Integrated Modelling of Cell Responses after Irradiation for DNA-Targeted Effects and Non-Targeted Effects.

Intercellular communication after ionizing radiation exposure, so-called non-targeted effects (NTEs), reduces cell survival. Here we describe an integrated cell-killing model considering NTEs and DNA damage along radiation particle tracks, known as DNA-targeted effects (TEs) based on repair kinetics of DNA damage. The proposed model was applied to a series of experimental data, i.e., signal concentration, DNA damage kinetics, cell survival curve and medium transfer bystander effects (MTBEs). To reproduce the experimental data, the model considers the following assumptions: (i) the linear-quadratic (LQ) function as absorbed dose to express the hit probability to emit cell-killing signals, (ii) the potentially repair of DNA lesions induced by NTEs, and (iii) lower efficiency of repair for the damage in NTEs than that in TEs. By comparing the model results with experimental data, we found that signal-induced DNA damage and lower repair efficiency in non-hit cells are responsible for NTE-related repair kinetics of DNA damage, cell survival curve with low-dose hyper-radiosensitivity (HRS) and MTBEs. From the standpoint of modelling, the integrated cell-killing model with the LQ relation and a different repair function for NTEs provide a reasonable signal-emission probability and a new estimation of low-dose HRS linked to DNA repair efficiency.