Accession Number : ADP008769

Title :   Dosimetry of Exposure to Sulfur Mustard of Human Skin: Immunofluorescence Microscopy of DNA-Adducts.

Corporate Author : PRINS MAURITS LABORATORIUM TNO RIJSWIJK (NETHERLANDS)

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

Report Date : 13 MAY 1993

Pagination or Media Count : 10

Abstract : The recent use and the present-day threat of use of sulfur mustard (HD) in the Middle East stress the need of unequivocal and sensitive methods to establish whether casualties have been exposed to HD. Moreover, a satisfactory treatment is not available for injuries caused by exposure to HD. In recent years, monoclonal antibodies have been raised against a major HD-DNA adduct, i.e. N7-(2'-hydroxyethylthioethyl)-guanine. These antibodies have been used to develop methods for dosimetry by immunofluorescence microscopy of adducts to DNA after exposure to HD. This technique might be of great help for diagnosis of exposure. We were able to demonstrate, by means of immunofluorescence microscopy, the presence of the N7-guanine monoadduct in human skin biopsies exposed to Ct-values of HD vapor that do not cause blister formation. The lower detection limit in human blood is 0.3 microns HD. As expected, removal of HD-DNA adducts was observed in mouse skin in vivo and in human skin transplanted on nude mice. Surprisingly, no removal of HD-DNA adducts was observed, both in human white blood cells in vitro and in human skin exposed to HD ex vivo and postincubated at 37 deg C in tissue culture medium, even up to three days after exposure. A method is under development to detect cell-specific HD-DNA-adduct formation and removal in the various skin cells. A computer program has been developed that allows to measure the HD-adduct fluorescence in either the suprabasal or the basal cells, distinguished by cell-type specific immunochemical staining. Such techniques will facilitate investigations on the healing of skin injuries.

Descriptors :   *DOSIMETRY, *HD AGENT, *EXPOSURE(PHYSIOLOGY), *SKIN(ANATOMY), *DEOXYRIBONUCLEIC ACIDS, ANTIBODIES, BIOPSY, BLOOD, BLOOD CELLS, CASUALTIES, CELLS(BIOLOGY), COMPUTER PROGRAMS, COMPUTERS, DETECTION, FLUORESCENCE, GUANINE, HEALING, HUMANS, LEUKOCYTES, MICE, MICROSCOPY, MIDDLE EAST, MONOCLONAL ANTIBODIES, REMOVAL, SULFUR, THREATS, TISSUE CULTURE, VALUE, VAPORS, WOUNDS AND INJURIES, IMMUNOCHEMISTRY, TOXICITY.

Subject Categories : Chemical, Biological and Radiological Warfare
      Toxicology
      Biochemistry

Distribution Statement : APPROVED FOR PUBLIC RELEASE