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We present a theoretical agent-based model of cell evolution under the actionof cytotoxic treatments, such as radioteraphy or chemoteraphy. The majorfeatures of cell cycle and proliferation, cell damage and repair, and chemicaldiffusion are included. Cell evolution is based on a discrete Markov chain,with cells stepping along a sequence of discrete internal states from 'normal'to 'inactive'. Probabilistic laws are introduced for each type of event a cellcan undergo during its life cycle: duplication, arrest, apoptosis, senescence,damage, healing. We adjust the model parameters on a series of cell irradiationexperiments, carried out in a clinical LINAC at 20 MV, in which the damage andrepair kinetics of single- and double-strand breaks are followed. Two showcaseapplications of the model are then presented. In the first one, we reconstructthe cell survival curves from a number of published low- and high-doseirradiation experiments. We reobtain a very good description of the datawithout assuming the well-known linear-quadratic model, but instead including avariable DSB repair probability, which is found to spontaneously saturate withan exponential decay at increasingly high doses. As a second test, we attemptto simulate the two extreme possibilities of the so-called 'bystander' effectin radiotherapy: the 'local' effect versus a 'global' effect, respectivelyactivated by the short-range or long-range diffusion of some factor, presumablysecreted by the irradiated cells. Even with an oversimplified simulation, wecould demonstrate a sizeable difference in the proliferation rate ofnon-irradiated cells, the proliferation acceleration being much larger for theglobal than the local effect, for relatively small fractions of irradiatedcells in the colony.

A biophysical model of cell evolution after cytotoxic treatments: damage, repair and cell response