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Circadian rhythm of DNA synthesis, mitotic activity, and duration of mitosis in rat liver were studied on days 3, 7, and 12 of life. Age-associated differences in the rhythmic parameters of these characteristics were detected. Epidermal growth factor plays an important role in the formation of cell proliferation rhythm in the early postnatal ontogeny and in the formation of proliferative hepatocyte pool.

Circadian rhythms of DNA synthesis, mitotic activity, and duration of mitosis in rat liver were studied on postnatal days 3, 7, and 12. Some age-related peculiarities of these rhythms were revealed. Epidermal growth factor was found to play an important role in the formation of cell proliferation rhythm during the early postnatal ontogeny and in the regulation of the pool of proliferating hepatocytes.

By means of autoradiography and metaphase arrest technique 24-hour rhythms and intensity of proliferative processes in the epithelium of gastric glands were studied, as well as morphometric status of these structures after vagotomy and drug sympathectomy in the rat. In both cases the reaction of glandular epithelium appeared with the increase of mitotic activity and the decrease of cell synchronization before the entry into DNA--synthesis and mitosis. The number of epithelial cells in gastric glands became reduced, but after vagotomy, unlike sympathectomy, mainly because of the lack of chief cells. Thus, the trophic control upon the dynamic structure of gastric glands may have different mechanisms of realization for parasympathetic and sympathetic nervous system, probably, through the influence on cell proliferation or differentiation.

Numbers of mitoses and of colchicine mitoses, and the duration of mitosis in corneal and tongue epithelium as well as in hepatocytes of intact and adrenalectomized rats have been studied in dynamics within 24 hours. In the control animals, the 24 hours rhythm of mitotic activity and the duration of mitosis were established. The length of mitosis falls during the high rate mitotic activity to increase when the number of dividing cells is reduced. Adrenalectomy results in decreasing the amplitude of mitotic activity fluctuations and in diminishing the amount cells entering mitosis during the 24 hours period. The rate of physiological regeneration in tissues of adrenalectomized animals is reduced. Different sensibilities of investigated tissues to adrenal cortex hormones deficiency have been revealed.

The amount of dividing and DNA-synthesizing cells was investigated in 22a hepatoma after injection of hepatic chalones to mice every 6 hours. Chalones were proved to lower sharply these indices, 3-6 h later they reach minimal values and remain at the lower level during the whole period of the investigation (27 h). Despite a pronounced inhibitory effect in the proliferating cell population there is a tendency to rhythmic proliferative processes. After cessation of prolonged (8 days) injections of the preparation the level of cell proliferation restores only by the 48th h after the last injection and the lifetime of animals with the tumour becomes twice as long. The preparation used possesses no immune properties.

Chalone isolated from the cells of the normal rat liver exerts a pronounced inhibitory action on hepatoma 22a cell division during 9 hours after its administration. Then the mitotic activity of hepatoma cells returns to the control level, but after 15 hours it starts to diminish again. The total amount of cells that entered the mitotic cycle during the experiment declined by 30% as compared to the control. Thus, hepatic chalone produces a reversible inhibition of hepatoma cell division in G2 and G1 phases of the mitotic cycle and lessens the fraction of dividing cells over a period of 24 hours.

Unilateral nephrectomy was performed in mice in the morning and in the evening. Mitotic activity in the proximal parts of the nephron tubules of the resting kidney and in the corneal epithelium was examined 48 and 60 hours after the operation. As compared with control, after the operation performed in the morning the mitotic index proved to increase 4.3 times and remained at a high level for 60 hours; after the operation performed in the evening mitotic index increased 9.3 times and decreased in 60 hours. It is concluded that the cells of the kidney epithelium entered into division more synchronously in the animals operated in the evening than in those operated in the morning. Nephrectomy had no influence on the level and rhythm of cell proliferation in the corneal epithelium.

The action of hepatic chalone on cell proliferation in inoculated hepatoma 22a of mice was studied in the presence of a changed level of glucocorticoid hormones in experimental animals. Chalone was obtained from the liver of intact rats by ethanol precipitation. The intensity of cell proliferation in hepatoma was evaluated by the colcemide and autoradiography methods. Six hours after chalone injection c-mitosis in the tumor decreased 2.7-fold, and the DNA index 6.8-fold. It may be concluded that the preparation used contains both G1- and G2-chalones. Single or repeated injections of hydrocortisone to mice inhibits cell proliferation to a less degree than administration of chalone alone. Combination of hydrocortisone and chalone produces the same effect as injection of chalone alone. Adrenalectomy diminishes susceptibility of hepatoma cells to exogenous chalone. The degree of tumor proliferative activity in the adrenalectomized animals was half as much after chalone injection, as compared to that in intact animals. Thus, a certain level of glucocorticoid hormones in hepatoma tissue is necessary to reveal the action of chalones.

In the work there was studied the influence of hepatic chalones on the level of mitotic activity and on the degree of adhesion of hepatocytes after the violation of parasympathetic and sympathetic innervation under the physiological conditions of liver function and in regenerating organ. Some definite regularities were revealed in the change of the power of linkage among the cells of liver parenchyma after the disturbance of its innervation and chalones affected. Significant differences in the effect of the influence of tissue inhibitors of proliferation on the process of regeneration in liver, which has intact or disturbed innervation were discovered. Particularly one can underline the effect of the loss of hepatocytes sensitivity to chalones in vagotomized liver.