Identification of target genes responsive to JP-8 exposure in the rat central nervous system.
Concern for the health risk associated with occupational exposure to jet fuel has emerged in the Department of Defense. Jet propulsion fuel-8 (JP-8) is the fuel used in most US and North Atlantic Treaty Organization (NATO) jet aircraft, and will be the predominant fuel both for military land vehicles and aircraft into the twenty-first century. JP-8 exhibits reduced volatility and lower benzene content as compared to JP-4, the predominant military aircraft fuel before 1992, possibly suggesting greater occupational exposure safety. However, the higher rates of occupational exposure through fueling and maintenance of increasingly larger numbers of aircraft/vehicles raise concerns with respect to toxicity. Clinical studies of workers experiencing long-term exposure to certain jet fuels demonstrated deficits in CNS function, including fatigue, neurobehavioral changes, psychiatric disorders, and abnormal electroencephalogram (EEG). In the present study, cDNA nylon arrays (Atlas Rat 1.2 Array, Clontech Laboratories, Palo Alto, CA) were utilized to measure changes in gene expression in whole brain tissue of rats exposed repeatedly to JP-8, under conditions that simulated possible real-world occupational exposure (6 h/day for 91 days) to JP-8 vapor at 1,000 mg/m3. Gene expression analysis of the exposure group compared to the control group revealed a modulation of several genes, including glutathione S-transferase Yb2 subunit (GST Yb2); cytochrome P450 IIIAl (CYP3A1); glucose-dependent insulinotropic peptide (GIP); alpha1-proteinase inhibitor (alpha1-AT); polyubiquitin; GABA transporter 3 (GAT-3); and plasma membrane Ca2+-transporting ATPase (brain isoform 2) (PMCA2). The implications of these vapor-induced changes in gene expression are discussed.
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Center for Bio/Molecular Science & Engineering, Code 6900, Naval Research Laboratory, Washington, District of Columbia 20375, USA.
Ritchie
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Rossi
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Pancrazio
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D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis; D001921:Brain / Q000502:physiology; D002490:Central Nervous System / Q000187:drug effects; D051544:Cytochrome P-450 CYP3A; D005749:Gastric Inhibitory Polypeptide / Q000096:biosynthesis; D020869:Gene Expression Profiling; D005982:Glutathione Transferase / Q000096:biosynthesis; D006838:Hydrocarbons / Q000009:adverse effects*; D008297:Male; D008889:Military Personnel; D016273:Occupational Exposure; D020411:Oligonucleotide Array Sequence Analysis; D011480:Protease Inhibitors / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013723:Teratogens / Q000633:toxicity*; D014835:Volatilization
D006838:Hydrocarbons; C098607:JP8 aviation fuel; D011480:Protease Inhibitors; D013723:Teratogens; D005749:Gastric Inhibitory Polypeptide; D001189:Aryl Hydrocarbon Hydroxylases; C465138:Cyp3a23-3a1 protein, rat; D051544:Cytochrome P-450 CYP3A; D005982:Glutathione Transferase