HAS CELLULAR REPAIR (PLD, SLD, ETC.) COMMON MOLECULAR BA

已经设计了实验来检验这两个细胞 哺乳动物细胞暴露在稀疏环境中后的修复活动 电离辐射(从亚致死损伤(SLD)中恢复 分剂量实验和潜在致命损伤(PLD)的修复 在细胞的各种辐射后处理后观察到的)可能具有 常见的一类分子损伤，其修复和/或固定 导致在细胞水平上观察到的影响，即使在不同的 实验性协议。此外，还将检验这一假设 在整个细胞周期中观察到的细胞存活的变化可能是 分子介导的PLD修复和/或固定效果 在细胞周期的某些边界启动的活动。要测试 第一个假设，实验将在平台期V79和 10个T1/2细胞对β-araA和β-araA诱导的PLD表达的影响 β-Arac，DNA聚合酶Alpha和Beta的特异性抑制剂。在……里面 其他细胞系统，这些处理主要影响肩宽(DQ) 生存曲线的一部分。亚致死状态恢复的修复动力学 PLD的损伤和修复，通过用不同的抑制剂治疗来衡量 照射后的时间，将进行比较。更进一步，波谱 受这些治疗影响的潜在致命损害将与 放射治疗后受影响的潜在致命性皮损 以高渗溶液为判据(A)修复时间常数 观察到，以及(B)每种处理对参数的影响 生存曲线。也通过筛选对PLD修复的影响 DNA聚合酶α的特定抑制剂，如APHIDICOIN， 聚合酶Alpha或Beta将参与这些修复过程 测试过。 为了检验第二个假设，咖啡因在表达 潜在的致命损害将在整个细胞周期中进行研究，并 给药浓度和给药时间下的存活曲线 最大效果将与在边界获得的效果进行比较 最高灵敏度。单相性PLD的可修复性 细胞周期也将在随后的阶段通过孵化细胞来测试 在适当的条件下，因为它们在循环中进行测试 G1/S交界期和有丝分裂期是否是未修复阶段， 潜在的致命伤害就会被修复。

Experiments have been designed to test the hypothesis that the two cellular repair activities observed after exposure of mammalian cells to sparsely ionizing radiations (recovery from sublethal damage (SLD) as observed in split-dose experiments, and repair of potentially lethal damage (PLD) observed after various postirradiation treatments of cells) might have a class of molecular lesions in common, the repair and/or fixation of which causes the effects observed at the cellular level, even in different experimental protocols. Also, the hypothesis will be tested that the variation in cell survival, observed throughout the cell cycle, might be the result of repair and/or fixation of PLD mediated by molecular activities initiated at certain borders of the cell cycle. To test the first hypothesis, experiments will be performed with plateau phase V79 and 10 T 1/2-cells on the expresion of PLD as caused by Beta-araA and Beta-araC, specific inhibitors of the DNA polymerases Alpha and Beta. In other cell systems, these treatments mainly affect the shoulder width (Dq) of the survival curve. The repair kinetics for recovery from sublethal damage and repair of PLD, as measured by treatment with inhibitors various times after irradiation, will be compared. Further, the spectrum of potentially lethal lesions affected by these treatments will be compared to that of potentially lethal lesions affected after postirradiation treatment with hypertonic solutions using as criteria (a) the repair time constants observed, and (b) the effect of each treatment on the parameters of the survival curve. By screening also the effects on the repair of PLD of specific inhibitors of DNA polymerase Alpha, such as aphidicolin, the involvement of polymerase Alpha or Beta in these repair processes will be tested. To test the second hypothesis, the effects of caffeine in expressing potentially lethal damage will be studied throughout the cell cycle, and the survival curves obtained at concentrations and treatment times giving maximal effect will be compared with those obtained at the borders of maximal sensitivity. The reparability of PLD induced in one phase of the cell cycle will also be tested in subsequent phases by incubating cells under appropriate conditions as they progress through the cycle to test whether G1/S-border and mitosis are the stages in which unrepaired, potentially lethal damage becomes fixed.