Modelling radiation-induced bystander effect and cellular communication

In the last 10 years evidence has accumulated on the so-called radiation-induced 'non-targeted effects' and in particular on bystander effects, consisting of damage induction in non-irradiated cells most likely following the release of soluble factors by the irradiated ones. These phenomena were observed for different biological endpoints, both lethal and non-lethal for the cell. Although the underlying mechanisms are largely unknown, it is now widely recognised that two types of cellular communication (i.e. via gap junctions and/or release of molecular messengers into the extracellular environment) play a pivotal role. Furthermore, the effects can be significantly modulated by parameters such as cell type and cell-cycle stage, cell density, time after irradiation etc. Theoretical models and simulation codes can be of help to improve our knowledge of the mechanisms, as well as to investigate the possible role of these effects in determining deviations from the linear relationship between dose and risk which is generally applied in radiation protection. In this paper three models, including an approach under development at the University of Pavia, will be presented in detail. The focus will be on the various adopted assumptions, together with their implications in terms of non-targeted radiobiological damage and, more generally, low-dose radiation risk. Comparisons with experimental data will also be discussed.