per day for 7 days, 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. 86% of these genes were down-regulated 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 up-regulated. 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 up-regulated. 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.




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