A dynamic mathematical model for sub-lethal damage recovery: integrating recovery processes into multi-target theory...

Quantifying the biological effects of radiation is essential for radiotherapy and radiation protection. While research has centered on statistical analyses of experimental data, this approach often fails to elucidate underlying mechanisms, limiting the development of generalizable models. Describing time-dependent phenomena, such as sub-lethal damage (SLD) recovery during fractionated irradiation, presents a particularly significant challenge for existing static models. To address this, we developed a mechanistic mathematical model that extends the classical multi-target, single-hit model by introducing explicit recovery transitions among damage states, allowing the simultaneous description of radiation-induced damage accumulation and biological recovery. We applied this model to Elkind and Sutton's classical split-dose experimental data to determine its parameters. The model reproduced the major features of split-dose survival curves for treatments with 0-, 2.5-, and 23-hour recovery intervals. We visualized the temporal changes in damage state distributions within the cell populations. These simulations provided a process-level interpretation of the characteristic shoulder-like response appearing after an inter-fraction recovery interval. Furthermore, the estimated recovery half-life was ∼120 min, which is broadly consistent with reported timescales of DNA double-strand break repair in mammalian cells, supporting the biological interpretability of the model parameters. The proposed framework provides a simple, interpretable description of radiation-induced cell death dynamics, including SLD recovery, and may serve as a basis for the improved mechanistic modeling of radiobiological effects under different irradiation protocols.