[Bcl-2 apoptosis regulating proteins in mouse tissues after exposure to 20 cGy of gamma-radiation]. / Belki-reguliatory apoptoza is semeistva bcl2 v tkaniakh myshei posle vozdeistviia gamma-izlucheniia.v doze 20 sGr.

A pronounced increase of Bcl-2 content was observed in thymus of mice exposed to 20 cGy of gamma-radiation 1 and 24 hours after the exposure; six days after the exposure the bcl-2 content lowered to the control one. No changes in bcl-2 level were revealed in mice liver during the period of observation. A level of Bax protein was stable in mice thymus during 60 days of observation.

[The radiation-modifying capacity of xenogenic apotransferrin for the number of endogenous colony forming units in the spleen of irradiated mice]. / Radiomodifitsiruiushchie svoistva ksenogennogo apotransferrina po pokazateliu chisla éndogennykh KOE v selezenke obluchennykh myshei.

After intraperitoneal injection of 100 or 198 mg/kg of human serum apotransferrin (apo TF) to mice 1 day before acute exposure to 6 Gy of gamma-radiation, the number of endogenous CFU in spleen (CFUs) increased 2.5 or 2.6 times respectively. At a dose fo 10 mg/kg of the protein only an increasing tendency was found, whereas a dose of 1 mg/kg was inefficient. A dose of 100 mg/kg of BSA did not show any effect suggesting that non-specific immune response to alien antigen did not contribute to apo TF radiomodifying action. The following mechanisms of the apoTF radiomodifying effect are discussed: 1) the ability of the protein to inactivate Fe3+ ions that reduces the consequences of radiation oxidative stress; 2) the stimulation of proliferation of the exposed bone marrow cells by activation of Fe3+ transport or by Ca2+ mediated mechanism of mitogen signal transduction; 3) changing in the content and ratio of cyclic nucleotides by apo TF stimulation of Ca-calmodulin-dependent phosphodiesterase.

[Parameters of proliferative activity of hematopoietic cells in mice protected from irradiation by indralin in combination with Zn-metallothionein]. / Pokazateli proliferativnoi aktivnosti kletok krovetvornykh organov u myshei, zashchishchennykh ot izlucheniia indralinom v sochetanii s Zn-metallotioneinom.

One day after the irradiation (dose 6 Gy) of mice protected by the injection of Zn-metallothionein (Zn-MT) in doze 8.6 mg/kg, 10-20 min before irradiation, then alpha-adrenomimetic indraline (150 mg/kg) 5-10 min before irradiation the increase in nucleic cell number, [3H] thymidine incorporation, and antioxidant activity in bone marrow in comparison with the control and indraline per se was revealed. In mice protected according to the scheme: Zn-MT in the same doze, then indraline (100 mg/kg) one day after, and then in 5-10 min exposure to 6 Gy it was found more than 9 times increase of endogeneous CFC in spleen on 8th day while indraline per se raised CFC number only 4.8 times. It was found that Zn-MT reduce the indraline acute toxicity. The data on radioprotective activity of monomeric and polymeric Zn-MT forms are submitted.

[The effect of zinc metallothionein on lipid peroxidation in rodent bone marrow cells]. / Vliianie tsink-metallotioneina na perekisnoe okislenie lipidov v kletkkah kostnogo mozga gryzunov.

It was shown, that rat hepatic Zn-metallothionein (Zn-MT) depressed in vitro Fe3+/ADP-induced lipid peroxidation (LP) in rat bone marrow cells and increased its viability after pro-oxidant's influences. ZnCl2 and its combination with cysteine also decreased LP products level, but less and did not alter viability. On 9-th day after gamma-irradiation (6 Gy) in mice protected with Zn-MT the LP products level in bone marrow was decreased in considerable extent.

[The possible mechanism of the antiradiation effect of metallothionein: the stimulation of DNA replicative synthesis and of bone marrow cell proliferation]. / Vozmozhnyi mekhanizm protivoluchevogo éffekta metallotioneina: stimuliatsiia replikativnogo sinteza DNK i proliferatsii kletok kostnogo mozga.

