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The effectiveness of fractionated exposure to gamma- and neutron radiation in their separate and combined use on the growth and functional morphology of mutant p53 sarcoma M-1 in rats was studied. Investigation techniques included immunostaining of PCNA and mutant p53 expressing cells, determination of mitotic activity and apoptotic death of tumor cells, as well as computer analysis of microscopic images. The antitumor efficacy of different types of radiation is shown to be determined by different levels of apoptosis induction, reduced proliferation and cellularity. Neutron radiation of the impulse generator has a marked damaging effect on the vasculature and the development of tumor necrosis. Fractionated irradiation at equal daily doses led to the decrease in the relative effectiveness of radio-inactivation of tumor cells. After 9 fractions of irradiation, the calculated value of the RBE of fast neutrons normalized to the input dose of 1 Gy by the coefficient of tumor growth inhibition, a reduced proliferative activity of PCNA and induced apoptosis of tumor cells was 3.4, 3.7 and 3.1, respectively. In the mode of daily superfractionation with splitting the dose in two fractions, the effectiveness of the combined exposure corresponded to the additive effect of gamma- and neutron radiation with a tendency toward synergism. There are reasons to believe that high resistance of sarcoma M-1 to the ionizing radiation impact is due not only to a fraction of hypoxic cells, but also the mutant status of p53 gene.

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Experimental investigations on rats have shown that development of dyshormonal immunodepression after ionizing radiation in sublethal doses depends on indirect effect of corticosteroids. Inhibition of steroidogenesis corrects ultrastructural lesions of the thymus after gamma irradiation.

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The paper reviews methods for studying functional morphology of endocrine cells histochemistry and immunohistochemistry, radioautography and methods of ultrastructural verification of secretory granules. Methodological approach is illustrated by the authors' results on the influence of ionizing radiation and tumor growth on the cells of the diffuse endocrine system.

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A study has been carried out to substantiate the assumption that excessive proliferation of major gastroduodenal endocrine cells may be predetermined genetically. Hereditary predisposition to the hyperplasia of cells belonging to the APUD system may be inherited both through the male and female lines. Duodenal ulcers (DU) undoubtedly involves multifactorial inheritance. Acquired capacity for endocrine cell hyperplasia cannot be excluded in some of DU patients. The development of DU is, apparently, related to the formation of a pathological system, based on pathologic structure-linked neurohormonal relationships between the duodenum and peripheral and central nervous systems that enhance nerve impulses in the duodenal bulbar portion. A sudden "total" catecholamine release occurs at a certain stage and is followed by a change of production/utilization ratios of various hormones that weakens pathologic neurohormonal relationships, destroys the pathologic system and activates the healing process around the ulcer. The pathologic system, active in peptic ulcers, is doubtless counteracted by a system, whose activity must be determined by the number of endocrine cells with beta-endorphine-like and, perhaps, serotonin-like immunoreactivity. The antagonistic regulation principle is of great universal significance for general biology. It is essential for healing and chronization processes.

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The time course of ultrastructural changes in the walls of arterial type vessels was studied in the small intestinal submucous membrane of Wistar male rats long after fractionated irradiation of the abdominal area. Three phases were identified in the development of vascular response to irradiation; mechanisms of their development are under discussion.

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Electron microscopy has revealed death of some of the apudocytes and recovery of the other ones in small intestine of rats after single total body irradiation in sublethal dose (5 Gy) and local fractionated irradiation (35 Gy, 7 Gy X 5) of the abdomen. The ability of EC-cells to form the autophagosomes was found. An absence of uniform reaction of different types of apudocytes to radiation is discussed.

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The use of highly sensitive and selective methods (autoradiography, light and electron microscopy, radioimmunoassay) allowed identification of peptide hormones in both the specialized endocrine cells (apudocytes) of some internal organs and various structural elements of the central and peripheral nervous system. Current knowledge permits one to suggest the existence of a peptidergic innervation as one of the parts of the nervous system and to demonstrate the direct participation of these peptides in the pathogenesis of some diseases. Biological significance of these substances in supporting homeostasis determines the urgent need for a combined investigation of the structural-functional relationship between apudocytes and peripheral nerves under normal and pathologic conditions. This will promote new opportunities in the elucidation of the mechanisms of some pathologic processes.

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The effect of vincristine treatment on the morphofunctional status of the small intestine was studied morphologically in 80 Wistar rats. The drug was found to possess a general toxic effect. Diarrhea was matched by the arrest of crypt cell-proliferation at metaphase, lysis, a decreased disaccharidase activity and increased levels of cytoplasmic alkaline phosphatase and dipeptidyl(amino)peptidase-IV in enterocytes of the villi. Exudation and degenerated cell organellae prevailed in intramural nervous ganglion cells, smooth muscle cells of intestinal tunica muscularis and vessels and in endothelium. The said changes were transitory in epithelium, but never regressed in nervous structures. At later stages (6-12 months after vincristine, but never regressed in endothelium. The later stages (6-12 months after vincristine treatment), secondary dystrophic changes developed in the small intestine wall, being predominantly confined to neuromuscular and vascular elements.

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The mucous membrane of the small intestine midportion of rats from the flight (weightless and centrifuged), synchronous and vivarium groups was examined electron microscopically. Ultrastructural changes were seen in all experimental groups, although their level and rate of recovery were different. Artificial gravity on Cosmos-936 did not influence those changes significantly. The data obtained suggest that the above changes are morphological manifestations of the reaction of rat small intestine to the combined effects of space flight factors.

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Acute toxicity of ethylphosphate, diethylphosphate and metaphosphate of S-ethylisothiuronium does not differ significantly when the drugs are administered to albino female mice intraperitoneally, intramuscularly or subcutaneously. However, this toxicity diminishes 4--5-fold during intragastric administration. The substances are approximately 100 mg/kg more toxic for Wistar rats as compared to mice. The radioprotective doses of the compounds administered intramuscularly ten times exert no effect on the rat behaviour, weight, peripheral blood composition, weight coefficients or histological structure of the internal organs.

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