Smith W J, Gross C L, Chan P, Meier H L
Biochemical Pharmacology Branch, U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland 21010-5425.
Cell Biol Toxicol. 1990 Jul;6(3):285-91. doi: 10.1007/BF02443803.
Human epidermal keratinocytes in culture were studied to evaluate their usefulness in demonstrating toxic events following exposure to sulfur mustard. Exposure of keratinocytes to sulfur mustard over a concentration range of 1-1000 microM HD, reduced NAD + levels from 96% to 32% of control levels. When keratinocytes were exposed to a concentration of 300 microM HD, NAD + levels began to fall at 1 hour and reached a plateau of 47% of control levels at 4 hours. Niacinamide, an inhibitor of the enzyme poly(ADP-ribose) polymerase, partially protected mustard-exposed cells against NAD + depletion. It also protected cellular viability as assessed by vital staining 24 hours after exposure. This protection was not seen in long-term (72 hr) cultures. These studies suggest that human epidermal keratinocytes in culture can serve as a useful in vitro model for research into the biochemical mechanisms of sulfur mustard-induced cutaneous injury.
对培养中的人表皮角质形成细胞进行了研究，以评估其在显示接触硫芥后毒性事件方面的效用。将角质形成细胞暴露于浓度范围为1-1000微摩尔/升硫芥（HD）中，会使烟酰胺腺嘌呤二核苷酸（NAD+）水平从对照水平的96%降至32%。当角质形成细胞暴露于300微摩尔/升HD浓度时，NAD+水平在1小时开始下降，并在4小时达到对照水平47%的平台期。烟酰胺，一种聚（ADP-核糖）聚合酶的抑制剂，部分保护了硫芥暴露的细胞免受NAD+耗竭。通过暴露24小时后的活体染色评估，它还保护了细胞活力。在长期（72小时）培养中未观察到这种保护作用。这些研究表明，培养中的人表皮角质形成细胞可作为研究硫芥诱导皮肤损伤生化机制的有用体外模型。
