[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 survival of mice increased on the average by 30-35% and provided the same effect of protection as a single indralin at the optimal radioprotective dose (100 mg/kg). The survivability of dogs after the combined application of the two radioprotectors makes up 43% against 14% after application of only indralin at a dose of 5 mg/kg (half the optimal radioprotective dose). Indometophene, along with strengthening the antiradiation activity of indralin at the ineffective (half the optimal) dose, allows the reduction of its undesirable postradiation effects in the hemopoietic tissue. The important role in the mechanism of the antiradiation activity of indometophene and indralin belongs to the increased ribonucleotide reductase activity and induction of the ribonucleotide synthesis that provides effective reparation of the damage to the DNA of the cells in radiosensitive tissues and organs as a result of administration of protective doses of radioprotectors at the optimal doses before radiation exposure.

[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.e., they are responsible for the body resistance to DNA-damaging factors. It is important that the intensity of responses depends on the initial state of the organism. 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 the changes in the extracellular DNA content in blood plasma are the markers of the changes in the 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.

[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. It was shown that the generation of nitric oxide from diethylnitrosoamine leads to deep hemic and tissue hypoxia and induces the inactivation of oxygen-dependent enzymes, including ribonucleotide reductase, and the inhibition of ATP synthesis. Under these conditions, the protein synthesis and as a consequence the synthesis of deoxyribonucleotides and DNA are strongly suppressed; i.e., diethylnitrosoamine produces the effect similar to the action of the antibiotic cycloheximide, an inhibitor of translation. The administration of cycloheximide to the animal organism also led to the appearance of a considerable amount of nitric oxide in the blood. It is assumed that nitric oxide initiates (on the administration of the carcinogen) or at least enhances (on the administration of cycloheximide) the blockage of the synthesis of the protein, deoxyribonucleotides, and DNA. In response to the disturbance of protein synthesis, the complex of enzymes is activated that accomplish the utilization of the degradation products of proteins, including the inducible form of NO synthase.

[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.e., they are responsible for body resistance to DNA-damaging factors. It is important that the intensity of responses depends on the initial state of the organism. Thus, dogs with initial individual characteristics of blood typical for "suppressed" or "activated" states had abnormally high responses to irradiation by low doses of 0.25 and 0.5 Gy. This fact is important for the estimation of consequences of prolonged low-dose irradiation for human population. It has been shown that radioprotectors, efficient in survival test activate the synthesis of dNTP, DNA, and proteins in organs. The intensity of dNTP synthesis and the time when dNTP pools get maximum values determine the efficiency of protectors and the time of irradiation after their administration.

[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.e., after the exposure to factors inducing destructive processes. The time and dose dependences of exogenous and endogenous NO production have been established. NO produced after a single or repeated administration of NO-donating compounds as well as endogenous NO proved to inhibit deoxyribonucleotide (dNTP) and DNA synthesis in animal tissues. Nonspecific compensatory responses to disturbed protein homeostasis included cyclic production of endogenous NO. The maximum levels of nitrosyl complexes were registered when the rate of protein synthesis decreased. The role of polyamines in the induction of macromolecule biosynthesis is discussed and NO production from these arginine-rich compounds is proposed. NO is released at the stage of polyamine inactivation. The inactivation mechanism includes the hydroxylation of aminogroups by NO synthase, the formation of nitroso intermediates, and their denitrosation with NO release.

[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. The opportunity of the differential treating and preventive help rendering to the children various cohorts of supervision is shown.

[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. The radioprotectants significantly increased ribonucleotide reductase activity, which increased intracellular concentrations of the four dNTP types in organs during radiation exposure and three following days. Within this period, ribonucleotide reductase activity was inhibited by 40-50% in animals not treated with radioprotectants as compared to control. Balanced high pools of dNTPs in the organs of radioprotectant-treated animals provided for high-performance repair of DNA damage. The radioprotectant-induced activation of dNTP synthesis during the development of compensatory and restorative responses provides for an earlier restoration of the cellular composition and functioning of the organs. Antioxidants stimulated the synthesis of dNTPs, DNA, and proteins in animal tissues in a strict dose interval. Their effect on the studied syntheses was dose-dependent: single or multiple long-term administration of high antioxidant doses inhibited synthesis of dNTPs, DNA, and proteins. Radioprotectants and antioxidants affected the pool of blood protein Fe3+-transferrin controlling the synthesis of iron-containing ribonucleotide reductase activity in hematopoietic organs, and hence, the iron-dependent stage in DNA synthesis--dNTP synthesis. Activation of protein synthesis in organs by the studied substances increased the pools of Fe3+-transferrin and Cu2+-ceruloplasmin in the blood, which activated dNTP and DNA synthesis. Activated synthesis of dNTP, DNA, and proteins in the organs and increased pools of studied plasma proteins underlay the formation of body resistance to DNA-damaging factors.

[Anabolic effect of natural and synthetic antioxidants]. / Anabolicheskii éffekt prirodnykh i sinteticheskikh antioksidantov.

