Accession Number:

ADA273757

Title:

Verification, Dosimetry, and Biomonitoring of Mustard Gas Exposure via Immunochemical Detection of Mustard Gas Adducts to DNA and Proteins

Descriptive Note:

Final rept.,

Corporate Author:

PRINS MAURITS LABORATORIUM TNO RIJSWIJK (NETHERLANDS)

Report Date:

1993-07-01

Pagination or Media Count:

298.0

Abstract:

Convenient methods for diagnosis and dosimetry of exposure to chemical agents are not available, but are urgently needed. Immunochemical methods have now been developed for diagnosis and dosimetry of exposure to mustard gas. Exposure of calf-thymus DNA and human blood to mustard gas results in the formation of one major and two minor DNA adducts which were fully characterized. Monoclonal antibodies were raised against the major DNA adduct, i.e., the N7-guanine monoadduct. With some of these monoclonals an ELISA test was developed which detects damage in blood due to exposure to greater than or equal 2 micrometer mustard gas, presumably being at the lower limit of toxicological relevance. With the same monoclonals an immunofluorescence test was developed which detects damage in human skin due to exposure to Ct values of mustard gas vapor that do not yet cause blister formation. In order to obtain antibodies against protein adducts, the amino-terminal heptapeptide in the alpha-chain of hemoglobin was synthesized in which the amino group of the terminal valine was alkylated with mustard gas. Studies to raise antibodies against this peptide are still in progress. Since cysteine is the amino acid most susceptible to alkylation by mustard gas, a hapten containing the cysteine adduct is also being prepared.

Subject Categories:

  • Biochemistry
  • Chemical, Biological and Radiological Warfare

Distribution Statement:

APPROVED FOR PUBLIC RELEASE