Cytotoxic drugs timed administration

To clarify the reason why different circadian schedules of 5-FU delivery have distinct cytotoxic effects, we used the cell cycle automaton model to determine the time evolution of the fraction of cells in S phase in response to different patterns of circadian drug administration, for a cell cycle variability of 15%. The results, shown in Fig. 10.5, correspond to the case considered in Fig. 10.4, namely, entrainment of a 22-h cell cycle by the circadian clock. The data for Fig. 10.5a clearly indicate why the circadian schedule with a peak at 4 a.m. is the least toxic. The reason is that the fraction of cells in S phase is then precisely in antiphase with the circadian profile of 5-FU. Since 5-FU only affects cells in the S phase, the circadian delivery of the anticancer drug in this case kills but a negligible amount of cells. 

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