ToxSci Advance Access published online on March 3, 2007
Toxicological Sciences, doi:10.1093/toxsci/kfm037
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Gene Expression and Target Tissue Dose in the Rat Epidermis after brief JP-8 and JP-8 Aromatic and Aliphatic Component Exposures
Boonshoft School of Medicine, Wright State University, Dayton OH 45435
Corresponding author: James N. McDougal, Pharmacology and Toxicology, 3640 Col Glenn Hwy, Wright State University 45435, 937-775-3697, 937-775-7221 fax, james.mcdougal{at}wright.edu, carol.garrett{at}wright.edu
Received February 21, 2007; revision received February 21, 2007; accepted February 22, 2007
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Abstract |
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Exposures of JP-8 jet fuel to human and laboratory animal skin has resulted in skin irritation. JP-8 is a mixture of aromatic and aliphatic hydrocarbons, which in some cases have also been shown to be irritating to the skin. In an attempt to determine if aromatic or aliphatic components could mimic the JP-8-induced gene expression response, we exposed rats to JP-8, undecane, tetradecane, trimethylbenzene and dimethylnaphthalene for 1h and removed the epidermis to characterize the gene expression response. We also measured the concentrations of the JP-8 components in the epidermis with gas chromatography/mass spectrometry after 1-h exposures to JP-8 and pure components to determine if differences in potency could be identified. Changes in gene expression, compared to sham treatment, were studied with microarray techniques and analyzed for changes in gene ontology categories. Undecane and trimethylbenzene exposures caused the greatest number of changes in transcript levels compared to dimtheylnaphthalene and tetradecane. When only the specific functional and signaling pathways that were changed by JP-8 were considered, these pathways were nearly all activated by the components, but to different extents. After pure component exposures, the epidermal concentrations of the components showed no significant differences although the differences in magnitude of either total or pathway-specific gene expression differed by a factor of 10-fold. We conclude that no single component that we studied mimics the gene expression resulting from the JP-8 exposure, but that undecane had the most similar responses. These data suggest that there are differences in potency between the four components studied.
Key Words: Gene expression; skin irritation; JP-8 jet fuel; epidermis; cutaneous exposure; rat; aromatic hydrocarbons; aliphatic hydrocarbons.