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AUTHOR(S)TA 2312A2 Kabbur, M., B., Brinkley, W.W., Rogers, J.V., Gunasekar, P.G., Garrett, C.M., WU 2312A204 Geiss, K.T., McDougal, J.N.
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ABSTRACT (Maximum 200 words)Organic chemicals such as jet fuels and solvents are recognized to cause skin irritation after dermal exposure. The molecular responses to these chemicals that result in acute irritation are not understood well enough to allow the establishment and selection of safe exposure limits. We conducted studies to determine the feasibility of measuring various inflammatory mediators, including IL-I alpha, inducible nitric oxide synthase (iNOS), and nitric oxide. Male F-344 rats were dermally exposed to JP-8 jet fuel for one hour using Hill Top Chambers. Skin samples were collected at zero, one, two, four and six hours after the beginning of the exposures. Minced skin samples were frozen in liquid nitrogen and pulverized using a stainless steel pulverizer and processed for mRNA and protein analysis. Protein levels were determined using ELISA (IL-lalpha) and western blot (iNOS). Spectrophotometry was used to measure nitric oxide levels in skin using the Griess reagent. Pathological changes in the skin were evaluated histologically, and immunohistochemistry was used to localize IL-1 alpha and iNOS. Northern blot analysis revealed an increase in iNOS mRNA expression by -25% at 1 hr and -125% by 6 hr when compared to 0 hr samples. ELISA results for IL-I alpha in exposed skin samples showed increased levels from 19 to 46% over the 0 hr samples at various time points. Related, iNOS protein levels were also increased by 42 to 130%. The nitrite assay showed that levels decreased during one-hour exposure and then remained relatively constant after the exposure. Immunohistochemical staining indicated increased expression of IL-1 alpha and nitric oxide synthase compared to 0 hr samples.