Altered expression of gamma-synuclein and detoxification-related genes in lungs of rats exposed to JP-8.
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/m(3) 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.
Espinoza
Luis A
LA
Department of Biochemistry and Molecular Biology, Georgetown University School of Medicine, 3900 Reservoir Road NW, Washington, DC 20057, USA.
Valikhani
Mohammad
M
Cossio
María J
MJ
Carr
Theresa
T
Jung
Mira
M
Hyde
Juanita
J
Witten
Mark L
ML
Smulson
Mark E
ME
D000395:Air Pollutants, Occupational / Q000494:pharmacology*; D000818:Animals; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D006838:Hydrocarbons / Q000494:pharmacology*; D007150:Immunohistochemistry; D008168:Lung / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051843:Synucleins; D051845:gamma-Synuclein
D000395:Air Pollutants, Occupational; D006838:Hydrocarbons; C098607:JP8 aviation fuel; D009419:Nerve Tissue Proteins; D051843:Synucleins; D051845:gamma-Synuclein