[Dynamics of proliferating cell populations during exposure to periodic phase-specific factors]

Dynamics of the numbers of population of proliferating cells under periodic phase-specific cytotoxic effect with and without blocking action was studied on the basis of a mathematical model. It has been shown that at real values of the model parameters after the beginning of the effects the population number exponentially depends of time. Dependence of the population number dynamics on integral parameters of the cell cycle and the exposure regime was studied. It has been shown that at certain periods a resonance decrease of the damage of the population cells must be observed. The values of the periods corresponding to the resonance decrease of the damage are determined mainly by the mean duration of the cell cycle and the time of blocking action, at small duration of the blocking action they are approximately multiple to the average time of the cell cycle. The theoretical predictions are proved experimentally in the experiments on determining the relationship between the damage of small intestine epithelium and mouse survival and the period of repeated periodic injections of S-phase-specific cytotoxic agent hydroxyurea. A distinct resonance increase of mouse survival and decreased damage of the epithelium were observed under the injections of oxyurea with the periods near to the mean and doubled mean time of the cell cycle of crypt enterocytes. The results obtained not only support the correctness of theoretical predictions, but make it possible to estimate the parameters of the stem cell cycle of mouse small intestine epithelium. They also show that this approach can be used for reducing aftereffects of chemotherapy by means of phase-specific agents.