Dipartimento di Fisica, Università degli studi di Pavia, Pavia, Italy ; Istituto Nazionale di Fisica Nucleare, Sezione di Pavia, Pavia, Italy.
PLoS One. 2013 Nov 29;8(11):e79541. doi: 10.1371/journal.pone.0079541. eCollection 2013.
Radiation therapy is one of the most common and effective strategies used to treat cancer. The irradiation is usually performed with a fractionated scheme, where the dose required to kill tumour cells is given in several sessions, spaced by specific time intervals, to allow healthy tissue recovery. In this work, we examined the DNA repair dynamics of cells exposed to radiation delivered in fractions, by assessing the response of histone-2AX (H2AX) phosphorylation (γ-H2AX), a marker of DNA double strand breaks. γ-H2AX foci induction and disappearance were monitored following split dose irradiation experiments in which time interval between exposure and dose were varied. Experimental data have been coupled to an analytical theoretical model, in order to quantify key parameters involved in the foci induction process. Induction of γ-H2AX foci was found to be affected by the initial radiation exposure with a smaller number of foci induced by subsequent exposures. This was compared to chromatin relaxation and cell survival. The time needed for full recovery of γ-H2AX foci induction was quantified (12 hours) and the 1:1 relationship between radiation induced DNA double strand breaks and foci numbers was critically assessed in the multiple irradiation scenarios.
放射治疗是治疗癌症最常用和最有效的策略之一。照射通常采用分次方案进行，其中分次给予杀死肿瘤细胞所需的剂量，间隔特定的时间间隔，以允许健康组织恢复。在这项工作中，我们通过评估组蛋白-2AX（H2AX）磷酸化（γ-H2AX）的反应来检查细胞在分次照射下的 DNA 修复动力学，γ-H2AX 焦点的诱导和消失在暴露和剂量之间的时间间隔变化的分割剂量照射实验中进行了监测。将实验数据与分析理论模型相结合，以量化焦点诱导过程中涉及的关键参数。诱导γ-H2AX 焦点的数量受到初始辐射暴露的影响，后续暴露诱导的焦点数量较少。这与染色质松弛和细胞存活进行了比较。定量了完全恢复γ-H2AX 焦点诱导所需的时间（12 小时），并在多次照射情况下对辐射诱导的 DNA 双链断裂与焦点数量之间的 1:1 关系进行了严格评估。
