Gene Expression and Target Tissue Dose in the Rat Epidermis after Brief JP-8 and JP-8 Aromatic and Aliphatic Component Exposures

• Published in: Toxicological sciences 2007-06, Vol.97 (2), p.569-581
• Main Authors: McDougal, James N., Garrett, Carol M.
• Format: Article
• Language: English
• Subjects: aliphatic hydrocarbons; Animals; Apoptosis - drug effects; aromatic hydrocarbons; Cell Proliferation - drug effects; cutaneous exposure; Data Interpretation, Statistical; epidermis; Epidermis - cytology; Epidermis - drug effects; Epidermis - metabolism; gene expression; Gene Expression - drug effects; Growth - drug effects; Growth - genetics; Hydrocarbons - toxicity; Hydrocarbons, Aromatic - toxicity; Inflammation - chemically induced; Inflammation - pathology; Irritants; JP-8 jet fuel; Male; Oligonucleotide Array Sequence Analysis; rat; Rats; Rats, Inbred F344; Reverse Transcriptase Polymerase Chain Reaction; RNA - biosynthesis; RNA - genetics; Signal Transduction - drug effects; Skin - chemistry; Skin - metabolism; skin irritation
• ISSN: 1096-6080; 1096-0929
• DOI: 10.1093/toxsci/kfm037

Exposures of jet propulsion fuel 8 (JP-8) to human and laboratory animal skin have 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 (UND), tetradecane (TET), trimethylbenzene (TMB), and dimethylnaphthalene (DMN) for 1 h and examined 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. UND and TMB exposures caused the greatest number of changes in transcript levels compared to DMN and TET. 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 mimicked the gene expression resulting from the JP-8 exposure but that UND had the most similar responses. These data suggest that there are differences in potency between the four components studied.