CYTOMETRIC ANALYSIS OF DNA CHANGES INDUCED BY SULFUR MUSTARD

Sulfur mustard is an alkylating agent that causes severe, potentially debilitating blisters following cutaneous exposure. Its mechanism of p athogenesis is unknown and no antidote exists. The biochemical basis o f sulfur mustard's vesicating activity has been hypothesized to be a c ascade of events beginning with alkylation of DNA. Using human cells i n culture, we h assessed the effects of sulfur mustard on cell cycle a ctivity using flow cytometry with propidium iodide. Two distinct patte rns emerged: a G1/S interface block at concentrations equivalent to ve sicating doses (>50 mu M) and a G2 block at 10-fold lower concentratio ns. In addition, noticeable increases in amount of dye uptake were obs erved at 4 and 24 hr after sulfur mustard exposure. These increases ar e 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 that provide alternative alkylating sites or inhibit cel l cycle progression were shown to lower the cytotoxicity of sulfur mus tard and to protect against its direct DNA-damaging effects.