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A pronounced increase of Bcl-2 content was observed in thymus of mice exposed to 20 cGy of gamma-radiation 1 and 24 hours after the exposure; six days after the exposure the bcl-2 content lowered to the control one. No changes in bcl-2 level were revealed in mice liver during the period of observation. A level of Bax protein was stable in mice thymus during 60 days of observation.

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After intraperitoneal injection of 100 or 198 mg/kg of human serum apotransferrin (apo TF) to mice 1 day before acute exposure to 6 Gy of gamma-radiation, the number of endogenous CFU in spleen (CFUs) increased 2.5 or 2.6 times respectively. At a dose fo 10 mg/kg of the protein only an increasing tendency was found, whereas a dose of 1 mg/kg was inefficient. A dose of 100 mg/kg of BSA did not show any effect suggesting that non-specific immune response to alien antigen did not contribute to apo TF radiomodifying action. The following mechanisms of the apoTF radiomodifying effect are discussed: 1) the ability of the protein to inactivate Fe3+ ions that reduces the consequences of radiation oxidative stress; 2) the stimulation of proliferation of the exposed bone marrow cells by activation of Fe3+ transport or by Ca2+ mediated mechanism of mitogen signal transduction; 3) changing in the content and ratio of cyclic nucleotides by apo TF stimulation of Ca-calmodulin-dependent phosphodiesterase.

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One day after the irradiation (dose 6 Gy) of mice protected by the injection of Zn-metallothionein (Zn-MT) in doze 8.6 mg/kg, 10-20 min before irradiation, then alpha-adrenomimetic indraline (150 mg/kg) 5-10 min before irradiation the increase in nucleic cell number, [3H] thymidine incorporation, and antioxidant activity in bone marrow in comparison with the control and indraline per se was revealed. In mice protected according to the scheme: Zn-MT in the same doze, then indraline (100 mg/kg) one day after, and then in 5-10 min exposure to 6 Gy it was found more than 9 times increase of endogeneous CFC in spleen on 8th day while indraline per se raised CFC number only 4.8 times. It was found that Zn-MT reduce the indraline acute toxicity. The data on radioprotective activity of monomeric and polymeric Zn-MT forms are submitted.

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The mechanisms of adaptive response (AR) which consisted of the increasing of cell and organism resistance to large doses of genotoxic and toxic agents formed after the preliminary influencing of its agents in small doses were discussed. The examples of factors leading to AR (irradiation, radiomimetics, alkylators, H2O2, and hyperthermy) as well as the conditions of its manifestation (in vivo and in vitro, acute and chronic adapting influences) were produced. The AR mechanisms bases on the molecular and cellular levels are the stimulation of protecting system (the synthesis of protecting proteins and antioxidant system activation), the intensification of DNA repair, effect on neurohumoral signal messengers and changes of proliferative activity. On organism level the nonspecific stress-reaction components were added (AKTG and steroid hormones synthesis). It was concluded that no there was no single mechanism of AR to all type of damaging agents. Evidently of that causes of its phenomenon have the complex character. The relatively narrow limits of AR (variability for the cells of different individuals, slight AR in children's cells and full absence of embryo cells) require careful use an AR conformities as the indicator for the professional and referring works.

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The data about the increasing of radioresistance of cells and organism after the acute, chronic and prolonged irradiation in vivo were presented. The possible mechanisms of adaptation to irradiation connected with selection, stimulation of proliferative activity, forming of protecting system (protected proteins, antioxidant enzymes e.a.), activation of DNA repair and cAMP-, and Ca(2+)-dependent phosphorylation systems were observed. The conclusion about complex mechanism of radiation adaptation was drawn.

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It was shown, that rat hepatic Zn-metallothionein (Zn-MT) depressed in vitro Fe3+/ADP-induced lipid peroxidation (LP) in rat bone marrow cells and increased its viability after pro-oxidant's influences. ZnCl2 and its combination with cysteine also decreased LP products level, but less and did not alter viability. On 9-th day after gamma-irradiation (6 Gy) in mice protected with Zn-MT the LP products level in bone marrow was decreased in considerable extent.

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Zn-MT and less apo MT (4-100 mkg/ml) in vitro stimulated the [3H]-thymidine incorporation in mice bone marrow cells, but ZnCl2, its combination with cysteine and mixture (ZnCl2 + cystine + albumin) inhibited DNA synthesis. In protected with Zn-MT (1-4 mg/kg) 10-15 min before irradiation (6 Gy) mice on 9th day after influencing the increasing of DNA replicative synthesis level and nuclear cell number in bone marrow were observed.

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It was shown that introduction of cadmium chloride (0.75 mg/kg Cd2+) in combination with gamma irradiation (8.5 Gy) of mice increases the level of metallothioneines (MTs) in the bone marrow and liver of mice. The maximum effect was observed in 24-30 h after the performance. Similarly, irradiation with the doses of 3 to 10 Gy resulted in an increase in the contents of both MT isoforms (MT1 and MT2) in the bone marrow in 24 h. A combined action of gamma irradiation and a heavy metal caused an additive effect on the MT content in the bone marrow, whereas the MT content in liver was 2 times lower than that predicted theoretically. A possible mechanism of the discovered phenomenon was discussed. Supposedly, it is associated with different degrees of the radiation-induced inhibition of the MT1 and MT2 expression by cadmium ions.