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. The changes in these parameters had a phase mode with maxima on days 2-3 and 6-8. The stimulatory effect of the antioxidant on the processes of synthesis was concentration-dependent. We found that the optimal stimulation of the synthesis of deoxyribonucleotides, DNA, and protein was achieved by single administration of alpha-tocopherol at a dose of 20 mg per dog with an average weight of 15 kg and 17 mg/kg in the case of mice. Single or repetitive administration of higher doses of alpha-tocopherol was either ineffective or even suppressed the synthesis of DNA and deoxyribonucleotides. Ionol administered at a dose of 60 mg/kg increased DNA and protein synthesis in mouse organs in 2-4 and 1.2-1.5 times, respectively, compared to the control. It was also shown that single and repetitive administration of alpha-tocopherol to dogs increased the pool of Fe3+ -transferrin and Cu2+ -ceruloplasmin in blood in 2-3 times and by 20-30%, respectively, compared to the control. It is suggested that changes in Fe3+ -transferrin pool in peripheral blood may be used for evaluation of the stimulatory effect of antioxidants on the synthesis of macromolecules in organs and for the determination of dependence of this effect on the concentration of antioxidants.

[Reactions of deoxyribonucleotide synthesis system to irradiation and their modification by radioprotectors]. / Reaktsii sistemy sinteza dezoksiribonukleotidov na obluchenie i ikh modifikatsiia radioprotektorami.

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. It has been shown that organism defence mechanisms against irradiation include the following stages: 1. The prompt SOS-activation of dNTP synthesis 30 min later after irradiation, playing the important role in protecting of cell's genetic apparatus from damage. 2. The inhibition of dNTP synthesis within 3-24 h after irradiation resulting to the imbalance of four dNTP and the decrease of their pools. As result of that, the abnormal repair is observed due to depurinations, errors of base incorporations and "misrepair". 3. The restore of dNTP synthesis occurred 2 days later after irradiation. The increase of dNTP pools promotes the increase of DNA synthesis rate as well as proliferative activity of cells. Confirming the fact that the alterations in dNTP pools play essential role in the production of DNA lesions became an important step in understanding of the multistage process leading to radioprotection. To get high and balanced pools of dNTP needed for the increase in the volume of repair of DNA lesions the radioprotectors with high efficiency relative to the survival test were used in experiments. They induced the elevated dNTP synthesis in bone marrow and spleen during the time when the irradiation alone caused the essential prolonged suppression of dNTP synthesis as well as DNA and protein synthesis in organs of nonprotected animals. It has been shown that substances with antioxidant and antiradical activity induced the dNTP synthesis, too. In vivo regulatory factors of dNTP synthesis have been studied to elucidate the mechanisms of getting of high and balanced dNTP pools by using of different substances.

[Reaction of rats organ cells to inhibition of protein biosynthesis by sublethal doses of cycloheximide]. / Reaktsii kletok organov krys na ingibirovanie biosinteza belka tsiklogeksimidom v subletal'noi doze.

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. In response to these metabolic disturbances, nonspecific compensatory recovery reactions developed, first of all, the "reprograming" of the translation process to produce new protein-synthesizing elements instead of cycloheximide-blocked ones. The activation of protein synthesis promotes the recovery of deoxyribonucleotide and DNA synthesis, the restoration of the redox state of mitochondrial and microsomal electron transport chains in organs as well as an increase of Fe(3+)-transferrin and Cu(2+)-ceruloplasmin pools in rat blood. These metabolic processes result in the full recovery of the functional ability of organs.

[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]. / Vremennye i dozozavisimye postradiatsionnye izmeneniia v soderzhanii Fe3+-transferrina i Cu2+ tseruloplazmina v krovi zhivotnykh i ikh vliianie na ribonukleotidreduktaznuiu aktivnost' tkanei.

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. This irontransport protein controls a rate-limiting iron-dependent stage for DNA synthesis--the synthesis of dNTP, catalyzed by iron-containing ribonucleotide reductase (Fe(3+)-RR). It has been shown that time-dependent post-irradiation changes of Fe(3+)-TP pool in blood are characterized by three distinct stages: 1) the prompt increase of pool (SOS-type response) playing the important role in protecting of cell's genetic apparatus from damage; 2) the decrease of its pool within 3-18 h after irradiation resulting in the loss of Fe(3+)-RR activity in tissues of blood-forming organs that make more stronger radiation-induced damage; 3) the following phase-dependent increase in Fe(3+)-TF pool at the 2-nd, 6th, 10-17th days after irradiation due to an increase in transferrin synthesis. This increase may be considered as compensatory reaction of blood-forming organs directed at restoring blood and organ's cells. The time-dependent courses of the reactions are independent from radiation doses indicating to the universal and nonspecific response of organism against irradiation. But, the intensity of this compensatory-adaptive response at 2-nd and 6th days grows with increasing radiation dose up to lethal that, and organism's response becomes abnormal and physiologically hypertrophic. The prolonged "stressful syndrome of biochemical tense state" should be attributed to negative effects for organism, since it may result in the failure of compensatory adaptive organism's reactions and animal killing. The radioprotectors ward off the appearance of this dangerous state. Dogs with initial individual characteristics of blood which were typical for "suppressed" or "activated" states had abnormal response against irradiation by low doses 0.25 or 0.5 Gy. In these cases the intensity of response reactions of organism was essentially increased and markedly deviated from linear dose dependence. The phase-dependent increase of Fe(3+)-TF pool in blood in post-irradiation time resulted to the increase of Fe(3+)-RR activity in blood-forming organs. The key event ensuring the development of compensatory adaptive reactions is the increase of capacity of protein-synthesizing apparatus, the activation of biosynthesis of dNTP and DNA against the treatment with damaging factors.

