Gaziev A I
Radiats Biol Radioecol. 2011 Sep-Oct;51(5):512-29.
This study provides an analysis of the development of cellular response to the critical DNA damage and the mechanisms for limiting the efficiency of repairing such damages induced by low doses of ionizing radiation exposure. Based on the data of many studies, one can conclude that the majority of damages occurring in the DNA of the cells after exposure to ionizing radiation significantly differ in their chemical nature from the endogenous ones. The most important characteristic of radiation-induced DNA damages is their complexity and clustering. Double strand breaks, interstrand crosslinks or destruction of the replication fork and formation of long single-stranded gaps in DNA are considered to be critical damages for the fate of cells. The occurrence of such lesions in DNA may be a key event in the etiology and the therapy of cancer. The appearance in the cells of the critical DNA damage induces a rapid development of a complex and ramified network of molecular and biochemical reactions which are called the cellular response to DNA damage. Induction of the cellular response to DNA damage involves the activation of the systems of cell cycle checkpoints, DNA repair, changes in the expression of many genes, reconstruction of the chromatin or apoptosis. However, the efficiency of repair of the complex DNA damage in cells after exposure to low doses of radiation remains at low levels. The development of the cell response to DNA damages after exposure to low doses of radiation does not reach the desired result due to a small amount of damage, with the progression of the phase cell cycle being ahead of the processes of DNA repair. This is primarily due to the failure of signalization to activate the checkpoint of the cell cycle for its arrest in the case of a small number of critical DNA lesions. In the absence of the arrest of the phase cell cycle progression, especially during the G2/M transition, the reparation mechanisms fail to completely restore DNA, and cells pass into mitosis with a damaged DNA. It is assumed that another reason for the low efficiency of DNA repair in the cells after exposure to low doses of radiation is the existence of a restricted access for the repair system components to the complex damages at the DNA sites of highly compacted chromatin.
本研究分析了细胞对关键DNA损伤的反应发展过程，以及限制低剂量电离辐射暴露诱导的此类损伤修复效率的机制。基于众多研究的数据，可以得出结论：细胞暴露于电离辐射后，DNA中发生的大多数损伤在化学性质上与内源性损伤显著不同。辐射诱导的DNA损伤最重要的特征是其复杂性和聚集性。双链断裂、链间交联或复制叉的破坏以及DNA中长单链缺口的形成被认为是影响细胞命运的关键损伤。DNA中此类损伤的发生可能是癌症病因和治疗中的关键事件。关键DNA损伤在细胞中的出现会引发复杂且分支众多的分子和生化反应网络的快速发展，这些反应被称为细胞对DNA损伤的反应。细胞对DNA损伤反应的诱导涉及细胞周期检查点系统的激活、DNA修复、许多基因表达的变化、染色质的重建或细胞凋亡。然而，低剂量辐射暴露后细胞中复杂DNA损伤的修复效率仍然很低。低剂量辐射暴露后细胞对DNA损伤的反应发展未达到预期结果，这是因为损伤数量少，细胞周期阶段的进展领先于DNA修复过程。这主要是由于在少量关键DNA损伤情况下，信号传导未能激活细胞周期检查点使其停滞。在细胞周期阶段进展未停滞的情况下，尤其是在G2/M转换期间，修复机制无法完全恢复DNA，细胞带着受损的DNA进入有丝分裂。据推测，低剂量辐射暴露后细胞中DNA修复效率低的另一个原因是修复系统组件难以接触到高度致密染色质DNA位点处的复杂损伤。
