THE EFFECTS OF SULFUR MUSTARD ON TRANSCRIPTION IN HUMAN EPIDERMAL KERATINOCYTES: ANALYSIS AT EARLY TIME POINTS THROUGH DNA ARRAYS

A common experimental approach designed to elucidate biochemical mechanisms of action of disease states and toxicological insults is to systematically identify the differentially expressed genes between a particular cell state and control. Currently, there are a range of commonly used molecular toxicology methods that permit global differential gene expression studies (e.g., messenger ribonucleic acid (mRNA) differential display; subtractive hybridization; suppression polymerase chain reaction; serial analysis of gene expression). However these studies usually are expensive and labor-intensive, and they often are difficult. The recent innovation and commercial availability of deoxyribonucleic acid (DNA) arrays can allow researchers to gather similar fundamental information by the methods mentioned above, but with considerably less cost, time, and difficulty. This study describes how DNA arrays were screened to generate an overview of the differential gene expression changes that occur within human epidermal keratinocytes after exposure to sulfur mustard (SM). Specifically, the gene expression pattern of healthy cells was compared directly to those exposed to vesicating concentrations of SM for 10 or 30 milt. These time courses were examined since the SM-mediated injury process is attributed to irreversible events that occur within minutes of exposure. Several genes were identified that exhibited significant transcriptional upregulation and could have key roles in the early SM injury. These include the serine protease hepsin, the transcription factor STAT6, and the integral membrane protein heparin, sulfate proteoglycan 2.