[The role of cyclic nucleotides in the processes of adaptation and alteration of body radiosensitivity]. / Rol' tsiklicheskikh nukleotidov v protsessakh adaptatsii i izmenenii radiochuvstvitel'nosti organizma.

The experimental data on the role of the cyclic nucleotides (cAMP, cGMP) in the mammalian integrating systems and their significance in the processes of adaptation and radiosensitivity change of animals are analysed. The changes in the system of cyclic nucleotides (CN) are reported for a number of morbid conditions at the subunit level. The CN system changes as a body response to the extreme action including ionizing radiation are revealed. A concept on a phase correlation between adrenergic and cholinergic system activity in development of adaptive reaction of a cell and a body on the whole during radiation or the action of some other factors is emphasized. The significance of cAMP/cGMP ratio calculation (coefficient K) is underlined for the analysis and prediction of the morbid state outcome.

[Changes in metabolism of the nervous system in exposure to ionizing radiation at supralethal doses]. / Izmeneniia metabolizma nervnoi sistemy pri deistvii ioniziruiushchei radiatsii v sverkhletal'nykh dozakh.

Some biochemical disorders in the animals' central nervous system mainly in brain have been analysed after the exposure to superlethal doses of ionizing radiation as well in a state of the so-called early transient incapacity. The metabolism of gamma-aminobutyric acid, ammonia, histamine, cyclic nucleotides, prostaglandins and other biologically active substances is compared. Their investigation as metabolic regulators and modulators for nerve tissue seems to be of particular importance for deciphering the molecular mechanisms of changes in the central nervous system functional state and for discovering the possibility of its maintaining at a given level of activity.

[Biochemical reception and ionizing irradiation of the body]. / Biokhimicheskaia retseptsiia i ioniziruiushchee obluchenie organizma.

The authors present the idea of the importance of studying the mechanism of biochemical reception of biologically active compounds (BAC) particularly the reception of prostaglandins after the effect of ionizing radiation on eucaryotes as a factor playing a significant role in understanding the radiation sickness pathogenesis. The perspectives of studying BAC reception are prognosticated for searching new radiomodifying agents (radioprotectors and means for treating radiation sickness).

[Prostaglandins and interphase death of irradiated cells]. / Prostaglandiny i interfaznaia gibel' obluchennykh kletok.

The contribution of the post-irradiation changes in prostaglandin transformation to the biochemical mechanism of interphase death of irradiated cells is estimated. It is supposed that prostaglandins are secondary trigger-effectors which initiate the development of primary biochemical reactions giving rise to radiation sickness. It is suggested that the biochemical mechanism of interphase death is complex and involves several concurrent trigger mechanisms including prostaglandin regulation system.

[UMP synthase activity of rat tissue extracts in the bone marrow form of radiation sickness]. / Aktivnost' UMF-sintazy v ékstraktakh tkanei krys pri kostnomozgovoi forme luchevoi bolezni.

Whole-body gamma-irradiation of rats with a dose inducing bone marrow radiation syndrome caused phase organospecific changes in UMP-synthase activity. Disturbances of enzymic activity in the bone marrow and spleen well correlated with the dynamics of interphase and reproductive cell death. In brain extracts, UMP biosynthesis from orotic acid did not undergo essential changes.

[Postradiation disorders in the adenine-phosphoribosyltransferase pathway of AMP biosynthesis]. / Postradiatsionnye narusheniia adenin-fosforiboziltransferaznogo puti biosinteza AMF.

A study was made of the activity of adenine-phosphoribosyltransferase (EC 2.4.2.7), which catalizes the biosynthesis of AMP from adenine and 5-phospho-alpha-D-riboso-1-diphosphate, in extracts from thymus and liver during 24 h following irradiation of mice in a dose of 245.1 mC/kg (dose-rate of 9.16 X 10(-4)-9.0 X 10(-4) A/kg). Adenine-phosphoribosyltransferase activity of liver remains normal during the entire period of observation. In thymus extracts, the activity of the enzyme decreases down to 70-80% of the control level 3 h after irradiation, it is normalized after 6 h and increases up to 150-160% of the control level by the end of the first day of radiation sickness.

[Molecular mechanisms of radiation death of lymphoid cells. Chromatin degradation and DNA replication in fractions of irradiated thymocytes]. / Issledovanie molekuliarnykh mekhanizmov radiatsionnoi gibeli limfoidnykh kletok. Degradatsiia khromatina i replikatsiia DNK vo fraktsiiakh obluchennykh timotssitov.

Chromatin of irradiated large and small thymocytes starts degrading 2 h following irradiation. However the yield of polydeoxynucleotides is more intensive in small thymocytes which are more radiosensitive. Immediately after irradiation small thymocytes exhibit activation of impulse incorporation of 3H-thymidine into a DNA fraction which does not exceed half the replicon by its molecular mass.

[Study of the nature of increased weight of lymphocyte superhelical DNA during cell incubation in vitro]. / Issledovanie prirody "utiazheleniia" superspiral'noi DNK limfotsitov v protsesse inkubatsii kletok in vitro.

The nature of the increased sedimentation of superhelical DNA (sDNA) during incubation of both intact and irradiated thymocytes has been studied. The "weighting" of sDNA was not consequent on the changes in superhelical density. No quantitative or qualitative changes in the composition of proteins connected with sDNA in the course of its "weighting" were found either. It is assumed that sDNA "weighting" seen during incubation of the cells exposed to non-physiological factors (irradiation, hyperthermia, incubation in a poor medium) reflects the processes of chromatin condensation followed by the apoptic death of lymphoid cells.

