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使用 Geant4-DNA 修复 HSGc-C5 癌细胞的性能评估
发表日期:2022-01-12

Performance Evaluation for Repair of HSGc-C5 Carcinoma Cell Using Geant4-DNA

使用 Geant4-DNA 修复 HSGc-C5 癌细胞的性能评估


To evaluate the repair performance of HSGc-C5 carcinoma cell against radiation-induced DNA damage, a Geant4-DNA application for radiobiological research was extended by using newly measured experimental data acquired in this study. Concerning fast- and slow-DNA rejoining, the two-lesion kinetics (TLK) model parameters were adequately optimized (the repair speeds of each process were reasonably close to the DNA rejoining speed of the nonhomologous end-joining and homologous recombination pathways). The lethality probabilities of the DNA damage induced by complex double strand breaks (DSBs) and binary repair were approximately 3% and 40%, respectively. Using the optimized repair parameters, the Geant4-DNA simulation was able to predict the cell surviving fraction (SF) and the DNA repair kinetics.

为了评估 HSGc-C5 癌细胞对辐射诱导的 DNA 损伤的修复性能,通过使用本研究中获得的新测量的实验数据,扩展了 Geant4-DNA 在放射生物学研究中的应用。在快速和慢速 DNA 重新连接方面,双损伤动力学 (TLK) 模型参数得到了充分优化(每个过程的修复速度合理地接近非同源末端连接和同源重组途径的 DNA 重新连接速度)。复杂双链断裂 (DSB) 和二元修复诱导的 DNA 损伤的致死概率约为3 % 40 %, 分别。使用优化的修复参数,Geant4-DNA 模拟能够预测细胞存活分数 (SF) DNA 修复动力学。

10层细胞工厂

10层细胞工厂

Track-structure Monte Carlo simulations are useful tools to evaluate initial DNA damage induced by irradiation. In the previous study, we have developed a Gean4-DNA-based application to estimate the cell surviving fraction of V79 cells after irradiation, bridging the gap between the initial DNA damage and the DNA rejoining kinetics by means of the two-lesion kinetics (TLK) model. However, since the DNA repair performance depends on cell line, the same model parameters cannot be used for different cell lines. Thus, we extended the Geant4-DNA application with a TLK model for the evaluation of DNA damage repair performance in HSGc-C5 carcinoma cells which are typically used for evaluating proton/carbon radiation treatment effects. For this evaluation, we also performed experimental measurements for cell surviving fractions and DNA rejoining kinetics of the HSGc-C5 cells irradiated by 70 MeV protons at the cyclotron facility at the National Institutes for Quantum and Radiological Science and Technology (QST). Concerning fast- and slow-DNA rejoining, the TLK model parameters were adequately optimized with the simulated initial DNA damage. The optimized DNA rejoining speeds were reasonably agreed with the experimental DNA rejoining speeds. Using the optimized TLK model, the Geant4-DNA simulation is now able to predict cell survival and DNA-rejoining kinetics for HSGc-C5 cells. View Full-Text

高效摇瓶

高效摇瓶

轨道结构蒙特卡罗模拟是评估辐射引起的初始 DNA 损伤的有用工具。在之前的研究中,我们开发了一种基于 Gean4-DNA 的应用程序来估计辐照后 V79 细胞的细胞存活率,通过双损伤动力学(TLK)弥合初始 DNA 损伤和 DNA 重新连接动力学之间的差距) 模型。然而,由于 DNA 修复性能取决于细胞系,相同的模型参数不能用于不同的细胞系。因此,我们使用 TLK 模型扩展了 Geant4-DNA 应用,用于评估 HSGc-C5 癌细胞中的 DNA 损伤修复性能,这些细胞通常用于评估质子/碳辐射治疗效果。对于本次评测,我们还在美国国家量子与放射科学与技术研究所 (QST) 的回旋加速器设施中对 70 MeV 质子照射的 HSGc-C5 细胞的细胞存活部分和 DNA 重新加入动力学进行了实验测量。关于快速和慢速 DNA 重新加入,TLK 模型参数通过模拟的初始 DNA 损伤进行了充分优化。优化的 DNA 重新加入速度与实验 DNA 重新加入速度合理一致。使用优化的 TLK 模型,Geant4-DNA 模拟现在能够预测 HSGc-C5 细胞的细胞存活和 DNA 重新连接动力学。使用模拟的初始 DNA 损伤对 TLK 模型参数进行了充分优化。优化的 DNA 重新加入速度与实验 DNA 重新加入速度合理一致。使用优化的 TLK 模型,Geant4-DNA 模拟现在能够预测 HSGc-C5 细胞的细胞存活和 DNA 重新连接动力学。使用模拟的初始 DNA 损伤对 TLK 模型参数进行了充分优化。优化的 DNA 重新加入速度与实验 DNA 重新加入速度合理一致。使用优化的 TLK 模型,Geant4-DNA 模拟现在能够预测 HSGc-C5 细胞的细胞存活和 DNA 重新连接动力学。


关键词:Geant4-DNA,DNA repair,cell surviving fraction Geant4-DNA,DNA修复,细胞存活分数

来源:MDPI https://www.mdpi.com/2072-6694/13/23/6046/htm

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