[Influence of indoinetophene on the antiradiation properties of indralin].

Radioprotective properties of indralin were studied at its combined administration with indometophene in the periods optimal for each preparation before acute radiation exposure. Animals were subjected to total radiation on the IGUR installation (137Cs): mice of the strain (CBA x C57B1) F1 at a dose of 9 Gy (LD100/30), purebred dogs--4 Gy (LD100/45). It was established in the experiments on mice that considerable radioprotective effect can be obtained by the use of indralin at a dose that is half the optimal radioprotective dose if it is applied against the background of indometophene administered at its optimal radioprotective dose four days before.

[The use of EPR spectroscopy to control the changes of organism radiosensitivity/radioresistance. Experimental and clinical results].

The responses of deoxyribonucleotide (dNTP), DNA and protein synthesis systems in blood-forming organs of animals (dogs, mice) as well as changes in Fe(3+)-transferrin (Fe(3+)-TF) and Cu(2+)-ceruloplasmin (Cu(2+)-CP) pools in blood to gamma-irradiation and the administration of radioprotectors have been studied. It has been shown that changes in Fe(3+)-TF and Cu(2+)-CP pools in blood are indices of changes in the body radioresistance and are reliably controlled by the EPR technique. An increase in the Fe(3+)-TF pool promotes the activated synthesis of dNTP, DNA and Fe(3+)-containing proteins which are essential for the repair efficiency during the early post-irradiation time as well as for the development of compensatory and restorative reactions of cellular systems; i.

Effect of hypoxia on the state of tissues in SAMR1 and SAMP1 mice with various rates of aging.

Senescence-accelerated SAMP1 mice were more sensitive to the negative effect of hypobaric hypoxia than SAMR1 mice (control). Low-temperature EPR spectroscopy showed that high sensitivity of SAMP1 mice is related to the increased concentration of methemoglobin in the blood leading to hemic hypoxia. Proton magnetic relaxation study showed that the exposure of SAMP1 mice to hypoxia can cause cerebral edema.

[The most important stages of the mechanism of action in vivo of carcinogen diethylnitrosoamine and its effect on the synthesis of RNA, proteins, DNA, and deoxyribonucleotides].

The mechanisms of nitric oxide (NO) generation from exogenous and endogenous sources, induced by the addition of the carcinogen diethylnitrosoamine (DENA) to rat organism have been studied. Within 15 h after the addition of DENA, the carcinogen itselt acts as an exogenous NO donor. The products of protein degradation (the process induced by DENA) act as endogenous donors of NO.

[The use of EPR spectroscopy to control the changes in organism radioresistance. Clinical results].

It has been shown that changes in Fe(3+)-transferrin and Cu(2+)-ceruloplasmin pools, which are trust-worthy controlled by the EPR technique in whole blood, blood plasma, and serum, as well as changes in the extracellular DNA content in blood plasma are markers of changes in organism radioresistance. This has been proved during the medical examination of the Chernobyl accident recovery workers and civil population, including children, exposed to low-intensity radiation, as well as during clinical investigation of new radioprotectors.

[The use of EPR spectroscopy to control the changes in organism radioresistance. Experimental results].

The responses of deoxyribonucleotide (dNTP), DNA, and protein synthesis systems in blood-forming organs of animals (dogs, mice) as well as changes in Fe(3+)-transferrin (Fe(3+)-TF) and Cu(2+)-ceruloplasmin (Cu(2+)-CP) pools in blood to gamma-irradiation and the administration of radioprotectors have been studied. It has been shown that changes in Fe(3+)-TF and Cu(2+)-CP pools in blood are indices of changes of body radioresistance and are reliably controlled by the EPR technique. An increase in the Fe(3+)-TF pool promotes the activation of synthesis of dNTP, DNA, and Fe(3+)-containing proteins, which are essential for repair efficiency during early post-irradiation time as well as for the development of compensatory and restorative reactions of cellular systems; i.

[The mechanisms of nitric oxide production from exogenous and endogenous NO-donating compounds and its effect on deoxyribonucleotide and DNA synthesis].

The mechanisms of exogenous nitric oxide (NO) production through in vivo biotransformation of nitro-, nitroso- and amino-containing substances were discussed. In addition, the mechanisms of production and cellular sources of endogenous NO, appearing in the blood and tissues after the exposure to various DNA-damaging factors, have been considered. Considerable quantities of endogenous NO were detected in the body in the first hours after translation inhibition by cycloheximide or animal exposure to superlethal radiation doses, i.

[The organization of medical aid to children of various cohorts of supervision, undergone to the influence of small dozes of radiation].

