Mechanisms and implications of radiation-induced chromosome damage: an ab initio model and a Monte Carlo code

It is well known that cells exposed to ionizing radiation can develop chromosome aberrations (CAs), which consist of incorrect rejoining of chromatin fragments following breakage of the DNA double helix. This biological endpoint is extremely relevant, since CAs can lead both to cell death and, even more importantly, to cell conversion to malignancy. In particular, some leukaemia types are thought to arise from aberrations involving specific genes/chromosomes. Furthermore, aberrations can be used as “biological dosimeters” to monitor human exposure to radiation due to different reasons including environmental exposure, accidents and radiation therapy. Although many experimental data are available (especially in vitro), the mechanisms underlying chromosome aberration induction by radiation have not been fully clarified; theoretical models and codes can be of great help both for interpreting available data, and for performing predictions where the data are not sufficient. After reviewing the state of the art in the field, herein we will present a mechanistic, ab initio model and a Monte Carlo code that can now predict the induction of the main aberration types in human cells exposed to both photons and light ions; the implementation of heavy ions (including Carbon and Iron, which are of interest for hadron therapy and space research, respectively) is in progress, and preliminary results will be shown. The model basic assumptions and methods will be described, and comparisons with experimental data, which allowed for model validation, will be discussed. Furthermore, examples of applications will be shown, including Chronic Myeloid Leukaemia risk evaluation and prediction of chromosome aberrations in crewmembers of long-term space missions.