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ToxSci Advance Access published online on November 3, 2006
Toxicological Sciences, doi:10.1093/toxsci/kfl154
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© The Author 2006. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received September 21, 2006
Accepted October 27, 2006

Systems Toxicology

Effects of Brief Cutaneous JP-8 Jet Fuel Exposures on Time-Course of Gene Expression in the Epidermis

James N. McDougal 1 *, Carol M. Garrett 1, Carol M. Amato 1, and Steven J. Berberich 2

1 Wright State University, Dept of Pharmacology & Toxicology, Dayton, OH, United States
2 Wright State University, Department of Biochemistry and Molecular Biology, Dayton, OH, USA

* To whom correspondence should be addressed.
James N. McDougal, E-mail: james.mcdougal{at}wright.edu


  Abstract

The jet fuel, JP-8, has been shown to cause an inflammatory response in the skin, which is characterized histologically by erythema, edema and hyperplasia. Studies in laboratory animal skin and cultured keratinocytes have identified a variety of changes in protein levels related to inflammation, oxidative damage, apoptosis and cellular growth. Most of these studies have focused on prolonged exposures and subsequent effects. In an attempt to understand the earliest responses of the skin to JP-8, we have investigated changes in gene expression in the epidermis for up to 8 hours after a one-hour cutaneous exposure in rats. After exposure, we separated the epidermis from the rest of the skin with a cryotome and isolated total mRNA. Gene expression was studied with microarray techniques and changes from sham-treatments were analyzed and characterized. We found consistent two-fold increases in gene expression of 27 transcripts at one, four and eight hours after the beginning of the one-hour exposure that were related primarily to structural proteins, cell signaling, inflammatory mediators, growth factors and enzymes. Analysis of pathways changed showed that several signaling pathways were increased at one hour and that the most significant changes at eight hours were in metabolic pathways, many of which were downregulated. These results confirm and expand many of the previous molecular studies with JP-8. Based on the one-hour changes in gene expression, we hypothesize that the "trigger" of the JP-8-induced, epidermal, stress response is a "physical" disruption of osmotic, oxidative and membrane stability which activates gene expression in the signaling pathways and results in the inflammatory, apoptotic and growth responses that have been previously identified.


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