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Research Topics
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 Research Topics    |    Major Focus Areas
Research Topics
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General
Project Summary

Title: Retrospective Verification of Mustard Gas Exposure
Synopsis: This study is designed to develop a blood test for mustard gas exposure, then survey individuals working with chemical agents for reproductive problems or developmental problems in their children, in order to determine if there is a relationship between mustard gas exposure and these problems.
Overall Project Objective: Determine if there is a correlation between mustard gas exposure and human reproductive and developmental problems.
Status/Results to Date: Progress since last update: In order to further investigate the role of thioether methyltransferase in mustard gas detoxification, the human cDNA encoding has been expressed at high levels in recombinant Pichia pastoris yeast which normally lack the enzyme. Recombinant yeast were shown to express the enzyme by Western immunoblotting and enzyme activity assays both in vivo and in vitro. Recombinant yeast were much more resistant to the toxicity of the mustard gas analog, 2-chloroethyl ethyl sulfide, that were normal yeast. Recombinant Pichia pastoris were also shown to methylate 2-chloroethyl sulfide on the S-atom which would prevent formation of the episulfonium which is essential to its toxicity.
Project:VA-47
Agency:Department Of Veterans' Affairs
Location:VAMC Louisville
P.I. Name:Jerald L Hoffman, Ph. D.
Research Type:Clinical
Research Focus:Chemical Weapons
Focus Category:General Health & Physical Symptoms
Status:Complete
Study Start Date:January 01,1997
Estimated Completion Date:January 31,2000
Specific Aims: 1. To establish a GC/MS method for analysis of the mustard gas adduct with the N-terminal valine of hemoglobin. 2. To analyze blood samples from Persian Gulf War veterans collected within eight months of potential exposure to chemical weapons. 3. To analyze blood samples from military personnel at the Bluegrass Army Depot collected during routine health surveillance. 4. To survey Persian Gulf War veterans and military personnel working with chemical agents for reproductive difficulties and for developmental problems in their children. 5. To search for a correlation of verified exposure to mustard gas with reproductive and developmental problems. 6. To examine cross-linked hemoglobin as a more sensitive marker of mustard gas exposure. 7. To further characterize the endogenous protection against mustard gas afforded by S-methylation by the human enzyme, thioether methyltransferase.
Methodology: 1) to establish a GC/MS method for analysis of the mustard gas adduct with the N-terminal valine of hemoglobin; 2) to analyze blood samples from Persian Gulf War veterans collected within eight months of potential exposure to chemical weapons; 3) to analyze blood samples from military personnel at the Bluegrass Army Depot collected during routine health surveillance; 4) to survey Persian Gulf War veterans and military personnel working with chemical agents for reproductive difficulties and for developmental problems in their children; and 5) to search for a correlation of verified exposure to mustard gas with reproductive and developmental problems.
Most Recent Publications:
None to date.