REVIEW OF QUANTITATIVE MECHANISTIC MODELS OF RADIATION-INDUCED NON-TARGETED EFFECTS (NTE).

Quantitative mechanistic modeling of the biological effects of ionizing radiation has a long rich history. Initially, it was dominated by target theory, which quantifies damage caused by traversal of cellular targets like DNA by ionizing tracks. The discovery that mutagenesis, death and/or altered behavior sometimes occur in cells that were not themselves traversed by any radiation tracks but merely interacted with traversed cells was initially seen as surprising. As more evidence of such 'non-targeted' or 'bystander' effects accumulated, the importance of their contribution to radiation-induced damage became more recognized. Understanding and modeling these processes is important for quantifying and predicting radiation-induced health risks. Here we review the variety of mechanistic mathematical models of nontargeted effects that emerged over the past 2-3 decades. This review is not intended to be exhaustive, but focuses on the main assumptions and approaches shared or distinct between models, and on identifying areas for future research.