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

Title2,2'-Dichlorodiethyl sulfide (sulfur mustard) decreases NAD+ levels in human leukocytes
Publication TypeJournal Article
Year of Publication1987
AuthorsMeier H.L, Gross C.L, Papirmeister B.
JournalToxicol LettToxicol Lett
Volume39
Pagination109-122
Date PublishedNov
ISBN Number0378-4274 (Print)
Accession Number3672551
KeywordsGranulocytes/drug effects/metabolism, Humans, Kinetics, Leukocytes/drug effects/*metabolism, Lymphocytes/drug effects/metabolism, Mustard Compounds/*toxicity, Mustard Gas/*toxicity, NAD/*blood/isolation & purification, Oxidation-Reduction
Abstract

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.

Short TitleToxicology letters

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