Bueno M, Schulte R, Meylan S, Villagrasa C
Institute de Radioprotection et de Sûreté Nucléaire, PRP/HOM-SDE-LDRI, BP 17, 92260 Fontenay aux Roses, France.
Phys Med Biol. 2015 Nov 7;60(21):8583-99. doi: 10.1088/0031-9155/60/21/8583. Epub 2015 Oct 26.
The aim of this study was to evaluate the influence of the geometrical detail of the DNA on nanodosimetric parameters of track structure induced by protons and alpha particles of different energies (LET values ranging from 1 to 162.5 keV µm-1) as calculated by Geant4-DNA Monte Carlo simulations.The first geometry considered consisted of a well-structured placement of a realistic description of the DNA double helix wrapped around cylindrical histones (GeomHist) forming a 18 kbp-long chromatin fiber. In the second geometry considered, the DNA was modeled as a total of 1800 ten bp-long homogeneous cylinders (2.3 nm diameter and 3.4 nm height) placed in random positions and orientations (GeomCyl). As for GeomHist, GeomCyl contained a DNA material equivalent to 18 kbp. Geant4-DNA track structure simulations were performed and ionizations were counted in the scoring volumes. For GeomCyl, clusters were defined as the number of ionizations (ν) scored in each 10 bp-long cylinder. For GeomHist, clusters of ionizations scored in the sugar-phosphate groups of the double-helix were revealed by the DBSCAN clustering algorithm according to a proximity criteria among ionizations separated by less than 10 bp. The topology of the ionization clusters formed using GeomHist and GeomCyl geometries were compared in terms of biologically relevant nanodosimetric quantities.The discontinuous modeling of the DNA for GeomCyl led to smaller cluster sizes than for GeomHist. The continuous modeling of the DNA molecule for GeomHist allowed the merging of ionization points by the DBSCAN algorithm giving rise to larger clusters, which were not detectable within the GeomCyl geometry. Mean cluster size (m1) was found to be of the order of 10% higher for GeomHist compared to GeomCyl for LET < 15 keV µm-1. For higher LETs, the difference increased with LET similarly for protons and alpha particles. Both geometries showed the same relationship between m1 and the cumulative relative frequency of clusters with v≥3 (f3) within statistical variations, independently of particle type. In order to obtain ionization cluster size distributions relevant for biological DNA lesions, the complex DNA geometry and a scoring method without fixed boundaries should be preferred to the simple cylindrical geometry with a fixed scoring volume.
本研究的目的是通过Geant4-DNA蒙特卡罗模拟，评估DNA的几何细节对不同能量的质子和α粒子（线能量转移值范围为从1至162.5 keV µm-1）所诱导的径迹结构纳米剂量学参数的影响。所考虑的第一种几何结构是将缠绕在圆柱形组蛋白周围的DNA双螺旋进行逼真描述的结构化排列（GeomHist），形成一条18 kbp长的染色质纤维。在考虑的第二种几何结构中，DNA被建模为总共1800个十个碱基对长的均匀圆柱体（直径2.3纳米，高3.4纳米），放置在随机位置和方向上（GeomCyl）。与GeomHist一样，GeomCyl包含相当于18 kbp的DNA材料。进行了Geant4-DNA径迹结构模拟，并在计分体积中对电离进行计数。对于GeomCyl，簇被定义为每个十个碱基对长的圆柱体中计分的电离数（ν）。对于GeomHist，根据由小于10个碱基对分隔的电离之间的接近标准，通过DBSCAN聚类算法揭示双螺旋磷酸糖基团中计分的电离簇。就生物学相关的纳米剂量学量而言，比较了使用GeomHist和GeomCyl几何结构形成的电离簇的拓扑结构。GeomCyl中DNA的不连续建模导致簇尺寸比GeomHist小。GeomHist中DNA分子的连续建模允许通过DBSCAN算法合并电离点，从而产生更大的簇，这在GeomCyl几何结构中是检测不到的。对于线能量转移值小于15 keV µm-1的情况，发现GeomHist的平均簇尺寸（m1）比GeomCyl高约10%。对于更高的线能量转移值，质子和α粒子的差异随线能量转移值的增加方式类似。在统计变化范围内，两种几何结构都显示出m1与簇数v≥3的累积相对频率（f3）之间具有相同的关系，与粒子类型无关。为了获得与生物DNA损伤相关的电离簇尺寸分布，与具有固定计分体积的简单圆柱形几何结构相比，应优先选择复杂的DNA几何结构和无固定边界的计分方法。
