[The influence of sodium nitrite on the osmoresistance of Chinese hamster cells].

We have previously demonstrated that incubation of V-79 cells in the medium containing the nitric oxide donor, NaNO2, increases cell resistance to damaging effect of gamma-rays, UV radiation and hyperthermia. In the present study, we investigated the effects of the nitric oxide donor on the sensitivity of V-79 cells to changes in osmomolarity of the medium by adding different amounts of sodium chloride or water. We found that pretreatment of the cells with NaNO2 resulted in a significant increase in the number of growing cells in 48 h after the treatment. The osmomolarity-dependent morphological changes in cultured cells were also substantially diminished following NaNO2 treatment. This effect could be observed under both hyper- and hypoosmosis, and was dependent on concentration of sodium chloride in hypertonic medium (being maximal under 0.17 M NaCl) and on the amount of water in hypotonic medium (being maximal under 1.1 times the dilution with water). In the experiments with increased osmomolarity, we found that the observed increase in the number of growing cells following NaNO2 treatment was accompanied with a significant increase of the mitotic index. These findings indicate that nitric oxide increases cell resistance to the damaging effects of osmotic shock in the way which is similar to the protective effect of these molecules against radiation and hyperthermia. Similarities in the effects of NaNO2 under different conditions leading to cell damage suggest that nitric oxide might serve as the universal factor participating in recovery of damaged cells and mediating increased cellular resistance to the damaging conditions.

[The influence of nitric oxide inductor (NaNO2) on the sensitivity of Chinese hamster cells to hyperthermia].

Formerly we reported the reduction of sensitivity to gamma- and UV-radiation in Chinese hamster cells of line 90 under the influence of nitric oxide inductor (NaNO2). Of interest was to learn if it possible to reduce the influence of hyperthermia on cells by means of NO inductor. A 1 h long incubation with this NO donor demonstrated an increased survival of cells heated up to 45 degrees C, and a decreased frequency of chromosomal aberrations in these. Employment of cycloheximide (CHE), an inhibitor of protein synthesis, and administration of CHE together with nitric oxide donor (NaNO2), equally increased the cell survival at hyperthermia. These and relevant literature data suggest that the demonstrated effect of exogenous NO may be associated with HSP70 protein. The noticed decrease in the number of chromosomal aberrations in heated cells under the influence of NO donor may play an important role in its modifying effect on cells at hyperthermia.

[Effect of nitric oxide donor (NaNO2) on the stability of non-transformed and malignant cells to ultraviolet and gamma-radiation]. / Vliianie donora oksida azota (NaNO2) na ustoichivost' netransformirovannykh i zlokachestvenno pererozhdennykh kletok k ultrafioletovomu i gamma-izlucheniiam.

A decreased sensitivity of the Chinese hamster cells (line V-79) to gamma-radiation under the influence of nitric oxide induction was shown elsewhere. This effect is connected hypothetically with post-radiation reparation of DNA. The investigation of the nitric oxide donor effect on sensitivity of these to UV-radiation is of interest, because this radiation is an important ecological factor of the environment. The question of retention of nitric oxide positive effect on UV and gamma-radiation sensitivity in malignant HeLa cells is no less actual, because these cells significantly differ from normal cells of line V-79. We demonstrated that the donor of nitric oxide enhances stability of the Chinese hamster cells (line V-79) to UV-radiation, as well as to gamma-radiation independently of the time of cell incubation with sodium oxide donor before or after irradiation. The inefficiency of nitric oxide as a factor increasing UV-stability of cells was shown for malignant HeLa cells. A 1 h long incubation of these cells with NO-donor before gamma-irradiation decreased the number of chromosome aberrations, and conversely, the addition of this agent to the HeLa cell culture after gamma-irradiation did not change the radiostability. It may be inferred that distinctions in behaviour of nitric oxide in cultures of V-79 and HeLa cells using UV-radiation may be explained by transformation of the latter special features of their damage, and by the following reparation.

[Increased efficacy of radiation protection against fission neutrons using unithiol]. / Povyshenie éffektivnosti khimicheskoi zashchity ot neitronov deleniia s pomoshch'iu unitiola.

