[Effect of synthetic tripeptides on hemopoietic stem cells in norm and after gamma-irradiation].

Our work was aimed at researching into the influence of dipeptide (gamma-dGlu-dTrp) "Timodepressin" and this dipeptide-based tripeptides on the colony-forming ability of the irradiated in vitro bone marrow and hemopoietic stem cells of the normal organism. Also studied was the effect of various doses (1-1000 microg/kg) of one oftripeptides (dAla-gammadGlu-dTrp) on the output of exogenous splenic colonies in the case of its introduction 48 hours before irradiation. It is shown that the mode of influence of the preparations produced on the basis ofdipeptides dGlu-dTrp and gamma-dGlu-dTrp on the initial stages ofa hemopoiesis in the normal and irradiated organism depends on the nature of the additional amino-acid residue and its optical orientation.

[Experimental assessment of embryotoxic action of low intensity ionizing irradiation in different periods of intrauterine development].

The prolonged ionizing radiation exposure at the absorbed doze rate of 2.6 mGy/hour and the total accumulated doze of about 20 cGy during different periods of the intrauterine development caused disorders of a coordinated development of organs and the decrease of endurance in physical activity in the postnatal ontogenesis of the irradiated posterity. The results obtained are comparable to the consequences of irradiation exposure of the fetus at the accumulated doze of 125 cGy during all stages of pregnancy and give grounds for considering radiation exposure at the above-mentioned rate (20 cGy) as a biologically significant factor.

[Influence of peptide derivatives of diketopiperazines on hemopoietic stem cells of an intact organism and irradiated bone marrow cells in vitro].

We have performed structural and functional studies of the hemotropic activity for a number of novel 2,5-diketopiperazine peptidomimetic derivatives. We employed a mouse model of hemopoietic stem cells cloning in the spleen of lethally irradiated animals. Biologic activity of synthetic products was studied in two experimental models: 1) in vitro irradiated bone marrow SFU-S was used for studying the radio modifying activity; 2) the biological effect of peptidomimetics on the intact non-irradiated bone marrow was evaluated in vivo. Various ways of administration of the peptidomimetics studied were used in the in vivo experiments: intravenous, intraperitoneal or subcutaneous injections and oral administration in the dose range of 10-10000 microg/kg. As a result of our work, we have discovered 2,5-diketopiperazine peptidomimetic derivatives with the dual activity: stimulation of intact committed SFU-S and radiomodifying activity.

[Experimental study of the radioprotective action of melanin on the somatic development during irradiation in the antenatal period of ontogenesis].

Daily introduction per os of the exogenous melanin in a doze of weight of 10 mg/kg pregnant female rats Wistar eliminated the functional deficiency of somatic development revealed at posterity at chronic gamma-irradiation in a doze 1.00-1.25 Gy for all period of pregnancy. The irradiation or introduction melanin antenatal to a phase ontogenesis resulted in stimulation of the immune answer, which was determined at offspring on 3rd week after birth. On the basis of the received data it is concluded presence radioembryoprotective actions melanin in the relation embryotoxic effects of small dozes of ionizing radiation and its participation in regulation immunogenes.

[Experimental study of the neuroprotective properties of the melanin in embryos irradiated during antenatal development].

Daily introduction per os of the exogenous melanin in a doze of weight of 10 mg/kg pregnant female rats of line Wistar on a background continuous irradiations (dose rate of 2.6 mGy/h within 20 days of pregnancy) eliminated deficiency cognitive functions at posterity. On the basis of the received data it is concluded presence radioembryoprotective actions of melanin in the relation neuro embryotoxic effects of small dozes ionizing radiation. Taking into account small toxicity of melanin, the preparation can be perspective for practical application.

[The efficiency and direction of thymus changes after whole-body exposure of mice to the weak electromagnetic field are determined by the initial status of the thymus]. / Iskhodnoe sostoianie timusa opredeliaet kharakter izmenenii v organe u myshei pod vozdeistviem slabykh élektromagnitnykh doz.

The work presents results of the experimental study on thymus changes developing after whole-body exposure of mice to ultralow power pulse-modulated electromagnetic field (carrying frequency 2.39 GHz, modulating pulses with frequency 4 Hz, duration of impulses 0.025 sec, average power density 60 mW/cm2, absorbed dose 0.086 J/g or 0.172 J/g). It was shown that a percent of the microwave induced increase or decrease of thymus mass and the number of cells in the organ (y) are determined by the initial mass or number of cells in thymus accordingly to equation of linear regression: (yx = 215-2.25x, where x is the thymus mass of control animals (in a range 31-63 mg) and (yx = 178.6-41x, where x is the initial number of cells in thymus (in a range 0.6 x 10(8)-2.6 x 10(8)) reduced by a factor of 10(8).