In clause the stages of organization of medical aid to children who undergone to the influence of the ecopathologic factors, including small dozes of ionizing radiation are submitted. The features of various stages of medical aid in nearest time after influence of the radiating agent are shown. The methodological complexities of diagnostic measures in the late times after the ecopathologic influence of small dozes of ionizing radiation are submitted, the role of the radiosensitivity in formation of pathological somatic diseases of condition at children is considered.

[Activation of deoxyribonucleotide synthesis by radioprotectants and antioxidants as a key stage in formation of body resistance to DNA-damaging factors].

The responses of the systems of synthesis of deoxyribonucleotides (dNTPs), DNA, and proteins in hematopoietic organs and liver of animals to gamma-radiation, administration of radioprotectants and antioxidants as well as the dependence of these responses on the doses of radiation and drugs were studied. Radioprotectants of acute (indralin) and durable effects (indomethaphen) as well as natural (alpha2-tocopherol) and synthetic anti-oxidants (ionol or 2,6-di-tert-butyl-4-methylphenol) efficient in survival test were used. Three stages could be recognized in the standard unspecific response of the studied systems to radiation: (1) immediate increase in ribonucleotide reductase activity in the tissues within the first 30 min as a part of the integrated SOS response to DNA damage, which activates dNTP synthesis; (2) inhibition of the synthesis of dNTPs, DNA, and and (3) restoring ribonucleotide reductase activity and integral increase in the production of dNTPs, DNA, and total protein, which is essential for the development of compensatory and restorative responses of the organism.

[Anabolic effect of natural and synthetic antioxidants].

The order of responses of cell systems of organs and changes in the content of some proteins of mouse and dog blood in response to addition of natural (alpha-tocopherol) and synthetic (ionol) antioxidants was studied at the whole-body level using ERP spectroscopy, radioisotope analysis, and chemiluminescence technique. Responses were evaluated by the temporary and concentration-dependence changes in the activity of ribonucleotide reductase and the rate of protein and DNA synthesis in organs of mice, as well as by the changes in the pools of Fe3+ -transferrin and Cu2+ -ceruloplasmin in blood and the antiradical activity of blood plasma of dogs and mice. During the first 24 h of exposure to alpha-tocopherol, the activity ribonucleotide reductase in bone marrow rapidly increased, whereas the activity of this enzyme and the rate of DNA synthesis in the thymus and spleen were suppressed by 30-50% compared to the control.

[Time- and dose-dependent post-irradiation changes of Fe3+-transferrin and Cu2+-ceruloplasmin pools in blood, their influence on ribonucleotide reductase activity in animal tissues and the effects of radioprotectors].

The time- and dose-dependent changes of Fe(3+)-transferrin (Fe(3+)-TF) and Cu(2+)-ceruloplasmin (Cu(2+)-CP) pools, of superoxide dismutase activity and the inhibitory activity of alpha 2-macroglobulin in blood as well as changes in synthesis rates of deoxyribonucleotides (dNTP), DNA and proteins in organs (spleen, liver, bone marrow, thymus) of mice and dogs given total body irradiation have been studied using of ESR spectroscopy, radioisotope techniques and biochemical determination of enzymatic activity. The experimental data have allowed us to reveal the sequence of organism's response reactions against irradiation and their modifications by radioprotectors. Changes in blood Fe(3+)-TF pool is one of the most informative, highly radiosensitive and rapidly reactive marker against irradiation and drug administrations.

[Reaction of rats organ cells to inhibition of protein biosynthesis by sublethal doses of cycloheximide].

Time-dependent responses of cellular systems in rat organs and Fe(3+)-transferrin and Cu(2+)-ceruloplasmin pools in blood to the blocking of translation by sublethal doses of cycloheximide (CHI) was studied by EPR spectroscopy and radioisotope techniques. It was shown that, within the early post-CHI-treatment time, the suppression of deoxyribonucleotide and DNA biosynthesis, the activation of catabolic enzymes, the inhibition of electron transfer in the mitochondrial electron transport chain, the activation and the following inactivation of cytochrome P-450, and an intensive production of nitrosyl complexes in rat blood and organs occur. In addition, the activation of the synthesis of steroid hormones in adrenal gland was revealed within 1-24 h after cycloheximide injection.

[Reactions of deoxyribonucleotide synthesis system to irradiation and their modification by radioprotectors].

The paper covers the problem on reactions of deoxyribonucleotide (dNTP) synthesis system in blood-forming organs of animals induced by irradiation. The synthesis of dNTP is a rate-limiting stage for DNA synthesis. Cellular requirements for dNTP pools during DNA synthesis are related with ensuring of the accuracy of DNA copying during replication and repair.

