Kimler B F
Int J Radiat Oncol Biol Phys. 1982 Aug;8(8):1333-8. doi: 10.1016/0360-3016(82)90583-1.
Razoxane [(+/-)-1,2-bis(3,5-dioxopiperazine-1-yl)propane] was investigated for its effects on the survival of irradiated Chinese hamster fibroblasts in vitro. Razoxane alone produced cytotoxicity that was dependent upon drug concentration and pulse exposure time, with a preferential lethality for cells treated while in the DNA-synthetic phase. Razoxane enhanced radiation-induced cell killing when used as either a pulse exposure or a continuous treatment. In asynchronous populations of cells, this was expressed as an increase in the slope and a reduction in the shoulder of the radiation dose-survival curve. In synchronous populations of cells, a modest increase in cell killing was observed for those cells treated in G1 and G2, with a greater enhancement for cells treated in the S-phase. Overall, razoxane may potentiate the radiation-induced killing of cultured mammalian cells by a number of mechanisms: 1) a blockade of cell cycle progression causing an accumulation of cells in radiosensitive phases of the cell cycle; 2) selective cytotoxicity of cells in radioresistant phases of the cell cycle; 3) inhibition of the accumulation of sublethal radiation damage; or 4) interaction of the damages induced by each agent so as to produce an enhanced effect. These mechanisms may need to be considered if razoxane and radiation therapy are to be used in combined modality therapeutic approaches.
丙亚胺[（±）-1,2-双（3,5-二氧代哌嗪-1-基）丙烷]对体外照射的中国仓鼠成纤维细胞的存活影响进行了研究。单独使用丙亚胺产生的细胞毒性取决于药物浓度和脉冲暴露时间，对处于DNA合成期的细胞具有优先致死性。当丙亚胺用作脉冲暴露或连续处理时，可增强辐射诱导的细胞杀伤作用。在异步细胞群体中，这表现为辐射剂量-存活曲线的斜率增加和肩部降低。在同步细胞群体中，观察到在G1期和G2期处理的细胞杀伤作用适度增加，而在S期处理的细胞增强作用更大。总体而言，丙亚胺可能通过多种机制增强辐射诱导的培养哺乳动物细胞杀伤作用：1）细胞周期进程的阻断导致细胞在细胞周期的放射敏感阶段积累；2）细胞周期放射抗性阶段细胞的选择性细胞毒性；3）抑制亚致死性辐射损伤的积累；或4）每种药物诱导的损伤相互作用以产生增强效应。如果丙亚胺和放射治疗要用于联合治疗方法，则可能需要考虑这些机制。
