Showing papers by "John J. Schlager published in 2005"

Microarray analysis of gene expression in murine skin exposed to sulfur mustard

Abstract: The chemical warfare agent sulfur mustard [bis-(2-chloroethyl)-sulfide; SM] produces a delayed inflammatory response followed by blister formation in skin of exposed individuals Studies are underway evaluating the efficacy of pharmacological compounds to protect against SM skin injury Microarray analysis provides the opportunity to identify multiple transcriptional biomarkers associated with SM exposure This study examined SM-induced changes in gene expression in skin from mice cutaneously exposed to SM using cDNA microarrays Ear skin from five mice, paired as SM-exposed right ear and dichloromethane vehicle-exposed left ear at six dose levels (0005, 001, 002, 004, 008, and 016 mg; 6 mM to 195 mM range), was harvested at 24 h post-exposure SM-induced gene expression was analyzed using cDNA microarrays that included 1,176 genes Genes were selected on the basis of all mice (N = 5) in the same dose group demonstrating a ≥2-fold increase or decrease in gene expression for the SM-exposed tissue compared to the dichloromethane vehicle control ear tissue at all six SM doses When skin exposed to all six concentrations of SM was compared to controls, a total of 19 genes within apoptosis, transcription factors, cell cycle, inflammation, and oncogenes and tumor suppressors categories were found to be upregulated; no genes were observed to be downregulated Differences in the number and category of genes that were up- or down-regulated in skin exposed to low (0005–001 mg) and high (008–016 mg) doses of SM were also observed The results of this study provide a further understanding of the molecular responses to cutaneous SM exposure, and enable the identification of potential diagnostic markers and therapeutic targets for treating SM injury © 2005 Wiley Periodicals, Inc J Biochem Mol Toxicol 18:289–299, 2004; Published online in Wiley InterScience (wwwintersciencewileycom) DOI 101002/jbt20043

Time- and dose-dependent analysis of gene expression using microarrays in sulfur mustard-exposed mice.

Abstract: The chemical warfare agent sulfur mustard (SM) produces blister formation with a severe inflammatory reaction in skin of exposed individuals. The development of efficacious countermeasures against SM vesication requires an understanding of the cellular and molecular mechanism of SM-induced tissue injury. This study examined SM-induced alterations in gene expression using Atlas Mouse 5K DNA microarrays (5002 genes) to identify transcriptional events associated with SM skin injury. Mice (N=3) were exposed topically to SM (0.04, 0.08, and 0.16 mg; 48.8, 97.5, and 195 mM) on the inner surface of the right ear and skin tissues were harvested at 1.5, 3, 6, and 12 h. Genes were selected based on the three mice in the same dose group demonstrating a > or =2-fold increase or decrease in gene expression for the SM-exposed tissue when compared to the dichloromethane vehicle control ear at all three doses and four time points. At the 0.04 mg SM dose, the genes observed were primarily involved in inflammation, apoptosis, and cell cycle regulation. Exposure to 0.08 mg SM increased the expression of genes related to inflammation and cell cycle regulation. Exposure to 0.16 mg SM led to a total of six genes that were changed at all observed time periods; however, these genes do not appear to be directly influential in biological mechanisms such as inflammation, apoptosis, and cell cycle regulation as was observed at the lower SM doses of 0.04 and 0.08 mg. These functional categories have been observed in previous studies utilizing both in vivo and in vitro model systems of SM-induced dermal injury, suggesting that molecular mechanisms associated with inflammation, apoptosis, and cell cycle regulation may be appropriate targets for developing prophylactic/therapeutic treatments for SM skin injury.