Modeling radiation effects at the tissue level

For the understanding of radiation action in humans, a synergistic approach of experiments and quantitative modeling of working hypotheses is necessary. A large set of experimental data at the single-cell level are available, and biophysical modeling of radiation action has so far mostly concentrated on the first phases of radiation interaction with the biomolecules, and later biochemical stages including DNA breakage, repair, and the formation of chromosomal aberrations. The models can be extended to cell killing and transformation, but so far still using a single-cell (clonal expansion) approach. On the contrary, new experimental evidence points to the microenvironment and the tissue level as a critical radiation target for late effects, and to epigenetic and signaling mechanisms as mediators of radiation damage. This higher structural level is generally ignored in modeling, owing to its complexity and to the lack of experimental data. In this paper we will highlight the requirements for specific experimental approaches targeting the tissue/microenvironment level and the most promising available experimental models. © 2010 EDP Sciences, SIF, Springer-Verlag Berlin Heidelberg.