Proteomic analysis of simulated occupational jet fuel exposure in the lung

We analyzed protein expression in the cytosolic fraction prepared from whol e lung tissue in male Swiss-Webster mice exposed 1 h/day for seven days to aerosolized JP-8 jet fuel at concentrations of 1000 and 2500 mg/m(3), simul ating military occupational exposure. Lung cytosol samples were solubilized and separated via large scale, high resolution two-dimensional electrophor esis (2-DE) and gel patterns scanned, digitized and processed for statistic al analysis. Significant quantitative and qualitative changes in tissue cyt osol proteins resulted from jet fuel exposure. Several of the altered prote ins were identified by peptide mass fingerprinting, confirmed by sequence t ag analysis, and related to impaired protein synthetic machinery, toxic/met abolic stress and detoxification systems, ultrastructural damage, and funct ional responses to CO2 handling, acid-base homeostasis and fluid secretion. These results demonstrate a significant but comparatively moderate JP-8 ef fect on protein expression and corroborate previous morphological and bioch emical evidence. Further molecular marker development and mechanistic infer ences from these observations await proteomic analysis of whole tissue homo genates and other cell compartment, ie., mitochondria, microsomes, and nucl ei of lung and other targets.