[Dependence of microwave effect on the secondary structure of DNA on molecular weight of polynucleotide]. / Zavisimost' éffekta oslableniia mikrovolnami vtorichnoi struktury DNK ot molekuliarnoi massy polinukleotida,

The effect of ultralow power pulse-modulated electromagnetic radiation (average power density 60 microW/cm2, carrying frequency 1.05; 2.12; or 2.39 GHz; modulating pulses with frequency 4 Hz) on the secondary structure of DNA was investigated. It was established that the exposure of beta-alanine and formaldehyde containing aqueous DNA solution to electromagnetic radiation had activated the process of DNA despiralization under the action of beta-alanine--formaldehyde reaction product. The effect of electromagnetic radiation on the secondary structure of DNA can be removed by lowering of molecular weight of DNA to 0.46 x 10(6) (at carrying frequency 1.05 GHz), or to 0.25 x 10(3) (at carrying frequency 2.39 GHz).

[Physicochemical study of the state of protein and lipid phases in synaptosome membranes following irradiation with fast electrons]. / Fiziko-khimicheskoe issledovanie sostoianiia belkovoi i lipidnoi faz v membranakh sinaptosom posle oblucheniia bystrymi élektronami.

No activation of lipid peroxidation and structural rearrangements were noted in the lipid phase of synaptosome membranes after exposure of animals to electrons of 300 Gy/min at doses inducing cerebral lesions. At the same time, in isolated synaptosome membranes, radiation induced defined changes manifested by a decrease in tryptophan fluorescence.

[Brain beta-adrenergic and GABA-ergic receptors in rats after exposure to high doses of ionizing radiation]. / Sostoianie beta-adrenergicheskikh i GAMK-ergicheskikh retseptorov mozga krys posle vozdeistviia vysokikh doz ioniziruiushchei radiatsii.

The radioactive ligands, [3H]dihydroalprenolol and [3H]muscimol, were used to estimate the condition of beta-adrenoreceptors of the brain cortex and GABA-receptors of the cerebellum during transient neurologic disorders caused by irradiation of rats with high-energy (20 MeV) electrons of 200 Gy. No significant changes were observed in the GABA-ergic brain system while the changes in beta-adrenoreceptors of the brain were pronounced and manifested by the loss by the receptors of their ability to bind the specific ligand, dihydroalprenolol. The changes observed were reversible and correlated with the development of neurologic disorders.

[Toxic and radiosensitizing effect of reduced nitroimidazoles on E. coli B/r cells]. / Toksicheskoe i radiosensibiliziruiushchee deistvie vosstanovlennykh nitroimidazolov na kletki E. coli B/r.

The spectrophotometric method was used to study the rate of chemical reduction of misonidazole and metronidazole by NH4Cl and Zn in the atmosphere of argon and oxygen. Reduction of drugs increased their toxicity for hypoxic and oxygenated E. coli B/r. The reduced metronidazole is a more effective radiosensitizer of hypoxic E. coli B/r than the original compound.

[Effects on the process of DNA transcription in vitro of formaldehyde and the products of its reaction with amines]. / Vliianie na protsessy transkriptsii DNK in vitro formal'degida i produktov ego vzaimodeistviia s aminami.

When transcription of DNA treated with aminomethylol compounds (products of formaldehyde reaction with amines) was studied, aminomethylol produced a marked inhibition of the template activity of double-stranded DNA (up to 85%). Formaldehyde suppressed the transcription of native DNA as well, however, only when taken at concentrations exceeding those of the aminomethylol compounds 20-fold.

[Modification of guanine residues in double-stranded DNA by aminomethylol compounds without denaturation of nucleic acid]. / Modifikatsiia ostatkov guanina v dvuspiral'noi DNK aminometilol'nymi soedineniiami, ne soprovozhdaiushchaiasia denaturatsiei nukleinovoi kisloty.