Zn-MT and less apo MT (4-100 mkg/ml) in vitro stimulated the [3H]-thymidine incorporation in mice bone marrow cells, but ZnCl2, its combination with cysteine and mixture (ZnCl2 + cystine + albumin) inhibited DNA synthesis. In protected with Zn-MT (1-4 mg/kg) 10-15 min before irradiation (6 Gy) mice on 9th day after influencing the increasing of DNA replicative synthesis level and nuclear cell number in bone marrow were observed.

[The diverse effects of the combined action of cadmium chloride and ionizing radiation on the content of metallothioneins in mouse bone marrow and liver]. / Razlichnye éffekty sochetannogo deistviia khloristogo kadmiia i ioniziruiushchei radiatsii na soderzhanie metallotioneinov v kostnom mozge i pecheni myshei.

It was shown that introduction of cadmium chloride (0.75 mg/kg Cd2+) in combination with gamma irradiation (8.5 Gy) of mice increases the level of metallothioneines (MTs) in the bone marrow and liver of mice. The maximum effect was observed in 24-30 h after the performance. Similarly, irradiation with the doses of 3 to 10 Gy resulted in an increase in the contents of both MT isoforms (MT1 and MT2) in the bone marrow in 24 h. A combined action of gamma irradiation and a heavy metal caused an additive effect on the MT content in the bone marrow, whereas the MT content in liver was 2 times lower than that predicted theoretically. A possible mechanism of the discovered phenomenon was discussed. Supposedly, it is associated with different degrees of the radiation-induced inhibition of the MT1 and MT2 expression by cadmium ions.

Accumulation of cAMP in gamma-irradiated thymocytes and internucleosomal DNA fragmentation.

Ionizing radiation, glucocorticosteroids and chemical inducers of differentiation (CID) are cytotoxic to thymocytes, and induce internucleosomal DNA fragmentation. Tissue cAMP levels in thymi of irradiated mice were significantly elevated as early as 30 min post-irradiation. In contrast, cAMP content in the liver was not changed significantly up to 1 h post-irradiation, and then some decrease occurred. Irradiation of isolated thymocytes gave essentially the same results as after irradiation of animals, and the elevation in cAMP 30 min after the irradiation, DNA fragmentation and cell death were linearly related to the dose up to 2.5 Gy. The maximal induction of cAMP level occurs in the fractions of radiosensitive cortical thymocytes. In thymocytes all CID tested also induced the increase in cAMP level with concomitant DNA fragmentation. Unlike ionizing radiation, UVC light did not induce cAMP accumulation and DNA fragmentation in thymocytes. Treatment of UV-irradiated cells with But2 cAMP did not result in an increase in DNA fragmentation. Ionizing radiation induced DNA fragmentation and cell death can be prevented by adding the protein kinases inhibitor H-7. Theophylline was shown to reduce the cAMP response, DNA fragmentation and cell death in gamma-irradiated thymocytes, suggesting that the accumulation of cAMP may be partly related to adenosine receptor sites.

Properties of single-stranded DNA-binding proteins (SSB-proteins) from chromatin and nonchromatin fractions of Ehrlich ascites tumour: phosphorylation enhances the affinity of SSB-proteins for single-stranded DNA.

To assess the possible functional role of single-strand DNA-binding (SSB) proteins in eucaryotic cell, a comparative study was made of SSB-proteins isolated from chromatin and the nonchromatin fractions of Ehrlich ascites tumour (EAT) cells. No appreciable differences between the two groups could be found either in SDS-gel electrophoretic patterns or in the ssDNA-binding capacity and stimulation of DNA replication in permeable EAT cells. However, the chromatin SSB-proteins incorporated 1.4-times more labelled phosphate in vivo; phosphate assays in the isolated chromatin and nonchromatin SSB-proteins yielded ca. 3 and 2 moles Pi/mole protein, respectively. Both preparations could be further phosphorylated in vitro with Ca-phospholipid-dependent protein kinase and the catalytic subunit of cAMP-dependent protein kinase, but the non-chromatin proteins were phosphorylated to a greater degree. In parallel with phosphorylation, the SSB-proteins displayed stronger binding to ssDNA cellulose. Phosphorylation may thus be a means of regulating the functions of SSB-proteins, in particular their interaction with chromatin.

