Quantification of DNA double-strand breaks using Geant4-DNA.

Quantification of DNA double-strand breaks using Geant4-DNA.
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DOI:
10.1002/mp.13290
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发表时间:
2019-01
期刊:
影响因子:
3.8
通讯作者:
Kagadis GC
Kagadis GC
中科院分区:
医学3区
文献类型:
--
作者:
Chatzipapas KP;Papadimitroulas P;Obeidat M;McConnell KA;Kirby N;Loudos G;Papanikolaou N;Kagadis GC

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本研究旨在通过使用先进的蒙特卡罗工具包和新引入的DNA双链断裂测量实验方法,标准化测量DNA双链断裂(DSB)的模拟过程。为了对DNA DSB进行实验定量,采用了一种新型的DNA剂量计来产生实验数据。利用GATE和Geant4‐DNA工具包来模拟实验环境。对Geant4‐DNA的PDB4DNA样本进行了升级和研究。根据剂量,评估了模拟的参数,如链断裂的能量阈值(ET)和DSB的碱基对阈值(BPT)。模拟结果表明,当ET = 19±1 eV和BPT = 10 bp时,与实验数据的差异最小,而当ET<17.5 eV或ET bb0 22.5 eV和BPT = 10 bp时,与实验数据的差异较大。ET = 17.5 eV和BPT = 6 bp的差异也较小。不确定性一直保持在3%以下。这项研究包括DNA双链断裂定量的第一个结果。模拟了LINAC的能谱,并首次将其用于辐照DNA分子。模拟结果在原型DNA剂量计产生的实验数据上得到验证。
This study aims to standardize the simulation procedure in measuring DNA double‐strand breaks (DSBs), by using advanced Monte Carlo toolkits, and newly introduced experimental methods for DNA DSB measurement. For the experimental quantification of DNA DSB, an innovative DNA dosimeter was used to produce experimental data. GATE in combination with Geant4‐DNA toolkit were exploited to simulate the experimental environment. The PDB4DNA example of Geant4‐DNA was upgraded and investigated. Parameters of the simulation such energy threshold (ET) for a strand break and base pair threshold (BPT) for a DSB were evaluated, depending on the dose. Simulations resulted to minimum differentiation in comparison to experimental data for ET = 19 ± 1 eV and BPT = 10 bp, and high differentiation for ET<17.5 eV or ET>22.5 eV and BPT = 10 bp. There was also small differentiation for ET = 17.5 eV and BPT = 6 bp. Uncertainty has been kept lower than 3%. This study includes first results on the quantification of DNA double‐strand breaks. The energy spectrum of a LINAC was simulated and used for the first time to irradiate DNA molecules. Simulation outcome was validated on experimental data that were produced by a prototype DNA dosimeter.
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