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. The results obtained show that the rapid and transient increase in NDPR activity in animal organs occurs as cellular response against the treatment with DNA-damaging agents (SOS-type activation). We have also found the intensive radioprotector-stimulated activation of deoxyribonucleotide synthesis as well as DNA and protein synthesis in mice organs within 3 days after the administration of two radioprotectors, indralin and indometaphen, that provide the high animal survival. Our studies suggest that these effects are the most important steps in the protective mechanism of the radioprotectors and are responsible for the high animal survival.

[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]. / Gribkovaia infektsiia organov cheloveka rezistentnymi melaninsinteziruiushchimi vidami iavliaetsia odnim iz patogennykh faktorov i real'nykh posledstvii avarii na ChAES.

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., Candida albicans) as well as the melanin, extracted from fungal conidium. It has been shown that the melanin centers found in BAL cells of liquidators is the melanin of melanin-synthesizing mutant fungi Aspergillus fumigatus and Aspergillus flavus. The prolonged gamma-irradiation at low dose rate and the effects of inhaled radioactive particles cause the adaptive mutation of micromycetes producing the chemo- and radioresistant population. We think that the radioactive dust and pathogenic mutant micromycetes were inhaled in lungs of liquidators during their work at the Chernobyl NPP. Thus, one of valid consequences of Chernobyl accident may be the wide fungous of human organs, in particularly, by Aspergillus mutant. The radiation-induced weakening of immune reactions of liquidators promotes the resistance of this fungus mutant infection.

[The molecular mechanisms of the action of the radioprotector indometafen. The biosynthetic and bioenergetic aspects]. / Molekuliarnye mekhanizmy deistviia radioprotektora indometafena. Biosinteticheskie i bioénergeticheskie aspekty.

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. At later stages (2-20 days) IM activates protein and DNA synthesis leading to the recovery of the ribonucleotide reductase activity in the spleen, on increased content of Fe3(+)-transferrin, cytochrome-c-oxidase, and ferrosulfuric components of the mitochondrial electron transport chain, and increased potential of the detoxication system due to the elevated content of cytochrome P-450. IM stimulates ATP synthesis. Thus, IM enhances compensatory-restorative reactions of the cell systems, more pronounced in the spleen than in the liver.

[Markers of the metabolic changes arising as a result of ionizing radiation exposure]. / Markery metabolicheskikh izmenenii, voznikaiushchikh vsledstvie vozdeistviia ioniziruiushchei radiatsii.

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. The causes of these changes and the possibility for these indices to be used in estimating leucosis risk are discussed. Radiation-induced increases in RR activity are discussed in relation to the SOS-response to DNA damage; an increased pool of deoxyribonucleotides is necessary for repair of DNA. The mean contents of extracellular DNA, TF and CP in the blood plasma were obtained from children of different ages degrees of radioactive contamination suffering the consequences of the accident at the Chernobyl' Nuclear Power Station (n = 155). Groups of children have been isolated with increased, sharply decreased, and close to normal levels of extracellular DNA, TF, and CP. The lowered TF pool was observed in children with thyroid glands damaged by incorporated radioactive iodine with the degree of suppression determined by the dose. For most children subject to general irradiation, the TF and CP pools in the blood were higher than in the control, suggesting an adaptive response to irradiation.

[Rapid metabolic changes in the blood and organs of rats under the influence of electron pulse radiation at superhigh doses]. / Bystrye metabolicheskie izmeneniia v krovi i organakh krys pod vliianiem impul'snogo izlucheniia élektronov v sverkhvysokikh dozakh.

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. Antioxidative activity of lipids in various tissues differed in the rats with "the early loss of performance" syndrome and in normal rats. Possibility of ammonia intoxication of the brain soon after irradiation at superlethal doses has been discussed.

[The molecular aspects of the action of the radioprotector indralin]. / Molekuliarnye aspekty deistviia radioprotektora indralina.

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. Indralin has induced marked favorable changes in the rate of macromolecular synthesis, normalized the ATP and glycogen content, induced ribonucleotide reductase activity and increased the Fe(3+)-transferrin content during development of compensatory-repair response in the irradiated animals. Indralin prevented hyperdevelopment of the repair response and its breakdown due to radiation-induced exhaustion of viability of many important cellular and body systems after irradiation with lethal doses.