Iliakis G, Pantelias G, Kurtzman S
Thomas Jefferson University Hospital, Department of Radiation Oncology and Nuclear Medicine, Philadelphia, Pennsylvania 19107.
Radiat Res. 1991 Jan;125(1):56-64.
The effect of BrdU incorporation on cell radiosensitivity as well as on the induction of chromosome damage by radiation was studied in plateau-phase xrs-5 cells using the premature chromosome condensation (PCC) method. It is well known that xrs-5 cells are sensitive to ionizing radiation and defective in the repair of radiation-induced DNA double-strand breaks, chromosome damage, and potentially lethal damage (PLD). Compared to repair-proficient CHO 10B cells, a reduction was observed in the overall BrdU-mediated radiosensitization in plateau-phase xrs-5 cells for the same degree of thymidine replacement. This finding is interpreted with a model for BrdU-induced radiosensitization advanced previously, in which two distinct components act to produce the overall radiosensitization observed. One component involves processes associated with the increase in initial damage (DNA and chromosome) production per unit absorbed dose and causes an increase in the slope of the survival curve, while the second component involves enhanced fixation of radiation-induced damage (PLD) and causes a reduction in the width of the shoulder of the survival curve. It is suggested that in plateau-phase xrs-5 cells, the deficiency in the repair of radiation-induced damage compromises BrdU-mediated radiosensitization by leaving active only the radiosensitization component that is associated with an increase in damage induction. Enhancement of cell killing by BrdU in plateau-phase xrs-5 cells resulted in a decrease in D0, the relative value of which was similar to the relative increase in the production of chromosome damage as measured by the PCC method. The relative values for the change in D0 and the production of chromosome aberrations were similar in plateau-phase CHO 10B and xrs-5 cells, suggesting that the physicochemical and/or biochemical processes associated with this phenomenon are the same in the two cell lines. Radiosensitization of a magnitude similar to that observed in exponentially growing CHO 10B cells was induced by BrdU in exponentially growing xrs-5 cells. This effect is attributed to a partial expression of the repair gene (transiently during S phase in all cells, or throughout the cycle in a fraction of cells) that permits some repair of radiation-induced damage and which is compromised by BrdU.
利用早熟染色体凝聚（PCC）方法，在平台期xrs - 5细胞中研究了BrdU掺入对细胞辐射敏感性以及辐射诱导染色体损伤的影响。众所周知，xrs - 5细胞对电离辐射敏感，在修复辐射诱导的DNA双链断裂、染色体损伤和潜在致死损伤（PLD）方面存在缺陷。与修复能力正常的CHO 10B细胞相比，在相同程度的胸苷替代情况下，观察到平台期xrs - 5细胞中BrdU介导的总体辐射增敏作用有所降低。这一发现用先前提出的BrdU诱导辐射增敏的模型来解释，在该模型中，两个不同的成分共同作用产生观察到的总体辐射增敏作用。一个成分涉及与每单位吸收剂量初始损伤（DNA和染色体）产生增加相关的过程，并导致存活曲线斜率增加，而第二个成分涉及辐射诱导损伤（PLD）的增强固定，并导致存活曲线肩部宽度减小。有人认为，在平台期xrs - 5细胞中，辐射诱导损伤修复的缺陷通过仅使与损伤诱导增加相关的辐射增敏成分保持活性，从而损害了BrdU介导的辐射增敏作用。BrdU对平台期xrs - 5细胞杀伤作用的增强导致D0降低，其相对值与通过PCC方法测量的染色体损伤产生的相对增加相似。平台期CHO 10B细胞和xrs - 5细胞中D0变化和染色体畸变产生的相对值相似，表明与该现象相关的物理化学和/或生物化学过程在这两种细胞系中是相同的。BrdU在指数生长的xrs - 5细胞中诱导出与在指数生长的CHO 10B细胞中观察到的类似程度的辐射增敏作用。这种效应归因于修复基因的部分表达（在所有细胞的S期短暂表达，或在一部分细胞的整个周期中表达），该表达允许对辐射诱导的损伤进行一些修复，而BrdU会损害这种修复。
