Many military and industrial personnel are exposed to JP-8 jet fuel during service and refueling of aircrafts, and maintenance of storage tanks. In toxicological studies using mice, it has been demonstrated that JP-8 can induce immunosuppression following dermal, oral, or inhalation exposures. After dermal or oral exposure to JP-8, we have previously demonstrated that thymus weight and cellularity are significantly diminished and specific IgM antibody production is suppressed by 50% or more as compared to controls. To further evaluate the effects of JP-8, this study presents comparative metabolic enzyme profiles obtained after oral or dermal exposure to JP-8. Western blotting was performed to determine the protein expression of Phase I and Phase II hepatic enzymes at 24 hours or 7 days after a 7-day exposure to JP-8. Female B6C3F1 mice were exposed to JP-8 either orally (2000 mg/kg/day) or dermally (50uL neat application). Twenty-four hours post-exposure, protein expression of CYP2E1, 2B1, GSTmu, and GSTpi, but not CYP1A1, were significantly increased in mice exposed orally to JP-8. Following a week recovery period, these enzymes returned to constitutive levels. In dermal studies, despite the presence of immunosuppression comparable to orally exposed mice, there was minimal to no induction of CYP2B1, GSTmu, and GSTpi. Current studies are underway to confirm the dermal exposure profile for CYP2E1 and CYP1A1. Additionally, histological examination of the livers from these same mice exposed orally or dermally, indicated that there was no increase in the amount of fat, hydropic degeneration or necrosis in the liver. These data suggest that the metabolism of JP-8 may not be required for immunotoxicity.
The Toxicologist. Society of Toxicology 42nd Annual Meeting and ToxExpo, Cutting-Edge Science, Networking, New Perspectives, March 9-13, 2003, Salt Lake City, Utah