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Results of clinical application of method of non-contact periorbital electrostimulation in 6 groups of neurologic patients (total number-246) with optic nerve pathology of different origin (post-traumatic, hypertensive, inflammatory) are summarized. Analysis of interdependence between positive results and severity of visual disorders, type of the disease, responsible for partial atrophy of optic nerve, was performed. This method of restoration of vision in investigated patients proved to be effective both in hospitals and outpatient departments.

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To assess the possible functional role of single-strand DNA-binding (SSB) proteins in eucaryotic cell, a comparative study was made of SSB-proteins isolated from chromatin and the nonchromatin fractions of Ehrlich ascites tumour (EAT) cells. No appreciable differences between the two groups could be found either in SDS-gel electrophoretic patterns or in the ssDNA-binding capacity and stimulation of DNA replication in permeable EAT cells. However, the chromatin SSB-proteins incorporated 1.4-times more labelled phosphate in vivo; phosphate assays in the isolated chromatin and nonchromatin SSB-proteins yielded ca. 3 and 2 moles Pi/mole protein, respectively. Both preparations could be further phosphorylated in vitro with Ca-phospholipid-dependent protein kinase and the catalytic subunit of cAMP-dependent protein kinase, but the non-chromatin proteins were phosphorylated to a greater degree. In parallel with phosphorylation, the SSB-proteins displayed stronger binding to ssDNA cellulose. Phosphorylation may thus be a means of regulating the functions of SSB-proteins, in particular their interaction with chromatin.

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A comparative study of single-stranded DNA-binding proteins (SSB-proteins) isolated from chromatin and the extrachromatin fraction of Ehrlich ascites tumour cells was carried out. No differences were found either in SDS-gel electrophoretic mobility or in the single-stranded DNA-binding capacity and stimulation of the replicative synthesis of DNA. However, chromatin SSB-proteins contained 1.4-1.5 times more phosphate than extrachromatin proteins. Both preparations could be phosphorylated in vitro by protein kinase C and cAMP-dependent protein kinase, but the chromatin proteins were phosphorylated in a lesser degree. In parallel with phosphorylation the SSB-proteins displayed a higher binding affinity for ssDNA-cellulose. Phosphorylation can thus be regarded as a means of regulation of the SSB-protein function, in particular, their interaction with chromatin DNA.

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Vision conduction routes were examined in 75 patients with the syndrome of optic nerve partial atrophy by recording the visual evoked potentials, threshold of electric sensitivity emergence, critical frequency of phosphene disappearance, electroretino- and electroneurograms. The findings of these examinations correlated best of all with the clinical picture when visual evoked potentials (latency increase, decrease of the amplitude with atrophy augmentation, interhemispheric asymmetry in chiasmal and retro-chiasmal involvement) or the critical frequency of phosphene disappearance (reliably reduced if a disease was developing) were recorded. Introduction of electrodes with therapeutic and diagnostic purpose permitted assessment of optic nerve function from the electroneurogram amplitude and time parameters.

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The effect of different chemical compounds on the cAMP/cGMP ratio in the bone marrow of mice and radioresistance of animals has been studied. It has been shown that all compounds possessing radioprotective properties give rise to the cAMP/cGMP ratio in the bone marrow of mice. No changes in cAMP and cGMP level were noted after the administration of nonradioprotective substances. The maximal radioprotective effect coincide in time with the largest increase of the cAMP/cGMP ratio. The injection of radioprotectors at different doses demonstrate clearly that only at radioprotective doses the increase in the cAMP/cGMP ratio takes place. The administration of some substances 2, 15 and 60 min after the irradiation of mice shows that the radioprotective effect, though modest, was evident only in one case of elevated cAMP/cGMP ratio (the injection of 2-Mercaptoethylamine 2 min after the irradiation). Evident radioprotective effect occurs at the cAMP/cGMP ratio of about 170-200%; the ratio of about 130-140% corresponds to small radioprotection.

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A study was made of seven radioprotective agents of different chemical classes (sulfur-containing, indolylalkylamines, and imidazol, urea and pyridasine derivatives) and also of their six structural analogs without radioprotective properties on the content of cyclic nucleotides in blood plasma and on the postirradiation survival of mice. There was a correlation between the ability of the preparations to increase the level of cyclic adenosine-3',5'-monophosphate and their radioprotective properties; with guanosine-3',5'-monophosphate, this correlation was absent.

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The concentrations of cyclic nucleotides (cAMP and cGMP) were measured in blood plasma of dogs subjected to extracorporeal hemocarboperfusion. In spite of complete and irreversible absorption of cyclic nucleotides by the coal absorbent, SKN-2M, the concentration of cGMP in plasma remained within normal. The concentration of cAMP increased 1.5-2.5-fold. The rise in the cAMP concentration was not connected with injection of sodium thiopental and heparin before hemocarboperfusion. It is assumed that cyclic nucleotides play the role of circulating intercellular regulators in blood plasma. These regulators are necessary for the normal course of metabolic processes.

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