Finally, using the proposed model, we evaluated the relationship between apoptosis induction and the number of p53 pulses, and we discussed the effects of stochasticity in the generation of IRinduced DSB, DSB repair system, and p53 signaling network on cell fate decision. This paper focused on theoretically demonstrating that the fluctuation of intranuclear biochemical reaction processes in cells is a major factor creating unknown criteria of cell fate decisions. In Figure 4B, ATM-P was elevated following IR irradiation, and a single pulse of ATM-P and phosphorylated p53 was generated. Examples of simulations that generated two and three phosphorylated p53 pulses are shown in Figure 4C and 4D, respectively. Discrepancies in the number of p53 pulses observed in Figure 4 correspond to the variability of p53 dynamics. Moreover, simulations with the IR dose set to 0.3 and 6 Gy are shown in Figures S4 and S5, respectively, in supporting information. This is in qualitative agreement with the simulated results shown in Figure 4. Despite application of the same IR dose, comparison of the time courses of levels of intranuclear components in cells showed discrepancies in the number of p53 pulses, as shown in Figure 4, Figures S4, and S5. Lahav et al. previously reported that in experiments using the MCF7 cell line, individual cells in the same population generated different numbers of p53 pulses following IR irradiation. Batchelor et al. demonstrated that Evofosfamide CYP17 inhibitor several components in the p53 signaling network, including p53, ATMP and Mdm2, exhibited oscillation. Our simulated results based on the proposed model are in good qualitative agreement with these biological findings. They introduced variable kinetic parameters into the model to fit their simulations to experimentally observed data. Though Zhang et al. reproduced variability of p53 pulses by considering only fluctuations in DSB generation and repair, there was no report on which their simulated results were in good agreement with any biological finding. The proposed model with fluctuation in only DSB generation and repair could not realize observed fractions of p53 pulses. However, our simulations with fluctuations in both DSB generation and repair and intranuclear reactions were quantitatively consistent to experimentally observed data. These results showed that the fluctuations in the abundance of both intranuclear chemical species and DSB play an important role as the source of noise. Next, the dynamics of p53 pulses at the cell population level were examined. Figure 6 shows the time courses of total p53 for populations of 1000 cells subjected to an IR dose of 0.3, 2.5, or 6 Gy. p53 oscillations were damped at each IR dose. At the cell population level, an increment in the IR dose increased the number of p53 pulses as well as the amplitude of the first p53 pulse. Bar-Or et al. reported that both p53 and Mdm2 exhibited damped oscillation in a population of NIH3T3 cells subjected to IR irradiation, and the amplitude of oscillation was dependent on the IR dose ; our simulated results shown in Figure 6 are in agreement with these findings.