利用 TOPAS-nBio 对伽马射线诱导的 DNA 链断裂中的氧效应进行建模。

IF 3.3 3区 医学 Q2 ENGINEERING, BIOMEDICAL Physics in medicine and biology Pub Date : 2024-10-25 DOI:10.1088/1361-6560/ad87a7
Naoki D-Kondo, Thongchai A M Masilela, Wook-Geun Shin, Bruce Faddegon, Jay LaVerne, Jan Schuemann, Jose Ramos-Mendez
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引用次数: 0

摘要

提出并验证一种方法,利用蒙特卡洛轨道结构代码 TOPAS-nBio 从第一原理上模拟氧对辐射诱导的双链断裂(DSB)的影响。 在 TOPAS-nBio 中,通过考虑 DNA 的氧加成态和创建氧与辐射防护分子 WR-1065 之间的竞争动力学机制,建立了两个基于氧固定假说的化学模型。我们将这些模型命名为 "简单 "和 "详细",因为它们处理氢抽取途径的方式不同。我们使用简单模型为详细模型获取-OH-DNA 取氢途径概率的额外信息。我们对这些模型进行了校准,并与已发表的实验数据进行了比较,这些数据是用 R6K 质粒悬浮在作为羟基清除剂的二氧六环中,并用 137Cs 伽马射线照射后得到的线性和超卷曲部分的数据。WR-1065 和 O2 与 DNA 的反应速率取自实验结果。在不同的氧气浓度[O2](0.021%-21%)下,得到了单链断裂(SSB)和DSB与剂量的函数关系。 两种模型的超卷曲质粒和线性质粒部分的验证结果与实验趋势一致,误差在 12% 以内。HRF 与 137Cs 和 200-280 kVp x 射线的测量结果一致,误差在实验不确定范围内。然而,氧浓度为 2.1% 时的 HRF 高估了实验结果 1.7  0.1 倍。将 WR-1065 的浓度从 1 毫摩尔提高到 10-100 毫摩尔后,HRF 相差 0.01,在 TOPAS-nBio 和实验数据之间 0.08 的统计不确定性范围内。这凸显了使用这些化学模型重现实验 HRF 结果的可能性。 结果支持氧固定假说,认为氧和化学 DNA 修复分子(如 WR-1065)之间的竞争是氧放射增敏效应的主要原因。
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Modeling the oxygen effect in DNA strand break induced by gamma-rays with TOPAS-nBio.

Objective.To present and validate a method to simulate from first principles the effect of oxygen on radiation-induced double-strand breaks (DSBs) using the Monte Carlo Track-structure code TOPAS-nBio.Approach.Two chemical models based on the oxygen fixation hypothesis (OFH) were developed in TOPAS-nBio by considering an oxygen adduct state of DNA and creating a competition kinetic mechanism between oxygen and the radioprotective molecule WR-1065. We named these models 'simple' and 'detailed' due to the way they handle the hydrogen abstraction pathways. We used the simple model to obtain additional information for the •OH-DNA hydrogen abstraction pathway probability for the detailed model. These models were calibrated and compared with published experimental data of linear and supercoiling fractions obtained with R6K plasmids, suspended in dioxane as a hydroxyl scavenger, and irradiated with137Cs gamma-rays. The reaction rates for WR-1065 and O2with DNA were taken from experimental works. Single-Strand Breaks (SSBs) and DSBs as a function of the dose for a range of oxygen concentrations [O2] (0.021%-21%) were obtained. Finally, the hypoxia reduction factor (HRF) was obtained from DSBs.Main Results.Validation results followed the trend of the experimental within 12% for the supercoiled and linear plasmid fractions for both models. The HRF agreed with measurements obtained with137Cs and 200-280 kVp x-ray within experimental uncertainties. However, the HRF at an oxygen concentration of 2.1% overestimated experimental results by a factor of 1.7 ± 0.1. Increasing the concentration of WR-1065 from 1 mM to 10-100 mM resulted in a HRF difference of 0.01, within the 8% statistical uncertainty between TOPAS-nBio and experimental data. This highlights the possibility of using these chemical models to recreate experimental HRF results.Significance.Results support the OFH as a leading cause of oxygen radio-sensitization effects given a competition between oxygen and chemical DNA repair molecules like WR-1065.

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来源期刊
Physics in medicine and biology
Physics in medicine and biology 医学-工程:生物医学
CiteScore
6.50
自引率
14.30%
发文量
409
审稿时长
2 months
期刊介绍: The development and application of theoretical, computational and experimental physics to medicine, physiology and biology. Topics covered are: therapy physics (including ionizing and non-ionizing radiation); biomedical imaging (e.g. x-ray, magnetic resonance, ultrasound, optical and nuclear imaging); image-guided interventions; image reconstruction and analysis (including kinetic modelling); artificial intelligence in biomedical physics and analysis; nanoparticles in imaging and therapy; radiobiology; radiation protection and patient dose monitoring; radiation dosimetry
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