Thacker J, Wilkinson R E
DNA Repair and Mutagenesis Group, MRC Radiobiology Unit, Chilton, Didcot, Oxon, England.
Radiat Res. 1995 Dec;144(3):294-300.
Recovery from the lethal effects of irradiation is commonly found when cultured mammalian cells are irradiated at low dose rates when compared to the same cells irradiated at higher dose rates. However, this cellular recovery process is severely reduced or absent in a number of radiosensitive cell lines, including those derived from the human disorder ataxia telangiectasia (AT). The genetic and molecular basis of such recovery processes is not understood, despite their importance. The responses of cells of three further radiosensitive lines, irs1, irs2 and irs3, shown previously to be mutated in different genes, to low-dose-rate radiation are now presented. Plateau-phase cultures of cells of the irs2 line were found to have little or no cellular recovery, while irs1 and irs3 had considerable recovery potential. In comparing the known properties of the radiosensitive lines lacking cellular recovery, including xrs, XR-1 and scid as well as AT and irs2, it is argued that the gene products lacking in these lines normally act coordinately in a specific damage-recognition pathway. The recovery pathway is likely to be associated with the rejoining of DNA double-strand breaks, since several of these recovery-defective lines have a measurable deficiency in break repair.
与以较高剂量率照射的相同细胞相比，当培养的哺乳动物细胞以低剂量率照射时，通常能从辐射的致死效应中恢复。然而，在一些放射敏感细胞系中，包括那些源自人类疾病共济失调毛细血管扩张症（AT）的细胞系，这种细胞恢复过程会严重减少或不存在。尽管这些恢复过程很重要，但其遗传和分子基础仍不清楚。本文现在展示了另外三个先前已证明在不同基因中发生突变的放射敏感细胞系irs1、irs2和irs3的细胞对低剂量率辐射的反应。发现irs2细胞系的平台期培养物几乎没有或没有细胞恢复，而irs1和irs3具有相当大的恢复潜力。在比较缺乏细胞恢复能力的放射敏感细胞系（包括xrs、XR - 1和scid以及AT和irs2）的已知特性时，有人认为这些细胞系中缺乏的基因产物通常在特定的损伤识别途径中协同作用。恢复途径可能与DNA双链断裂的重新连接有关，因为这些恢复缺陷细胞系中有几个在断裂修复方面存在可测量的缺陷。
