Resonance effect in self-renewing tissues.

It was predicted previously that a depletion of cell population depends extremely on the period of periodic phase-specific killing of cells and at periods near the integer multiple of the mean cell-cycle time there is a considerable reduction in treatment-induced decrease of cell-population size (resonance effect). This paper is devoted to theoretical and experimental analysis of the resonance effect in self-renewing tissues. The main biological assumptions underlying the idea of the resonance effect are discussed and then reformulated in terms of a mathematical model.

[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.

[The resonance nature of the dependence of epithelial lesions of the small intestine in mice on the interval between injections of an S-phase-specific agent--hydroxyurea].

The dependence of the injury of murine small intestinal epithelium on the interval between multiple regular injections of hydroxyurea (HU) was investigated. Mice were injected 8 times with HU (5 mg per injection) in different experimental groups of animals, and the interval between injections varied from 6 to 19 hours. With the intervals between the injections close to 8 or 16.

[Significance of the intervals of hydroxyurea administration for epithelial damage to the small intestine in mice].

The states of the murine small intestinal epithelium 6, 30 and 78 h after the end of the multiple regular injections of hydroxyurea (HU) were analysed with the aid of the light and electron microscopy. The course of 6 regular injections of 5 mg/mouse HU was begun 24 h after the initiating gamma-irradiation in a dose 200 rad and the interval between injections was varied from 7 to 19 h for different experimental groups of mice. The analysis of the epithelial state revealed two minima of the tissue damage which correspond to the courses of HU injections with the intervals close 9 h and 16.

[Apoptosis and regeneration of enterocytes in experimental atrophy of the small intestine mucosa].

Apoptosis, one of the types of cell deaths, participates in regulating the size of regenerated tissue. Severe atrophy of small intestine mucosa in mice was caused by the administration of hydroxyurea solution. The degree of atrophy correlated with a lowering mitotic activity and DNA synthesis in the epithelium of crypts.