With the application of radioactive formaldehyde and glycine the ability of aminomethylol compounds to combine with S1 nuclease treated DNA at 25 degrees and pH 5.8--7.4 has been shown. The reaction leads to modification of 22--26% of base pairs without changes of the DNA UV-absorption spectrum. Besides that the flexibility coefficient, the kinetics of despiralization under the action of formaldehyde and the stability of DNA molecule towards the S1 nuclease action permit to conclude that modification does not cause DNA despiralization. In experiments with the use of synthetic double-stranded polynucleotides poly(dA) times poly(dT), poly(rC) times poly(rl), poly(rG) times poly(dC) and poly(dC-dG) times poly(dC-dG) it has been shown that binding of methylol compounds to nucleic acids is due to reaction with guanine residues. Methylol derivatives of glycine reacts with guanine residues of double-stranded DNA only 10 times slower than with the monomer--deoxyguanosine-5'-phosphate. The studied reaction is reversible and the half-period of modified DNA reduction is found to be 5 hours at 25 degrees and pH 6.5. The rate constants of forward and reverse reactions and equilibrium constants of the reaction between methylolglycine and native DNA were determined.

[Interaction of monomeric components of nucleic acids with histone and polylysine in the presence of formaldehyde]. / Vzaimodeistvie monomernykh komponentov nukleinovykh kislot s gistonom i polilizinom v prisutstvii formal'degida.

The ability of various nucleosides and nucleotides to bind to histone and polylysin upon formaldehyde treatment was investigated. It was shown that in protein or polypeptide preparations the guanine derivatives are present in much greater amounts than other nucleic base derivatives. No synthesis of stable products was observed thereby. It was assumed that the formation of the DNA - histone complex upon nuclear histone treatment with formaldehyde depends on the formaldehyde-induced reaction between the histone and guanine bases of DNA.

[Kinetics of the reaction between formaldehyde and proteins]. / Kineticheskoe issledovanie vzaimodeistviia formal'degida s belkami.

The reaction between formaldehyde and protein has been studied with the use of a radioactive indicator. In the presence of excess formaldehyde the reaction is kinetically of the first order. The accordance of experimental results to the kinetic scheme of a biphasic process was shown. On this basis experimental and veritable rate constants, equilibrium constants of mono- and dimetilol derivatives formation, the energy of activation and pseudothermodynamic parameters were determined. The dependence of reaction rate and degree of protein modification from formaldehyde concentration and temperature are discussed. Given results permit to optimize and control the process of interaction between formaldehyde and proteins.

[Effect of formaldehyde and its aminomethylol derivatives on E. coli strains with various defects of the DNA repair systems]. / Vozdeistvie formal'degida i ego aminometilol'nykh proizvodnykh na shtammy E. coli s razlichnymi defektami repariruiushchikh sistem DNK.

It was shown that aminomethylol compounds formed during reaction of formaldehyde with amino acids and formaldehyde as well exert a pronounced lethal action on E. coli strains with various defects of the DNA repair systems. The correlation between the extent of the DNA depurination caused by in vitro action of diverse aminomethylol derivatives and the inactivation of bacteria by these derivatives is revealed. The data obtained suggest that the inactivating effect of formaldehyde and its aminomethylol derivatives seems likely to be due to the formation of depurinized groups in bacterial DNA rather than to dimerization of purine bases.

[The action of products of the formaldehyde reaction with different amines on nucleic acids and their components]. / Deistvie produktov reaktsii formal'degida s razlichnymi aminami na nukleinovye kisloty i ikh komponenty.

The kinetics and equilibrium of the reaction between nucleic acids components and the products of formaldehyde interaction with ethanolamine and different amino acids has been studied. These parameters were found to be similar for all the products used. The destabilization of the N-glycosidic bond in deoxyadenosine caused by formaldehyde derivatives of different amines was studied. The rate of the cleavage of the N-glycosidic bond under the action of formaldehyde derivatives of glycine and ethanolamine was found to be 10 times greater than that under the action of formaldehyde derivatives of other amines. It is shown that DNA preparations with different content of adenine can be obtained by adding the product of formaldehyde reaction with glycine to DNA.

[Use of the reaction product of beta-alanine and formaldehyde in the kinetic method of determining defects in secondary structure]. / Ispol'zovanie produkta vzaimodeistviia beta-alanina s formal'degidom v kineticheskom metode opredeleniia defektov vtorichnoi struktury DNK.

It is shown that the kinetics of DNA despiralization in the presence of beta-alanine--formaldehyde reaction product (beta-ALA-FORM) can be described in terms of theory of DNA despiralisation by "slowly reacting agents". Conditions are determined in which beta-ALA-FORM product can be used to establish the concentration of defects in DNA secondary structure. Possible advantages are discussed of using the new agent in the kinetic method of determining DNA defects as compared to formaldehyde, in particular in analysis of DNA complexes with proteins. The data obtained throw some light on the nature of the interaction between beta-alanine and formaldehyde in slightly acidic solutions and with the excess of aminoacid.