Cell response to chronc irradiation-modeling and simulation studies

A combined mathematical model of cellular radiation response and proliferation is constructed in order to study the effects on growth of low dose-rate chronic irradiation. The kinetic properties of the model are determined by computer solution of the rate equations. Model parameters for radiation response (including radiation-induced delay) and proliferation are determined for each stage of the cell cycle on the basis of acute irradiaton experiments with V79 Chinese hamster cells. The experimental data are very well simulated by the model. For the V79 cell system, exponential killing had to be included to fit the experiments in certain stages of the cell cycle. The few experimental chronic irradiation studies, carried out at moderately low dose rate with V79 cells, are reasonably well simulated by the above model. Similarities and differences between experimental results and computer simulations are discussed. The simple models show that, in the absence of exponential killing, an effective threshold is observable in the sense that the radiation effect versus dose curve starts with a very low slope which then increases rapidly. If exponential killing is present, the initial part of such a curve is linear in the dose, i.e., no threshold. The computer simulation for the V79 cells shows no threshold since exponential killing is included in the model. Dose rate effects are also discussed