The time-dependent effect of 2,2'-dichlorodiethyl sulfide (sulfur mustard, HD, 1,1'-thiobis [2-chloroethane]) on the lymphocyte viability and the kinetics of protection by poly(ADP-ribose) polymerase inhibitors.
2,2'-Dichlorodiethyl sulfide (sulfur mustard, HD, 1,1'-thiobis [2-chloroethane]) is a potent vesicant which can cause severe lesions to skin, lung, and eyes. Due to the high number of debilitating exposures during the Iran-Iraq war to the alkylating agent, HD, there is an increased interest in its mechanism of action and in the development of therapeutic interventions to prevent HD-induced lesions. Recently we reported an in vitro assay using human mononuclear leukocytes for studying HD-induced pathology. To study the time dependence of HD-induced mononuclear leukocyte cell death and to determine the parameters of any potential therapeutic intervention, an assay was developed and automated using a flow cytometer to measure propidium iodide exclusion by mononuclear cells. This assay demonstrated that HD-initiated cell death did not begin before 4 h post-exposure, but after 4 h proceeded in a concentration-dependent manner. In this assay, both niacinamide and 3-aminobenzamide, poly(ADP-ribose) polymerase inhibitors, were shown to be effective in blocking HD-induced cell death when added to the cultures during the first 4 h post-exposure. They offered partial protection when added between 6 and 12 h and were of no benefit when added after 12 h post-exposure.
Meier
H L
HL
United States Army Medical Research Institute of Chemical Defense, Maryland, USA.
D000478:Alkylation; D002470:Cell Survival / Q000187:drug effects; D002619:Chemical Warfare Agents / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008214:Lymphocytes / Q000187:drug effects*; D009151:Mustard Gas / Q000494:pharmacology*; D009525:Niacin / Q000494:pharmacology; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D013997:Time Factors
D002619:Chemical Warfare Agents; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D009525:Niacin; D004247:DNA; D009151:Mustard Gas