Monte Carlo simulation of the production of short DNA fragments by low-linear energy transfer radiation using higher-order DNA models
Monte Carlo simulation of the production of short DNA fragments by low-linear energy transfer radiation using higher-order DNA models
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DOI：
10.2307/3579852
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发表时间：
1998-08-01
影响因子：
3.4
通讯作者：
Stork, T
中科院分区：
文献类型：
--
作者：
Friedland, W;Jacob, P;Stork, T
一个真实的 DNA 目标模型已经在生物物理模拟代码 PARTRAC 中开发和实现。它在原子水平上描述了哺乳动物细胞核内整个基因组的 B-DNA 结构的五个级别（核苷酸、DNA 螺旋、核小体、染色质纤维结构和染色质纤维环）。该模型能够描述规则的螺线管、交联体或之字形结构以及染色质纤维中核小体的重复随机排列。由能量高达 100 keV 的单能电子和 220 kVp X 射线产生的电子轨迹，从细胞中的随机位置开始，叠加在具有不同染色质纤维结构的四个 DNA 靶模型上。 SSB、DSB 以及短单链和双链 DNA 片段的产量是根据链原子的空间重合度确定的。该模型的两个参数——产生 SSB 所需的能量和将被评分为 DSB 的两个断裂之间的距离——被调整以等同于人成纤维细胞 X 射线照射后模拟和测量的链断裂产量。对于所有浓缩染色质纤维结构，短单链和双链片段的积分分数非常相似；他们同意低于 2 kbp 的 DNA 片段的实验数据。 0.1 至 1.5 kbp 范围内的模拟片段大小分布反映了纤维结构，与绞合度或电子能量无关。发现使用染色质纤维中核小体随机排列的分布比使用规则纤维结构获得的分布更符合实验数据。 (C) 1998 年，辐射研究会。
A realistic DNA target model has been developed and implemented in the biophysical simulation code PARTRAC. It describes five levels of the B-DNA structure (nucleotides, DNA helices, nucleosomes, chromatin fiber structure and chromatin fiber loops) on an atomic level for the whole genome inside a mammalian cell nucleus. The model is capable of describing regular solenoidal, crossed-linker or zigzag structures as well as repeating stochastic arrangements of nucleosomes in the chromatin fiber. Electron tracks resulting from monoenergetic electrons with energies up to 100 keV and from 220 kVp X rays, starting at random positions in the cell, were superimposed on four DNA target models with different chromatin fiber structures. The yields of SSBs, DSBs and short single- and double-stranded DNA fragments were determined from spatial coincidences with strand atoms. Two parameters of the model-the energy necessary to create an SSB and the distance between two breaks that would be scored as a DSB-were adapted to equate simulated and measured strand break yields after X irradiation of human fibroblast cells. The integral fractions of short single- and double-stranded fragments were rather similar for all condensed chromatin fiber structures; they agreed with experimental data for DNA fragments below 2 kbp. The simulated fragment size distributions in the range from 0.1 to 1.5 kbp reflected the fiber structure irrespective of strandedness or electron energy. The distributions using a stochastic arrangement of nucleosomes in the chromatin fiber were found to be in better accordance with experimental data than those obtained with regular fiber structures. (C) 1998 by Radiation Research Society.