[Molecular mechanisms of radiation death of lymphoid cells. Protein poly-ADP-ribosylation in thymocyte fractions]. / Issledovanie molekuliarnykh mekhanizmov radiatsionnoi gibeli limfoidnykh kletok. Poli-ADF-ribozilirovanie belkov vo fraktsiiakh timotsitov.

A study was made of the process of poly-ADP-ribosylation of proteins in cells of radioresistant and radiosensitive fractions of mouse thymus lymphocytes after irradiation of isolated cells with a dose of 25 Gy. It was shown that activation of ADP-ribosylation of proteins occurred simultaneously with the formation of single-strand DNA breaks in thymocytes, and the degree of activation in radioresistant and radiosensitive fractions was nearly the same.

[Molecular mechanisms of radiation death of lymphoid cells. Radioprotective effect of cysteamine on a subpopulation of thymocytes differing in radiation sensitivity]. / Issledovanie molekuliarnykh mekhanizmov radiatsionnoi gibeli limfoidnykh kletok. Radiozashchitnoe deistvie tsisteamina na subpopuliatsii timotsitov, razlichaiushchiesia po radiochuvstvitel'nosti.

The radioprotective effect of cysteamine, incubated with thymocytes for 20 min prior to gamma-irradiation, was much more manifest with regard to subpopulations of radiosensitive small cortical cells (DMF = 1.8) than large thymocytes (DMF = 1.2). Radioprotective concentrations of cysteamine relaxed completely superhelical DNA of thymocytes. The relaxation was not due to the formation of single-strand breaks. A partial recovery of superhelical conformation of DNA of small thymocytes before irradiation reduced the radioprotective effect of cysteamine.

[Nature of conformational restrictions in nuclear superhelical DNA from thymus lymphocytes]. / Priroda konformatsionnykh ogranichenii v iadernoi superspiral'noi DNK limfotsitov timusa.

The lymphocyte nucleoids of mouse thymus contain about 40% of rapidly labelled nuclear RNA, about 9% of total intracellular protein and all nuclear DNA. Relaxation of superhelical DNA after thymocyte nucleoids treatment with pronase or RNAase suggests that non-histone proteins and/or RNAs are involved in conformational restrictions in the superhelical domains of cell DNAs. Thymocyte nucleoids proteins are represented by two groups of nonhistone proteins with molecular weights of 50 000-60 000 and 75 000-85 000. An essential role in the appearance of conformational restrictions in thymocyte superhelical DNA belongs to disulfide bonds.

[Action of modifiers of a radiation lesion on the binding of prostaglandin E2 with liver membranes in F1 CBA X C57BL strain mice]. / Deistvie modifikatorov luchevogo porazheniia na sviazyvanie prostaglandina E2 s membranami pecheni myshei linii F1 CBA X C57BL.

Prostaglandin E2 (PGE2) was specifically bound by the membrane fraction prepared from the mouse liver. The binding constants indicate the presence of high-affinity PGE2 binding sites with an apparent dissociation constant (Kd) of 0.82 X 10(-9) M and a capacity of 0.36 X 10(9) M/mg protein and a lower affinity PGE2 binding site with Kd = 15.73 X 10(-9) M and a capacity of 5.31 X 10(9) M/mg protein. The radioprotectors, MEA and APAETP inhibit PGE2 binding and alter its kinetics. Apparently the mechanism of PGE2 binding by membranes is related to interaction of prostaglandins with thiols and sufhydryl groups of membrane lipoproteins, while the radioprotectors modify the functional groups participating in receptor PGE2 binding.

[Cyclic nucleotides (cAMP and cGMP) in the dog plasma during extracorporeal hemocarboperfusion]. / Tsiklicheskie nukleotidy (tsAMF i tsGMF) v plazme krovi sobak pri ékstracorporal'noi gemokarboperfuzii.

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.

[Interaction of beta-mercaptoethylamine with the enzymatic system responsible for the biosynthesis of prostaglandins E2 and F2 alpha]. / Vzaimodeistvie beta-merkaptoétilamina s fermentnoi sistemoi, uchastvuiushchei v biosinteze prostaglandinov E2 i F2 alpha.

After intraperitoneal administration of beta-mercaptoethylamine (MEA) into mice of F1 strain (CBA XC57B1) at a radioprotective dose, activity of PGE2 and PGF2 alpha-synthetases was decreased in liver microsomes, testicular and brain supernatants (16,000xg) within 15 min, which corresponded to period of the highest radioprotector activity. Amount of newly synthesized prostaglandins was increased in liver tissue within the subsequent periods. Within 3 hrs after the radioprotector administration these amounts constituted for PGE2 246% and for PGF2 alpha 262% as compared with controls; at the same time, activity of PG-synthetases in testes was normalized. In the brain tissue within 1 hr the newly synthesized prostaglandins amounted to 121% for PGE2 and 125% for PGF2 alpha, within 3 hrs they decreased to control values. Decrease in activity of PGE2 and PGF2 alpha-synthetases was shown to depend on MEA concentration in vitro. Possible mechanisms of the radioprotector effect at various steps of the prostaglandins biosynthesis are discussed.