Meier H L, Gross C L, Papirmeister B
Biochemical Pharmacology, USAMRICD, Aberdeen Proving Ground, MD 21010.
Toxicol Lett. 1987 Nov;39(1):109-22. doi: 10.1016/0378-4274(87)90263-3.
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.
2,2'-二氯二乙硫醚（硫芥，HD）在许多细胞类型中以浓度依赖的方式广泛地使DNA烷基化。我们提出了一个生化假说，该假说通过将DNA烷基化和DNA断裂与聚（ADP - 核糖）聚合酶的激活联系起来，解释HD诱导的损伤，从而导致细胞内NAD+耗竭。通过用HD处理人类白细胞来测试这个假说，以确定NAD+耗竭是否如预期那样发生。这些细胞显示出NAD+水平下降，这取决于HD的浓度和暴露后的时间。聚（ADP - 核糖）聚合酶抑制剂或NAD+合成底物能够防止HD诱导的NAD+下降。