The activation of ribonucleotide reductase in animal organs as the cellular response against the treatment with DNA-damaging factors and the influence of radioprotectors on this effect.

Cellular requirements for deoxyribonucleotide (dNTP) pools during DNA synthesis are related to ensuring of the accuracy of DNA copying during replication and repair. This paper covers some problems on the reactions of dNTP synthesis system in organs of animals against the treatment with DNA-damaging agents. Ribonucleoside diphosphate reductase (NDPR) is the key enzyme for the synthesis of dNTP, since it catalyses the reductive conversion of ribonucleotides to deoxyribonucleotides.

[Fungal infection of human organs by resistant melanin-synthesizing species is one of the pathogenic factors and one of the real consequences of the accident at Chernobyl power plant].

Free radical melanin centers have been detected in the cell concentrate of bronchoalveolar lavage (BAL) of liquidator of Chernobyl NPP accident. To identify the nature of these centers the EPR technique and the fluorescent technique were used to study BAL of liquidators with lung chronic pathology, their blood, blood components as well as model melanin- and lipofuscin-containing systems: synthetic DOPA-melanin, human melanosome, human lipofuscin, human melanolipofuscin. I Besides that we have investigated the samples of fungi, extracted from lung phlegm of liquidators (Aspergillus niger, Aspergillus fumigatus, Aspergillus flavus, Penicillium Sp.

[The molecular mechanisms of the action of the radioprotector indometafen. The biosynthetic and bioenergetic aspects].

It was shown that indomethaphen (IM) is capable of stimulation of the synthesis of DNA, RNA, and protein precursors in mice. The IM-induced elevated level of the ribonucleotide reductase activity and, hence, deoxyribonucleotide pool in the spleen at the moment of irradiation and during the early postradiation period provides for complete DNA repair. As a result, the damaging effect of ionizing irradiation is weakened.

[Markers of the metabolic changes arising as a result of ionizing radiation exposure].

Time-related changes have been studied in the content of extracellular DNA, Fe(3+)-transferrin (TF), and Cu(2+)-ceruloplasmin (CP) in the blood plasma and the activity of ribonucleotide reductase (RR) in the tumor cells and spleen of mice during the development of acute lympholeukosis P-388 and after ionizing irradiation. At the initial stages of leucosis P-388, the content of extracellular DNA increases, the TF and CP pools in the blood plasma enlarge, and the RR activity in the tumor cells and spleen of tumoral mice markedly increases. A dose-dependent increase in RR activity was also recorded in the spleen of 5-day-old rats within 15-30 min after irradiation.

[Rapid metabolic changes in the blood and organs of rats under the influence of electron pulse radiation at superhigh doses].

Early metabolic changes have been studied in the peripheral blood, brain, adrenals, spleen, and liver of rats after irradiation with 500 Gy. Using ESR spectroscopy we showed the formation of a great amount of hemoglobin nitrosyl complexes and methemoglobin in the blood and spleen, thus suggesting that the endothelium-derived relaxing factor, nitric oxide (NO), was released due to irradiation stimulation and sharp hypoxia in brain. Polarographic data concerning the disturbance of brain mitochondrial function (activation of succinate hydrogenase oxidation) allowed a conclusion that hypoxia appeared after irradiation at superlethal doses.

[The molecular aspects of the action of the radioprotector indralin].

The effect of indralin on the metabolic parameters in peripheral blood and organs of irradiated dogs and mice have been studied by EPR, NMR and radioisotope methods. It has been shown that indralin stimulated biosynthesis of DNA precursors as well as of DNA and proteins in the organs and stabilized the rate of ATP and glycogen synthesis. As a result indralin reduced considerably the changes produced by gamma-irradiation on the macromolecular biosynthesis during the early post-irradiation period.

[The dose dependence of the development of compensatory-restorative body reactions to irradiation. The EPR method].

The study deals with the mechanism of organism's adaptive responses to the effect of radiation in widely ranging dose. Post-irradiation metabolic changes were evaluated in canine blood as well as in murine blood, spleen, bone marrow and liver using the EPR spectroscopy. It was shown that the dynamics of changes in transferrin and ceruloplasmin pools and ribonucleotide reductase activity were phase-dependent with the maxima at the 2nd, 6th and 10-12th days after irradiation.

[Ribonucleotide reductase--a "target" of the action of nitrosomethylurea].

The antitumor and toxic effects of methylnitrosourea (MNU) are determined through its metabolic pathways. In organism MNU is subject to hydrolytic decomposition and denitrosation. It has been shown in vivo studies that MNU abdominal injections of therapeutic doses caused the inhibition of ribonucleotide reductase in mouse spleen, and therefore the DNA synthesis depress.