Iliakis G, Pantelias G E, Seaner R
Thomas Jefferson University Hospital, Department of Radiation Therapy and Nuclear Medicine, Philadelphia, Pennsylvania 19107.
Radiat Res. 1988 May;114(2):361-78.
The effect of the DNA polymerase inhibitor beta-arabinofuranosyladenine (araA) on radiation-induced damage was studied at the cell survival and chromosome level in unfed plateau-phase cultures of Chinese hamster ovary cells. At the cell survival level postirradiation treatment with araA fixed a form of radiation-induced potentially lethal damage, termed alpha-PLD. In the absence of araA treatment, repair of PLD resulted in the formation of the survival curve shoulder in immediately plated cells and in the increase in survival observed after delayed plating. The repair kinetics observed after delayed plating of plateau-phase cells or after delayed administration of 500 microM araA were similar, suggesting that both protocols assay similar lesions. AraA-mediated fixation reached a plateau at concentrations higher than 500 microM, indicating complete fixation of alpha-PLD. At the cytogenetic level, postirradiation treatment with araA at concentrations higher than 500 microM caused a complete inhibition of chromosome repair, as scored by premature chromosome condensation. In the absence of araA, the linearity of the dose-effect relationship for chromosome fragmentation obtained immediately after irradiation was preserved even after long repair times. The repair kinetics of chromosome damage measured in cells held postirradiation in the plateau phase were the mirror image of the repair kinetics for alpha-PLD. The half-time was 1 h in both cases and repair reached a plateau after about 4-6 h. AraA-mediated repair inhibition of chromosome damage was reversible, and a decrease in residual chromosome damage was observed after post-treatment incubation in araA-free conditioned medium. This persistent chromosome damage increased with increasing araA concentration and, as with PLD fixation, reached a plateau at about 500 microM. These results suggest that repair and araA-mediated fixation of alpha-PLD have their counterparts at the chromosome level as indicated by the similar repair kinetics and inhibition/fixation characteristics obtained for alpha-PLD and chromosome damage. This relationship implies a correlation between repair at the DNA and the chromosome level and suggests that DNA polymerization is required for the repair of chromosome damage.
在中国仓鼠卵巢细胞未喂食的平台期培养物中，在细胞存活和染色体水平上研究了DNA聚合酶抑制剂β-阿拉伯呋喃糖腺嘌呤（araA）对辐射诱导损伤的影响。在细胞存活水平上，照射后用araA处理固定了一种辐射诱导的潜在致死损伤形式，称为α-PLD。在没有araA处理的情况下，PLD的修复导致立即接种的细胞中存活曲线肩部的形成以及延迟接种后观察到的存活率增加。在平台期细胞延迟接种或延迟给予500μM araA后观察到的修复动力学相似，表明两种方案检测的是相似的损伤。araA介导的固定在高于500μM的浓度时达到平台期，表明α-PLD完全固定。在细胞遗传学水平上，高于500μM浓度的araA照射后处理导致染色体修复完全抑制，通过早熟染色体凝缩评分。在没有araA的情况下，即使在长时间修复后，照射后立即获得的染色体断裂剂量效应关系的线性仍然保持。在平台期照射后保持的细胞中测量的染色体损伤修复动力学是α-PLD修复动力学的镜像。两种情况下的半衰期均为1小时，修复在约4-6小时后达到平台期。araA介导的染色体损伤修复抑制是可逆的，在无araA的条件培养基中处理后孵育后观察到残留染色体损伤减少。这种持续的染色体损伤随着araA浓度的增加而增加，并且与PLD固定一样，在约500μM时达到平台期。这些结果表明，α-PLD的修复和araA介导的固定在染色体水平上有其对应物，这由α-PLD和染色体损伤获得的相似修复动力学和抑制/固定特征表明。这种关系意味着DNA和染色体水平的修复之间存在相关性，并表明DNA聚合是染色体损伤修复所必需的。
