A Mathematical model of the radiation-induced intercellular-signaling and cell-cycle response

Hattori, Yuya; Suzuki, Michiyo; Funayama, Tomoo; Kobayashi, Yasuhiko; Yokoya, Akinari; Watanabe, Ritsuko

Cell-to-cell communication is one of the important factors to understand the mechanisms of radiation-induced responses such as radiation-induced bystander effects at low doses. However, the involvement of the radiation-induced intercellular-signaling has not been established. In the present study, we propose simulation-based analyses of the intercellular signal transmissions between the individual cells in the cellular population. We modeled the transmissions of two types of signals, i.e., X is transmitted via culture medium and Y is transmitted via gap junctions. The cellular population was described by the grids, and the concentrations of the transmitters, X and Y, were calculated by each grid based on the diffusion equation. To observe the radiation-induced response of the cell caused by the signals, X and Y, we focused on the cell cycle. The cell cycle was modeled as a virtual clock including several check-point pathways and the cyclic process (G1, S, G2, M phases). The signals, X, Y, were transmitted to the cells and stopped the clocks at the check points. In the non-irradiated simulations, the change of cell cycle in our model was similar to that of the experimental data. Furthermore, the radiation was modeled as the radiation signal, Z, which affected the clock and the signals, X and Y. We input the radiation signal, Z, to specific cells, and simulated the behaviors of the clock of each cell and signals, X and Y. We will discuss the radiation-induced damages of the individual cells based on the simulations of the intercellular signaling and the cell cycle.