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 (0.005, 0.01, 0.02, 0.04, 0.08, and 0.16 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 > or =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 (0.005-0.01 mg) and high (0.08-0.16 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.

Whole genome expression analysis in primary bronchial epithelial cells after exposure to sulphur mustard

“…The most serious effects on the respiratory system include oedema and secondary infections, both of which can be fatal (Balali-Mood and Hefazi, 2005;Kehe and Szinicz, 2005). Whilst there have been several gene expression studies after dermal exposure to SM (performed in mice and porcine models), there are no studies using microarray technology in models relevant to inhalation of SM (Dillman et al, 2006;Rogers et al, 2004;Rogers et al, 2008). This study utilised hBEC cells to address this issue, with whole genome expression analysis demonstrating significant changes in the expression of 430 genes.…”

Microarray Analysis of Mouse Ear Tissue Exposed to Bis-(2-chloroethyl) Sulfide: Gene Expression Profiles Correlate with Treatment Efficacy and An Established Clinical Endpoint

“…The systems studied include mouse ear (Sabourin et al, 2000(Sabourin et al, , 2004aRogers et al, 2004), pig skin (Sabourin et al, 2002), cultured human keratinocytes Fig. 6.…”

“…The mechanism of toxicity of SM is not well characterized, and previous studies have used DNA microarray technology to gain greater insight into the molecular pathways perturbed by SM exposure (Rogers et al, 2004;Sabourin et al, 2004a). Based on these studies, we hypothesized that gene expression profiling of mouse ear skin exposed to SM alone or pretreated with one of these treatment compounds would provide important insight into the mechanism of cutaneous toxicity of SM and might identify genes and biological pathways involved in the response to SM exposure.…”

Pathway Reconstruction of Airway Remodeling in Chronic Lung Diseases: A Systems Biology Approach

“…This investigation attempted for the first time to identify gene profiles using whole human genome microarray chips, so as to recognize potential new target molecules and pathways involved in the pathophysiology of SM-induced airway remodeling. For comparison, there have been several microarray studies on animal models involving analysis of rodent pulmonary tissue [20] and mouse skin [21] after exposure to SM.…”