Accession Number : ADP008772
Title : Cytometric Analysis of DNA Changes Induced by Sulfur Mustard
Corporate Author : ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD
Personal Author(s) : Smith, W. J. ; Sanders, K. M. ; Ruddle, S. E. ; Gross, C. L.
Report Date : 13 MAY 1993
Pagination or Media Count : 11
Abstract : Sulfur mustard is an alkylating agent which causes severe, potentially debilitating blisters following cutaneous exposure. Its mechanism of pathogenesis is unknown and no antidote exists to prevent its pathology. The biochemical basis of sulfur mustard's vesicating activity has been hypothesized to be a cascade of events beginning with alkylation of DNA. Using human cells in culture, we have assessed the effects of sulfur mustard on cell cycle activity using flow cytometry with propidium iodide. Two distinct patterns emerged, a Gl/ S interface block at concentrations equivalent to vesicating doses (>50-micronM) and a G2 block at 10-fold lower concentrations. In addition, noticeable increases in amount of dye uptake were observed at 4 and 24 hours after sulfur mustard exposure. These increases are believed to be related to DNA repair activities and can be prevented by treatment of the cells with niacinamide, which inhibits DNA repair. Other drugs which provide alternate alkylating sites or inhibit cell cycle progression were shown to lower the cytotoxicity of sulfur mustard and to protect against its direct DNA damaging effects.
Descriptors : *DEOXYRIBONUCLEIC ACIDS , *MUSTARD AGENTS , *IMMUNOCHEMISTRY , HUMANS , INTERFACES , CELLS , TOXICITY , SITES , CYCLES , REPAIR , PATTERNS , ANTIDOTES , ALKYLATION , FLOW , DYES , CYTOTOXINS , PATHOLOGY , SULFUR , DRUGS , CULTURE , PATHOGENESIS , HD AGENT , IODIDES , ADDITION.
Subject Categories : BIOCHEMISRTY
CHEMICAL, BIOLOGICAL AND RADIOLOGICAL WARFARE
Distribution Statement : APPROVED FOR PUBLIC RELEASE