Track structure calculations on intracellular targets responsible for signal release in bystander experiments with transfer of irradiated cell-conditioned medium

Abstract

Purpose: To investigate alternative scenarios for the dose-dependent emission of bystander signals by irradiated cells in medium transfer experiments.Methods: Energy deposition patterns to hypothetical intracellular targets whose hit by radiation initiates the emission of bystander signals have been simulated by Monte Carlo code PARTRAC, evaluating the effects of target size, multiplicity and threshold energy for activation. Scenarios in which individual irradiated cells release signals independently as well as those with signal amplification by neighbour cells have been analyzed. The non-linear response of unirradiated cells to signals in the transferred medium has been considered.Results: The experimentally observed dose dependence of bystander effects is consistent with cell-autonomous signal release with a wide distribution of characteristic doses, covering the range of 3 mGy to 3 Gy. Alternatively, the data can be explained by assuming that only cells receiving a high specific energy (3 Gy to 0.5 μm targets) release primary signals, which are then amplified by secondary signalling by neighbour cells within about a millimetre distance.Conclusion: Alternative signal emission scenarios are consistent with the observed dose dependence of bystander effects in medium transfer experiments. Thus, further experimental research is needed to identify the actual mechanism of bystander signal emission.