Qi J P, Shao S H, Xie Jinli, Zhu Y
College of Information Sciences & Technology, Donghua University, Shanghai 201620, China.
Biosystems. 2007 Nov-Dec;90(3):698-706. doi: 10.1016/j.biosystems.2007.02.007. Epub 2007 Mar 6.
P53, a vital anticancer gene, controls the transcription and translation of a series of genes, and implement the cell cycle arrest and cell apoptosis by regulating their complicated signal pathways. Under radiotherapy, cell can trigger internal self-defense mechanisms in fighting against genome stresses induced by acute ion radiation (IR). To simulate the investigating of cellular responding acute IR at single cell level further, we propose a model of P53 gene regulatory networks under radiotherapy. Our model can successfully implement the kinetics of double strand breaks (DSBs) generating and their repair, ataxia telangiectasia mutated (ATM) activation, as well as P53-MDM2 feedback regulating. By comparing simulations under different IR dose, we can try to find the optimal strategy in controlling of IR dose and therapy time, and provide some theoretical analysis to obtain much better outcome of radiotherapy further.
P53是一种重要的抗癌基因，它控制一系列基因的转录和翻译，并通过调节其复杂的信号通路来实现细胞周期阻滞和细胞凋亡。在放疗过程中，细胞会触发内部自我防御机制以对抗急性电离辐射（IR）诱导的基因组应激。为了进一步模拟在单细胞水平上对细胞对急性IR反应的研究，我们提出了一种放疗条件下P53基因调控网络模型。我们的模型能够成功实现双链断裂（DSB）的产生及其修复动力学、共济失调毛细血管扩张症突变基因（ATM）的激活以及P53-MDM2反馈调节。通过比较不同IR剂量下的模拟结果，我们试图找到控制IR剂量和治疗时间的最佳策略，并进一步提供一些理论分析以获得更好的放疗效果。
