基于Geant4-DNA模拟质子辐照线虫DNA链损伤的生物效应研究

Geant4-DNA-based simulation of the radiobiological effects of proton radiation-induced damage to DNA strands of Caenorhabditis elegans

目的使用Geant4-DNA工具包计算质子致线虫生殖细胞的DNA损伤产额及相对生物效能(RBE)值,探究质子辐照线虫的生物效应。方法使用Geant4-DNA工具包中希尔伯特曲线构建直径为20μm的线虫生殖细胞DNA模型;模拟100、50、20、5和2 MeV的质子辐射造成的DNA损伤,获得不同的物理构造函数、能量阈值(ET)模型和自由基清除距离与DNA双链断裂产额(YDSBs)的关系,并与生物学实验数据(20 MeV质子)进行对比验证。计算不同能量质子诱导DNA损伤的具体类型以及基于RBE_(DSB)数学模型的质子RBE_(DSB)值。结果在不同的物理构造函数、ET模型以及自由基清除距离3个参数下,质子诱导的DNA损伤分析结果表明,当选取构造函数2时,质子诱导的YDSBs最低,构造函数4和构造函数6诱导的YDSBs相差不大;随着单能ET的增加,质子诱导的YDSBs在逐渐降低;当自由基清除距离越长时,质子诱导的YDSBs越高。与生物实验数据对比结果表明,选取构造函数4、21.25 eV的单能ET模型以及9 nm的自由基清除距离时,其模拟结果与相关实验数据最接近,两者相差约8.3%。质子的RBE_(DSB)计算结果表明,其值在1.02~1.85范围内变化,质子能量越低,RBE_(DSB)越高。结论基于Geant4-DNA模拟质子诱导线虫的YDSBs与相关分子生物学检测结果吻合较好,为理解和预测质子辐射诱导的生物效应提供了重要手段。

Objective To calculate the yield and relative biological effectiveness(RBE)of proton radiation-induced DNA damage to C.elegans germ cells using the Geant4-DNA toolkit in order to explore the biological effects of proton radiation on Caenorhabditis elegans.Methods A DNA model for a 20-μm-diameter C.elegans germ cell was built using Hilbert curves within the Geant4-DNA toolkit.By simulating DNA damage induced by proton radiation at varying energy levels(100,50,20,5 and 2 MeV),the correlations between DNA double-strand break yields(YDSBs)and different parameters such as physics constructors,energy threshold(ET)models,and free radical scavenging distances were explored,and the result were compared with biological experimental data(20 MeV proton).The DNA damage types from varying energy levels of protons were defined,and the relative biological effectiveness of DNA double-strand breaks(RBE_(DSB))values were calculated using the RBE_(DSB)mathematical model.Results The analysis of proton radiation-induced DNA damage under varying physics constructors,ET models,and free radical scavenging distances indicated that the proton radiation-induced YDSBs were the lowest when physics constructor 2 was utilized,while the YDSBs under physics constructors 4 and 6 differed slightly.The proton radiation-induced YDSBs gradually decreased with a rise in both the single ET and free radical scavenging distance.The comparison revealed that the simulation result were the closest to biological experimental data under physics constructor 4,a single ET model of 21.25 eV,and a radical scavenging distance of 9 nm,with disparities approximating 8.3%.Calculated RBE_(DSB)values for protons spanned 1.02 to 1.85,with a lower proton energy corresponding to higher RBE_(DSB)values.Conclusions Proton radiation-induced YDSBs in C.elegans derived using Geant4-DNA simulations align well with relevant assessments using molecular biology.This study provides a vital means for understanding and predicting the biological effects stemming from proton radiation.