Sulfur mustard lowers nicotinamide adenine dinucleotide concentrations in human skin grafted to athymic nude mice.
Human skin grafted to athymic nude mice shows a decrease in nicotinamide adenine dinucleotide (NAD+) concentrations when exposed to sulfur mustard (HD). The lowering of NAD+ is dependent on both dose of HD and time after exposure. When HD is applied to grafted skin at 127 micrograms/cm2, the decrease in NAD+ begins immediately after exposure, approaches minimal values by 4 hr. NAD+ returned to normal within 18 hr. With higher concentrations of HD, NAD+ concentrations fall precipitously within 4 hr, reach a minimum value at 18 hr, and seem to remain at this depressed value for at least 72 hr. NAD+ loss appears to precede and be proportional to tissue injury. Pretreatment of mice with 3-aminobenzamide, a specific inhibitor of poly(ADP-ribose) polymerase, seems to lessen the effect of HD. At higher concentrations of HD, human grafts from mice pretreated with 3-aminobenzamide show significant protection from loss of NAD+ levels after 4 hr.
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D001706:Biopsy; D004305:Dose-Response Relationship, Drug; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009150:Mustard Compounds / Q000633:toxicity*; D009151:Mustard Gas / Q000633:toxicity*; D009243:NAD / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051381:Rats; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D016038:Skin Transplantation; D014183:Transplantation, Heterologous
D001549:Benzamides; D009150:Mustard Compounds; D009243:NAD; C025160:3-aminobenzamide; D011065:Poly(ADP-ribose) Polymerases; D009151:Mustard Gas