Accession Number : ADA310711

Title :   Protection Against the Acute and Delayed Toxicities of Sulfur Mustard.

Descriptive Note : Final rept. 4 Dec 92-3 Mar 96,

Corporate Author : MASSACHUSETTS UNIV MEDICAL SCHOOL WORCESTER

Personal Author(s) : Ludlum, David B.

PDF Url : ADA310711

Report Date : APR 1996

Pagination or Media Count : 55

Abstract : Based on the chemotherapeutic literature and cell culture studies of sulfur mustard (SM) toxicity reported here, we believe that DNA repair mechanisms act as cellular defenses against SM toxicity. Cell culture studies show that survival is increased by the nucleotide excision repair mechanism while biochemical studies show that human as well as bacterial glycosylase enzymes can release two SM- induced DNA adducts: 7-hydroxyethylthioethyl guanine and 3-hydroxyethylthioethyl adenine. The growth of cultured human fibroblasts exposed to 10 uM SM appears to be enhanced in comparison with cells incubated continuously at 37 deg C by subjecting them to a period of hypothermia at 28 deg C before returning them to 37 deg C incubation. Cells held at 28 deg C undergo cell cycle arrest and we believe that this arrest may allow more time for DNA repair before the next round of cell division, thus enhancing survival. Concurrently, we have developed a 32P-postlabeling method that can detect one 7-hydroxy-ethylthioethyl guanine in 10(6) DNA nucleotides in DNA extracted from SM-exposed cells. This method should prove useful in both exposure and DNA repair studies.

Descriptors :   *TOXICITY, *DEOXYRIBONUCLEIC ACIDS, *MUSTARD AGENTS, *SULFUR, *CHEMOTHERAPY, HUMANS, BIOCHEMISTRY, ENZYMES, SURVIVAL(GENERAL), REPAIR, DOCUMENTS, DELAY, FIBROBLASTS, CELLS(BIOLOGY), HYPOTHERMIA, CULTURES(BIOLOGY), EXCISION, BACTERIAL TOXINS, NUCLEOTIDES.

Subject Categories : Toxicology
      Pharmacology
      Biochemistry

Distribution Statement : APPROVED FOR PUBLIC RELEASE