Models of the radiation-induced bystander effect

Purpose: To implement quantitative models of the Radiation-Induced Bystander Effects (RIBE) based on cellular excitation at a rate proportional to the concentration of signal molecules (called signals here) released by irradiated cells. Clonogenic cell survival and transformation frequency as a function of rescue time and dose were considered. Materials and methods: Our first stochastic model was based on the hypothesis that chemical signals are released into the extracellular medium by irradiated cells. These signals act on unirradiated cells switching them from the healthy to the dead state at rate R(t). We extended this model including a non-lethal transformed state in order to describe clonogenic cell survival and transformation frequency as a function of the number of alpha particles. Results: The first stochastic model was applied to an experiment on human keratinocyte (HaCat) cells yielding the half-life of at least one signal among the ensemble of possible candidates to trigger cell death in this cell culture. The second model yielded good fits to the data on clonogenic cell survival and transformation frequency in microbeam experiments with mouse embryo (C3H10T(1/2)) cells (Sawant et al. 2001a, 2001b). Conclusions: The fit of the first stochastic model to HaCat cell survival yielded a half-life of the order of minutes for possible signal candidates. This model also furnished the variance of the fraction of surviving cells.