[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. 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 inhibitor of free radical processes decrease of protein biosynthesis in gun short wound tissues and weaken development of the general adaptation syndrome].

The dynamics of total protein biosynthesis and procollagen biosynthesis in skeletal muscle of injury tissues with the antioxidant BHT (dibunol) treatment and with common healing were studied. The obtained date indicate that the AO treatment reduce the rate of biosynthesis both the total proteins and procollagen at the 3th day of healing. Dibunol also considerably reduce the protein biosynthesis in adrenals and brake of corticosteroids biogenesis as measured by ESR-signals intensity of reduced adrenodoxine.

[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.

[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.

[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.

[Ecdysterone modulates antitumor activity of cytostatics and biosynthesis of macromolecules in tumor-bearing animals].

The influence of therapeutic and half doses of cisplatin and adriamicin combination with the anabolic drug ecdisteron (20-hydroecdison) on development of subcutaneously and intraperitonially transplanted P388 and L1210 leukemia and metastasizing B16 melanoma was studied. Ecdisteron significantly stimulated the chemotherapeutic effect of low doses of the cytostatics: inhibition of tumor growth, mice survival rate, their lifespan, and the antimetastatic activity index were comparable or better than after therapy with high doses of the antitumor drugs. The influence of high and low doses of cisplatin and its low dose in combination with ecdisteron on the dynamics of protein and DNA biosynthesis in the liver, pancreas, thymus, spleen, and adrenals of tumor-bearing mice were also studied.

[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.

[The structural characteristics of the polyribosomes in the rat liver studied by means of a tritium label].

Polyribosomes isolated from the rat liver in a medium with low ionic strength were irradiated by "hot" tritium atoms under conditions providing for the replacement of the hydrogen atoms located at the surface of polyribosomes by tritium. After fractionation of such polyribosomes, the radioactivity of the obtained fractions was measured and their proportions were calculated for the total surface accessible for the tritium atoms (in %), as well as their specific radioactivity. The material loosely associated with the polyribosomes and containing amino acyl-tRNA-synthetases is more radioactive than rRNA and r-proteins, especially concerning their specific radioactivity.

[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.

[Polyribosomes, isolated from rat liver in a low ionic strength medium, capable of autonomic translation in a cell-free system without the addition of cellular fluid].

Polyribosomes isolated from the liver in the presence of 10 mM KCl and purified by centrifugation through 2 M sucrose were shown to incorporate [3H]leucine both into aminoacyl-tRNA and polypeptides in a cell-free system without cell sap. The incorporation of [3H]leucine showed a linear increase within 80-100 min and was then levelled off. The system was sensitive to cycloheximide, puromycin and ethionine and needed ATP, GTP and unlabeled amino acids.

[Dynamics of the biosynthesis of components of the protein synthesizing apparatus of the rat liver at the stage of restoration of translation, inhibited by cycloheximide].

The biosynthesis of proteins, ribosomal RNA and other components of the rat liver protein-synthesizing system during the reparation and subsequent activation of translation inhibited by a sublethal dose cycloheximide (CHI, 3 mg/kg) was studied. It was found that the incorporation of labeled precursors into proteins and ribosomal rRNA isolated from free and membrane-bound polysomes is repaired already 3 hours after CHI injection. 6-9 hours thereafter, the level of component labeling reaches control values, whereas the total protein biosynthesis is retarded.

[Rat liver energetics according to data of 31P-NMR in extreme states of the processes of biosynthesis of proteins and nucleic acids].

The dynamics of phosphomonoesters, phosphodiesters, Pi, ATP, ADP, NAD(H+) and uridine diphosphoglucose (UDPG) levels in rat liver upon sharp oscillations in the rates of protein and nucleic acid biosynthesis induced by a sublethal++ dose of cycloheximide was studied, using the 31P-NMR method. The results obtained with preparations of native liver are unaffected by fractionation, homogenization and chemical extraction procedures. It was demonstrated that oscillations of Pi, ATP and UDPG levels in liver cells reflect the changes in the energy consumption and intracellular energy-linked processes (e.

[Characteristics of [3H]cycloheximide distribution, protein and DNA biosynthesis in rat organs after sublethal blocking of translation].

