Abstract
It has been reported that therapeutic value of cancer chemotherapy depends on a period of treatment time of the day. This effect, circadian time-dependency of treatment, has been considered to come from interactions between cell cycle and circadian rhythm. In this study, we aimed to clarify a biological background of this effect by means of simulating therapeutic effect based on a model of cell cycle controlled by circadian rhythms. Here we constructed a cell proliferation model using a framework of stochastic automaton. During the cell cycle process, a cell is subject to DNA damage with a certain probability. Then the damaged cell dies or returns to the cell cycle, causing a phase response to the cellular circadian clock system. In the simulations, a cancer cell is characterized by prolonged or shortened duration of G1 phase of the cell cycle. We simulated proliferation of 10,000 cells population treated by a drug that increases death rate of cells in S phase. As a result, we found that morning treatment is most effective to maximize the damage to the cancer cells and minimize the normal cell's death.
