Mathieu J, Ferlat S, Ballester B, Platel S, Herodin F, Chancerelle Y, Mestries J C, Kergonou J F
Centre de Recherches du Service de Santé des Armées, La Tronche, France.
Radiat Res. 1996 Dec;146(6):652-9.
Apoptosis is a process of physiological cell death characterized by DNA fragmentation, chromatin condensation, loss of membrane asymmetry, mitochondrial alterations and cell lethality. In the present study, apoptosis induced in thymocytes by gamma irradiation is evaluated by flow cytometry, by a diphenylamine colorimetric method and by gel electrophoresis. Treatment of thymocytes with diethyldithiocarbamate or zinc shows that these compounds can inhibit radiation-induced apoptosis. Moreover, a synergistic effect is observed by using combinations of both compounds: ZnSO4 potentiates the effect of diethyldithiocarbamate at concentrations at which the compounds used separately show a low efficacy. A study of kinetics shows that addition of 1 microM diethyldithiocarbamate + 50 microM ZnSO4 (the most efficient combination) after irradiation can decrease DNA fragmentation even when it is added 2-3 h after irradiation. However, 1 microM diethyldithiocarbamate + 50 microM ZnSO4 cannot prevent the radiation-induced loss of membrane asymmetry and the decrease in alteration of the mitochondrial membrane as measured by binding of merocyanine 540 and uptake of rhodamine 123, respectively.
细胞凋亡是一种生理性细胞死亡过程，其特征为DNA片段化、染色质浓缩、膜不对称性丧失、线粒体改变及细胞死亡。在本研究中，通过流式细胞术、二苯胺比色法和凝胶电泳对γ射线照射诱导的胸腺细胞凋亡进行评估。用二乙基二硫代氨基甲酸盐或锌处理胸腺细胞表明，这些化合物可抑制辐射诱导的细胞凋亡。此外，使用两种化合物的组合可观察到协同效应：在单独使用时效果较低的浓度下，硫酸锌可增强二乙基二硫代氨基甲酸盐的作用。动力学研究表明，照射后添加1微摩尔二乙基二硫代氨基甲酸盐 + 50微摩尔硫酸锌（最有效的组合）即使在照射后2 - 3小时添加也可减少DNA片段化。然而，1微摩尔二乙基二硫代氨基甲酸盐 + 50微摩尔硫酸锌不能阻止辐射诱导的膜不对称性丧失以及分别通过部花青540结合和罗丹明123摄取所测量的线粒体膜改变的减少。
