不同能量质子物理作用过程致DNA损伤的对比研究

Comparisons of DNA damages in physics process caused by protons with different energies

目的基于蒙特卡罗程序包Geant4研究布拉格峰附近能量质子在物理作用过程阶段对DNA损伤的特点规律。方法利用Geant4构建细胞核及DNA模型，并基于Geant4-DNA物理过程模拟布拉格峰附近7档不同能量的质子在细胞核中传输过程，记录各相互作用位点相关信息，随机选取16％作用位点作为质子及其次级电子与DNA相互作用的位点，并将可导致DNA链断裂的位点信息写入新的文件，之后通过基于密度的空间聚类算法（DBSCAN）处理该文件，进而分析计算不同能量质子致DNA损伤的差异。结果能量介于0．6～20．0MeV之间的质子穿过细胞核时，随着能量的降低，单个质子致DNA损伤位点数由49．86增至549．88；损伤集簇数由2．92增至82．46；各尺寸集簇数增加显著，尺寸≥5的集簇增加329倍以上；平均集簇尺寸虽也有增加，但并不明显；简单单链断裂、复杂单链断裂、简单双链断裂和复杂双链断裂分别增加约7、25、23和63倍；单链断裂所占比例由96．69％减少到89．37％，双链断裂则由3．31％增加至10．63％。结论质子能量越低，通过物理作用过程使DNA产生的损伤越复杂，DNA的修复越困难。

Objective To compare the difference among DNA damages in physics processes caused by protons with different energies around Bragg peak. Methods By constructing the nucleus and DNA model using Geant4 and simulating the transportation processes of protons with different energies around Bragg peak in nucleus model based on Geant4-DNA, the information of interaction points were recorded. 16% of them were picked randomly to use as the points at which protons interact with DNA. After finding out the points which broke the DNA and writing their information to new files, these new files were treated with density-based spatial clustering of applications with noise （DBSCAN） , so as to analyze and calculate the difference of DNA damages caused by protons with different energies. Results With the protons with energies from 20.0 to 0.6 MeV, the numbers of damage points and damage clusters increased from 49.86 to 549.88 and from 2.92 to 82.46, respectively; the numbers of clusters with different sizes had a remarkable increase, and the number of clusters with size not less than 5 increased by 400 times. The average cluster size increased slightly. Simple single strand breaks （SSSBs） , complex single strand breaks （CSSBs）, simple double strand breaks （SDSBs） and complex double strand breaks （CDSBs） of DNA increased by about 8, 26, 24 and 64 times, respectively. The proportion of single strand breaks （SSBs） decreased from 96.69% to 89.37%, and the double strand breaks （DSBs） increased from 3.31% to 10.63%. Conclusions The lower proton energy would result in the more complex damage to DNA and the harder repair of DNA damage.