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

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 (1H+, 4He2+, 12C6+, 16O8+, 20Ne10+, 28Si14+, 48Ti22+ and 56Fe26+) 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 in situ 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.