[Phosphorylation and other properties of proteins binding single-stranded DNA (SSB-proteins) from chromatin and extrachromatin fractions of Ehrlich ascites carcinoma]. / Fosforilirovanie i drugie svoistva belkov, sviazyvaiushchikhsia s odnonitevoi DNK (SSB-belkov) iz khromatina i vnekhromatinovoi fraktsii kletok astsitnoi kartsinomy Erlikha.

A comparative study of single-stranded DNA-binding proteins (SSB-proteins) isolated from chromatin and the extrachromatin fraction of Ehrlich ascites tumour cells was carried out. No differences were found either in SDS-gel electrophoretic mobility or in the single-stranded DNA-binding capacity and stimulation of the replicative synthesis of DNA. However, chromatin SSB-proteins contained 1.4-1.5 times more phosphate than extrachromatin proteins. Both preparations could be phosphorylated in vitro by protein kinase C and cAMP-dependent protein kinase, but the chromatin proteins were phosphorylated in a lesser degree. In parallel with phosphorylation the SSB-proteins displayed a higher binding affinity for ssDNA-cellulose. Phosphorylation can thus be regarded as a means of regulation of the SSB-protein function, in particular, their interaction with chromatin DNA.

[Effect of agents for the chemical prevention of radiation sickness on the cyclic nucleotide content in the bone marrow of mice]. / Vliianie sredstv khimicheskoi profilaktiki luchevoi bolezni na soderzhanie tsiklicheskikh nukleotidov v kostnom mozge myshei.

The effect of different chemical compounds on the cAMP/cGMP ratio in the bone marrow of mice and radioresistance of animals has been studied. It has been shown that all compounds possessing radioprotective properties give rise to the cAMP/cGMP ratio in the bone marrow of mice. No changes in cAMP and cGMP level were noted after the administration of nonradioprotective substances. The maximal radioprotective effect coincide in time with the largest increase of the cAMP/cGMP ratio. The injection of radioprotectors at different doses demonstrate clearly that only at radioprotective doses the increase in the cAMP/cGMP ratio takes place. The administration of some substances 2, 15 and 60 min after the irradiation of mice shows that the radioprotective effect, though modest, was evident only in one case of elevated cAMP/cGMP ratio (the injection of 2-Mercaptoethylamine 2 min after the irradiation). Evident radioprotective effect occurs at the cAMP/cGMP ratio of about 170-200%; the ratio of about 130-140% corresponds to small radioprotection.

[Effects of a lymphocytic chalone-containing preparation on the mitotic activity of mouse thymocytes in vivo]. / Izuchenie vliianiia limfotsitarnogo keilonsoderzhashchego preparata na mitoticheskuiu aktivnost' timotsitov myshchei in vivo.

It has been shown that chalone-containing substance obtained from the rat spleen decreased the mitotic activity of mouse thymocytes upon its intraperitoneal administration to animals. The maximum inhibition was observed 45 min after the injection. Thus, the substance examined has the property of G2 chalone.

[Cyclic adenosine-3',5'-phosphate and guanosine-3',5'-phosphate in mouse plasma during administration of chemical compounds with different degrees of radioprotective effectiveness]. / Tsiklicheskie adenozin-3',5'-monofosfat i guanozin-3',5'-monofosfat v plazme krovi myshei pri vvedenii khimicheskikh soedinenii, obladaiushchikh razlichnoi protivoluchevoi éffektivnost'iu.

A study was made of seven radioprotective agents of different chemical classes (sulfur-containing, indolylalkylamines, and imidazol, urea and pyridasine derivatives) and also of their six structural analogs without radioprotective properties on the content of cyclic nucleotides in blood plasma and on the postirradiation survival of mice. There was a correlation between the ability of the preparations to increase the level of cyclic adenosine-3',5'-monophosphate and their radioprotective properties; with guanosine-3',5'-monophosphate, this correlation was absent.