Expression profiling of sulfur mustard exposure in murine skin: Chemokines, cytokines, and growth factors

The chemical warfare agent sulfur mustard (SM) produces a delayed inflammatory response followed by blister formation in skin of exposed individuals. Severity and time to onset of inflammation and tissue damage vary greatly and depend on various factors such as dose, ambient temperature, and exposure site. Gene arrays provide the opportunity to identify multiple transcriptional events associated with low-level exposure SM. This study examined SM-induced changes in gene expression in skin from mice cutaneously exposed to SM using cDNA arrays. Skin from 5 mice, paired as SM-exposed right ear and unexposed left ear at six dose levels (0.005, 0.01, 0.02, 0.04, 0.08, and 0.16 mg) was harvested at 24 hours post-exposure. The lowest concentration (0.005 mg) produced no apparent tissue damage. The highest SM dose (0.16 mg) produced severe injury characterized by edema, dermal infiltration of inflammatory cells, premature death of basal layer epidermal cells, and epidermal-dermal separation. We analyzed SM-induced genes using cDNA microarray technology, which included 1,176 genes. The genes were classified in six categories. Chemokines, cytokines and growth factors represented a large number of the genes altered with SM exposure. A number of these genes not known to be associated with SM toxicity were identified. The results provide not only a new molecular basis for understanding the response to SM, but also a useful resource for future development of diagnostic markers and therapeutic targets for SM injury.