2,2'-Dichlorodiethyl sulfide (sulfur mustard) decreases NAD+ levels in human leukocytes.
2,2'-Dichlorodiethyl sulfide (sulfur mustard, HD) extensively alkylates DNA in a concentration-dependent manner in many cell types. We have proposed a biochemical hypothesis that explains HD-induced 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.
Meier
H L
HL
Biochemical Pharmacology, USAMRICD, Aberdeen Proving Ground, MD 21010.
Gross
C L
CL
Papirmeister
B
B
D006098:Granulocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism*; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D009150:Mustard Compounds / Q000633:toxicity*; D009151:Mustard Gas / Q000633:toxicity*; D009243:NAD / Q000097:blood* / Q000302:isolation & purification; D010084:Oxidation-Reduction
D009150:Mustard Compounds; D009243:NAD; D009151:Mustard Gas