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RITCARD:辐射诱发的轨迹、染色体畸变、修复和损伤。

RITCARD: Radiation-Induced Tracks, Chromosome Aberrations, Repair and Damage.

机构信息

KBRWyle, Houston, Texas 77058.

NASA Langley Research Center, Hampton, Virginia 23681.

出版信息

Radiat Res. 2019 Sep;192(3):282-298. doi: 10.1667/RR15250.1. Epub 2019 Jul 11.

Abstract

Chromosome aberrations (CAs) are one of the effects of radiation exposure and can have implications for human health in the space environment, since they are related to cancer risk. In radiation research, chromosome aberrations are a convenient biomarker for carcinogenesis. To shed light on the formation and quality of chromosome aberrations in the space environment, many experiments and simulations have been performed using chromosome aberrations in human cells, induced by heavy ions, which are present in galactic cosmic rays (GCRs). In this work, the new simulation program, radiation-induced tracks, chromosome aberrations, repair and damage (RITCARD), is presented. This software program is based on the algorithm used in the NASA Radiation Track Image (NASARTI) model with some improvements. NASARTI and RITCARD are both comprised of four parts: a random walk (RW) algorithm for simulating chromosomes in a nucleus; a deoxyribonucleic acid (DNA) damage algorithm; a break repair process; and a function to assess and count chromosome aberrations. Prior to running RITCARD, the code, relativistic ion tracks (RITRACKS), is used to simulate detailed radiation track structure and calculate time-dependent differential voxel dose maps in a parallelepiped centered on a cell nucleus. The RITCARD program reads the pre-calculated voxel dose and locates the intersections between the voxels and the chromosomes that were simulated by random walk. Radiation-induced breaks occur strictly at these intersections with a probability that is a function of the voxel dose. When a break occurs in the random walk, the corresponding chromosome piece is cut into two fragments where each has a free end at the position of the break. RITCARD generates a collection of all fragments, free ends, and enlists free end pairs. In the next step, the algorithm simulates the time-dependent rejoining of free end pairs, using different probabilities for pairs originating from a given break (proper) or from different breaks (improper), which results in the formation of fragment sequences. By grouping these sequences, the program determines the number and types of aberrations, based on the same criteria used in our experiment. The new program is used to assess the yields of various types of chromosome aberrations in human fibroblast cells for several ions (H, He, C, O, Ne, Si, Ti and Fe) with energies varying from 10 to 1,000 MeV/n. The results show linear and linear-quadratic dose dependence for most chromosome aberrations types. The calculation results were compared with those obtained by fluorescence hybridization (FISH) experiments that were performed by our group. The simulations and experiments are in better agreement at lower LET. Regarding the simulation results, the coefficient of the linear part of the dose-dependence curve also peaks at an LET value of approximately 100 keV/lm, which evokes a relative biological effectiveness (RBE) peak found by other researchers.

摘要

染色体畸变(CA)是辐射暴露的影响之一,可能对太空环境中的人类健康产生影响,因为它们与癌症风险有关。在辐射研究中,染色体畸变是致癌作用的一个方便的生物标志物。为了阐明在太空环境中染色体畸变的形成和质量,许多使用重离子诱导的人类细胞染色体畸变的实验和模拟已经进行,重离子存在于银河宇宙射线(GCRs)中。在这项工作中,提出了新的模拟程序,即辐射诱导的轨迹、染色体畸变、修复和损伤(RITCARD)。该软件程序基于 NASA 辐射轨迹图像(NASARTI)模型中使用的算法,并进行了一些改进。NASARTI 和 RITCARD 都由四个部分组成:模拟核内染色体的随机漫步(RW)算法;脱氧核糖核酸(DNA)损伤算法;断裂修复过程;以及评估和计数染色体畸变的功能。在运行 RITCARD 之前,使用代码相对论离子轨迹(RITRACKS)来模拟详细的辐射轨迹结构,并计算以细胞核为中心的平行六面体中的时变微分体素剂量图。RITCARD 程序读取预先计算的体素剂量,并在随机漫步模拟的体素和染色体之间找到交点。辐射诱导的断裂仅在这些交点处发生,其概率是体素剂量的函数。当随机漫步中发生断裂时,相应的染色体片段被切割成两个片段,每个片段在断裂位置都有一个自由端。RITCARD 生成所有片段、自由端的集合,并列出自由端对。在下一个步骤中,算法使用不同的概率模拟来自给定断裂(适当)或不同断裂(不适当)的自由端对的时变连接,从而形成片段序列。通过对这些序列进行分组,程序根据我们实验中使用的相同标准确定各种类型的染色体畸变的数量和类型。新程序用于评估几种离子(H、He、C、O、Ne、Si、Ti 和 Fe)在 10 至 1000 MeV/n 能量范围内对人类成纤维细胞的各种类型染色体畸变的产额。结果表明,大多数染色体畸变类型的剂量呈线性和线性二次关系。计算结果与我们小组进行的荧光杂交(FISH)实验结果进行了比较。在较低 LET 下,模拟和实验的结果更为一致。关于模拟结果,剂量依赖性曲线线性部分的系数也在大约 100 keV/μm 的 LET 值处达到峰值,这引发了其他研究人员发现的相对生物效应(RBE)峰值。

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