2,2'-Dichlorodiethyl sulfide (sulfur mustard) decreases NAD+ levels in human leukocytes.

Abstract 2,2′-Dichlorodiethyl sulfide (sulfur mustard, HD) extensively alkylates DNA in a concentrationdependent manner in many cell types. We have proposed a biochemical hypothesis that explains HDinduced injury by linking DNA alkylation and DNA breaks with activation of poly(ADP-ribose) polymerase, resulting in depletion of cellular NAD + . This hypothesis was tested by treating human leukocytes with HD to determine whether NAD + depletion occurred as predicted. These cells demonstrated a decrease in NAD + levels which was dependent on both concentration of HD and time after exposure. Inhibitors of poly(ADP-ribose) polymerase or substrates for NAD + synthesis were able to prevent the HD-induced NAD + decrease.