Radiosensitization of hypoxic mammalian cells by diamide. II. Studies of mechanism.
Radiosensitization of hypoxic mammalian cells by diamide. II. Studies of mechanism.
复制标题
二酰胺对缺氧哺乳动物细胞的放射增敏作用。
作者：
J. Harris;C. Koch;J. Power;J. Biaglow
二胺（二氮二羧酸双（N，N'-二甲酰胺））通过降低生存曲线肩线（低浓度）和增加斜率（高浓度）使缺氧的中国仓鼠细胞放射致敏。我们通过在不同温度和底物可用性条件下照射细胞并测量其存活或DNA损伤（染色体畸变和链断裂）来研究这两种现象的机制。结果证实，不同的机制负责这两种影响。对肩部的影响似乎是由于内源性非蛋白巯基和减少的吡啶核苷酸的氧化，这些化合物通常会对某些（单击型）损伤产生快速化学修复作用。另一方面，斜率效应可能是由于与DNA的反应类似于对电子亲和化合物的反应。这些结果，连同缺氧细胞在低温下辐照去除二胺后仍保持敏化的发现，为化学放射敏化问题提供了一个有用的模型和新的实验方法。
Diamide (diazenedicarboxylic acid bis(N,N'-dimethylamide)) radiosensitizes hypoxic Chinese hamster cells by decreasing the shoulder of the survival curve (at low concentrations) and increasing the slope (at high concentrations). We studied the mechanisms responsible for these two phenomena by irradiating cells under different conditions of temperature and substrate availability and measuring either their survival or DNA damage (chromosome aberrations and strand breaks). The results confirm that different mechanisms are responsible for the two effects. The effect on the shoulder appeared to be due to oxidation of endogenous nonprotein sulfhydryls and reduced pyridine nucleotides, compounds that would normally effect rapid chemical repair of certain (single-hit type) lesions. The slope effect, on the other hand, may have been due to reactions with DNA similar to those that have been described for the electron-affinic compounds. These results, together with the finding that hypoxic cells remained sensitized after the removal of diamide when they were irradiated in the cold, provide a useful model and a new experimental approach to the question of chemical radiosensitization.