Accession Number : ADP008770


Title :   Immunochemical and Biochemical Analysis of Adducts to DNA and Proteins After Exposure to Sulfur Mustard


Corporate Author : PRINS MAURITS LABORATORIUM TNO RIJSWIJK(NETHERLANDS)


Personal Author(s) : Van Der Schans, G. P. ; De Jong, L. P. ; Mars-Groenendijk, R. H. ; Benschop, H. P. ; Baan, R. A.


Full Text : http://www.dtic.mil/dtic/tr/fulltext/u2/p008770.pdf


Report Date : 13 MAY 1993


Pagination or Media Count : 10


Abstract : The confirmed use of chemical agents in the Iran-Iraq conflict and the threat of their use in the recent Gulf War have stressed the need of reliable methods for detection of poisoning with such agents. We have chosen to define exposure to sulfur mustard (HD), based on immunochemical analysis of adducts of HD to DNA and proteins. These adducts are agent-specific and may be stable in vivo for several days or even for months. The detection methods described here are applied to blood samples to establish exposure and-if possible-to estimate internal dose. A major HD-DNA adduct has been identified as N'7-(2'-hydroxyethylthioethyl)-guanine. HD-DNA adducts in nucleated cells of blood treated with 2 micronsM HD are detectable with monoclonal antibodies raised against this monoadduct. recently, the immunochemical assay has been modified to an immunoslot-assay which is more reproducible because of its simplicity. Furthermore, it has at least the same detection limit as observed in the ELISA used previously. Application of immunofluorescence microscopy allows detection down to 0.3 microns M HD (see next paper of this proceedings). The same HD-DNA adduct can also be determined by means of HPLC with electrochemical detection. This method will be used for calibration of the immunochemical assays. Analogous to HD-DNA adducts, reaction products with blood proteins may be used to establish HD exposure. Since it was found that the amino-terminal valine in the a-chain of hemoglobin is alkylated after HD-exposure, the amino- terminal heptapeptide from this protein was synthesized and alkylated with HD.


Descriptors :   *BIOCHEMISTRY , *PROTEINS , *DEOXYRIBONUCLEIC ACIDS , *IMMUNOCHEMISTRY , *HD AGENT , IRAQ , DETECTION , THREATS , PERSIAN GULF , NETHERLANDS , CHEMICALS , PEPTIDES , SEQUENCES , MICROSCOPY , ESTIMATES , INTERNAL , CHEMICAL AGENTS , ANTIBODIES , ALKYLATION , CONFLICT , POISONING , CALIBRATION , SULFUR , MONOCLONAL ANTIBODIES , HEMOGLOBIN , CELLS(BIOLOGY) , IRAN , ANTIGENS , CYSTEINE , BLOOD , AMINO ACIDS , BLOOD PROTEINS.


Subject Categories : BIOCHEMISRTY
      TOXICOLOGY
      CHEMICAL, BIOLOGICAL AND RADIOLOGICAL WARFARE


Distribution Statement : APPROVED FOR PUBLIC RELEASE