Track structure calculations on hypothetical subcellular targets for the release of cell-killing signals in bystander...

Track structure studies using PARTRAC have been performed with the aim to investigate the possibility of revealing information on initiating targets and mechanisms of bystander effects mediated by signals released into the culture medium. Dependences on radiation dose have been assessed for alternative signal emission scenarios, defined by required energy deposits in a number of subcellular targets, mimicking e.g. mitochondria as hypothetical targets for the release of signals. The simulation results agree with target theory, and elucidate the characteristic dose for signal emission as a function of target topology, size and activation energy. The observed dose dependence of bystander cell kill in medium transfer experiments is not as steep as predicted by the considered simple signal emission scenarios with a single or even multiple hits to the hypothetical targets. This has been resolved by accounting for variations in cellular characteristics among the irradiated cells.