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Murine cDNA array expression profiling of cutaneous sulfur mustard injury

TitleMurine cDNA array expression profiling of cutaneous sulfur mustard injury
Publication TypeConference Proceedings
Year of Conference2002
AuthorsSabourin C.L., Choi Y.W., Stonerock M.K., Casbohm S.L., Gillespie R.A., Waugh J.D., Kiser R.C., Casillas R.P., Babin M.C., Schlager J.J.
Conference NameProceedings of the 41st Annual Meeting of the Society of Toxicology
Volume66 (1-S)
PublisherOxford University Press
Conference LocationNashville, TN
KeywordsSulfur Mustard

The chemical warfare agent, sulfur mustard (SM) produces skin blister formation with a severe inflammatory reaction in exposed individuals. The mechanism of SM induced tissue injury is not well understood and there is no established medical treatment to counter its toxicity. Our previous studies identified increases in inflammatory gene expression in both in vivo and in vitro models of vesicant injury. This study examined SM-induced alterations in gene expression in mouse skin using cDNA arrays to identify transcriptional events associated with SM toxicity. Ear skin from 5 mice, paired as SM-exposed (right ear) and unexposed (left ear) from the same animal, at seven exposure doses (5, 10, 20, 40, 60, 80, and 160 mg) produced severe injury characterized by edema, dermal infiltration of inflammatory cells, premature death of basal layer epidermal cells, and epidermal-dermal separation. The lowest concentration (5 mg) produced no apparent tissue damage. Screening of 1176 cDNAs that were normalized as exposed/unexposed skin samples from the same mouse identified numerous genes activated or repressed >2 fold, with the number of altered genes increasing with SM dose. The mean level of expression (5 animals) for 54 genes increased and 78 genes decreased >2-fold at one or more exposure doses when compared to the 5 mg dose. Real-time RT-PCR confirmed the up-regulation of IL-1b and IL-6. The transcriptional activation or repression of a number of genes not previously known to be associated with SM toxicity was identified. (Supported by the US Army Medical Research and Materiel Command under Contract No. DAMD17-99-D-0010)

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