Excitement in Vesicant Research -- Yesterday, Today and Tomorrow
Abstract
The presentation focuses on the biochemical and cellular mechanisms that may be responsible for the development of the acute cutaneous sulfur mustard (HD) injury and their exploitation for establishing rational approaches for therapeutic intervention. Relevant background information identifies the known, toxicologically important chemical reactions of HD with cellular targets and describes the pathological events that lead to vesication. The penultimate event in the formation of large subepidermal blisters appears to be the premature massive, and almost concurrent death of basal epidermal keratinocytes with release of injury-producing proteases and inflammatory mediators. The genotoxicity of HD--the major thrust of HD research for more than 40 years, and one that has made major contributions to our knowledge of molecular genetics--is briefly described. Evidence suggests, however, that a potent genotoxicity of HD does not play a causal role in the acute cutaneous HD injury. Tissue injury requires higher doses than does genotoxicity, takes less time to develop, and is not dependent on DNA cross-links. Next, the currently proposed hypotheses for HD cytotoxicity are described. Calmodulin antagonists, which were reported to protect against thermal burns, frostbite, and other selected skin injuries, are discussed as potential common vesicant antidotes.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 13, 1993
- Accession Number
- ADP008752
Entities
People
- Bruno Papirmeister