Application of Proteomics to Elucidate the Mechanism of Toxicity of the Chemical Warfare Agent Sulfur Mustard
Abstract
The complex molecular and cellular changes that occur following exposure to sulfur mustard (SM) have made it difficult to elucidate the primary mechanisms associated with SM-induced skin vesication. This report describes the use of proteomic approaches and methodologies to address this problem. Proteomic technologies, primarily two-dimensional (2D) gel electrophoresis and mass spectrometry, allow monitoring and identification of the complex molecular changes that occur in cells following toxic exposures. Cultured human epidermal keratinocytes were exposed to a vesicating dose (200 mM) of SM for up to 24 hours, the cellular proteins were extracted, and were analyzed by 2D electrophoresis. Selected differentially expressed proteins were analyzed by mass spectrometry for identification. Using this approach we have identified proteins involved in cytoskeletal structure as potential targets of SM. We are applying these techniques to identify protein pathways involved in the molecular mechanism of SM-induced vesication, and to identify potential therapeutic targets for the development of vesicant medical countermeasures.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2003
- Accession Number
- ADA418243
Entities
People
- James F. Dillman
- John J. Schlager
Organizations
- United States Army Medical Research Institute of Chemical Defense