The kinetics of accumulation and release of [3H]cycloheximide (CHI) as well as protein and DNA biosyntheses in some organs of the rats injected with sublethal doses of CHI were studied. It was shown that in the majority of organs under study (especially in the liver, kidneys and adrenals) the inhibition is completed within 12 hours after CHI injection followed by the resumption of protein and DNA syntheses. In the thymus and pancreas the levels of these biosyntheses remain below control values up to the 72nd hour.

[The 31P-NMR study of the metabolism of phosphate-containing compounds in the rat liver during inhibition of protein synthesis].

Using the 31P-NMR method, the composition of the pool of phosphate-containing metabolites in intact rat liver 72 hours following the blocking of protein biosynthesis by cycloheximide was studied. It was shown that during maximal inhibition, i.e.

[The effect of gamma-hydroxybutyric acid on the biosynthesis of macromolecules and metabolic paramagnetic centers in hepatocytes in acute radiation injury].

It has been shown, that the single injection of gamma-hydroxybutyric acid (GHBA) (100 mg/kg) to mice 30 min before irradiation (6 Gy) prevents whole-body irradiation-induced inhibition of DNA at early post-irradiation period. GHBA stimulates the biosynthesis of macromolecules at 1-2 days after irradiation. GHBA also prevents the increase in the degree of reduction of the mitochondrial and microsomal electron transport chains at early post-irradiation time (up to 2 h.

[Radiation-induced free radicals in DNA, DNA level in tissues and tissue radiosensitivity].

Radiochemical yields (G-values) of H-adducts of thymine bases of DNA (TH) in frozen (77 K) gamma-irradiated mouse and rat tissues were measured. The content of DNA and the number of TH radicals formed in DNA mass of 10(12)D at a dose of 1 Gy (beta parameter) were determined for each of the studied tissue. It was shown that beta parameter, which indicated DNA in situ radiosensitivity, was different for different tissues: it was higher for radiosensitive tissues.

[Activation of nuclear polypeptide synthesis in rat liver cells after inhibition of template protein synthesis. The role of nuclear polypeptide synthesis in the changes of the chromatin structure].

The correlation between the rates of nuclear polypeptide synthesis (NPS) and matrix protein synthesis in rat liver cells was investigated. It was shown that NPS is activated under conditions of protein synthesis inhibition in the cytoplasm. Model experiments revealed that the NPS and ADP ribosylation systems compete for chromatin structure: ADP ribosylation induces condensation, while NPS--decondensation of chromatin.

[Dynamics of energy requirements, detoxication and biosynthesis of hepatocyte macromolecules in acute radiation injury].

The functional state of the mitochondrial electron transport chain and of hydroxylation system of endoplasmic reticulum and biosynthesis of macromolecules in hepatocytes were studied during acute radiation decrease induced by whole-body gamma-irradiation of mice with doses of 6 and 8 Gy. An increase in the degree of reduction of the mitochondrial electron transport chain at early post-irradiation time (up to 2 h) was demonstrated by the ESR method. At the same time stimulation of transcription and marked inhibition of rates of protein and DNA biosyntheses were noted.

[Complex nature of the inhibitory effect of the cytosol on transcription in isolated nuclei of rat liver].

It was shown that rat liver cytosol contains a factor inhibiting [3H]UTP incorporation into RNA of isolated nuclei. Fractionation of cytosol by Sephadex G-100 chromatography, step-wise increase in ammonium sulfate concentration and electrophoresis in polyacrylamide gel revealed a complex nature of cytosol inhibitory activity. It was suggested that this complex nature can be due to the presence of either non-specific inhibitors of transcription (i.

[RNA biosynthesis in mitochondria under conditions of prolonged inhibition of protein biosynthesis in rat liver cytoplasm].

When cytoplasmic protein synthesis is inhibited by cycloheximide (CHI) in vivo synthesis of water-soluble mitochondrial proteins and of mitochondrial RNA is decreased. These changes measured in isolated rat liver mitochondria are similar to those observed in vivo and correlate with the changes the synthesis of water-soluble proteins in mitochondria. When the cytoplasmic fraction (30,000 g-supernatant) had been added to the mitochondria showing decreased RNA synthesis, the RNA synthesis increased to the control level (the incubation conditions were favourable for the protein transport from microsomes to mitochondria).