It was found that the combination of unithiol (Sodium salt of 2,3-dimercapto-1-propansulfonic acid) with cystamine and AET diminished their toxicity. The optimum ratio for the antitoxic effect is 0.5 molar equivalent of unithiol per radioprotective 1.0 equivalent of thiol. Animals withstand big doses of protectors well, that gives an opportunity to use increased amounts of cystamine and AET. In the experiments with circular irradiation of male (CBA x C57B1)F1 mice weighing 18-22 g with fission neutrons (the neutron mean energy was 0.85 MeV, the contribution of gamma-quanta to the total was 25%, dose rate was 14 cGy/min) it was shown that the combination of unithiol with cystamine and AET enhances their radioprotective effect: the DRF of cystamine (150 mg/kg)--1.1, and the DRF of the combination of cystamine (300 mg/kg) with unithiol (152 mg/kg)--1.2; the DRF of AET (150 mg/kg)--1.2, the DRF of the combination of AET (300 mg/kg) with unithiol--1.4. Thus, the enhancement of dose of the radioprotectors, which was made possible as a result of their combination with unithiol, leads to enhancement of efficacy of chemical protection against fission neutron irradiation as much as 10-20%. Efficacy of AET is found to be comparable to efficacy of this protector in conditions of X-rays irradiation.

[Effect of unithiol on cystamine toxicity in dogs]. / Vliianie unitiola na toksicheskie éffekty tsistamina u sobak.

In experiments with dogs it was shown that administration of unithiol before administration of cystamine decreases toxic effect of the last: period of excitation induced by cystamine is shortened, the time of emetic reaction decreases and expression of the emetic reaction to this preparation is diminished, the recorded EKG changes of conditions of heart decrease.

[Experience in the search of new prolonged-action radiation-protective agents]. / Opyt izyskaniia novykh radiozashchitnykh veshchestv prolongirovannogo deistviia.

The cysteamine derivative-guanidinoethanesulfanylthiosulfuric acid was demonstrated to have radioprotective properties protecting mice against X-rays and fission neutron irradiation hazard. Radioprotective efficacy shows itself for 2 hours after i.p. and p.o. administration of the preparation. It was established an opportunity of the prolonged protective action of gammaphos as a result of its cross-linking to dextran. The preparation has a radioprotective action on X-ray and neutron irradiation.

[Decrease of toxic effects of aminothiol radiation-protective agents and increase of chemical protection action against ionizing radiation by the use of unithiol]. / Snizhenie toksicheskogo deistviia aminotiolovykh radioprotektorov i povyshenie éffekta khimicheskoi zashchity ot ioniziruiushchei radiatsii s pomoshchiu unitiola.

It has been shown that unithiol diminishes toxic action of cysteamine, AET, and disulfide of WR-1065 on mice. This permits to enhance protection of animals against X-rays by increasing of protector doses. The effect of unithiol on cysteamine action in rats was the same. Antitoxic effect of unithiol on cysteamine was shown both at i.p. and p.o. protector administration. The effect was also revealed in Chinese hamster V-79 cell culture. Combined disulfide of cysteamine and unithiol was synthetized, which ensures effective prolonged protection against ionizing radiation.

[The direct action of high doses of gamma quanta and neutrons of different energies on the sympathetic ganglion neurons in the frog]. / Neposvredstvennoe deistvie vysokikh doz gamma-kvantov i neitronov raznoi énergii na neirony simpaticheskogo gangliia liagushki.

Irradiation of isolated frog sympathetic ganglia IX-X with high doses caused a long-term depolarization of a single ganglion cell and increase of synaptic activation threshold. The radiation effects observed were not accompanied by the transmission failure. The authors suggest that the changes in the synaptic mechanisms play a minor role in the development of the CNS syndrome.

[Action of high and superhigh doses of fission neutrons and gamma quanta on the central noradrenergic formation of the brain--on the locus coeruleus (the blue spot)]. / Deistvie vysokikh i sverkhvysokikh doz neitronov deleniia i gamma-kvantov na tsentral'noe noradrenergicheskoe obrazovanie golovnogo mozga--locus coeruleus (goluboe piatno).

Most of the blue spot neurons of Wistar rats exhibited a pronounced central chromatolysis 24 h following irradiation with fission neutrons (above 100 Gy) and gamma-quanta (above 200 Gy). The changes in the mesencephalic nucleus of the trigeminal nerve were distinct on day 2 after 200 Gy gamma-irradiation. The number of the modified nervous cells in these regions was higher than that in other brain parts.

[Indices of the status of the cholinergic processes in the rat sensorimotor cortex and caudate nucleus at early periods after gamma-irradiation at a dose of 150 Gr]. / Issledovanie nekotorykh pokazatelei sostoianiia kholinérgicheskikh protsessov v sensomotornoi kore i khvostatom iadre golovnogo mozga krys v rannie sroki posle gamma-oblucheniia v doze 150 Gr.

An insignificant increase in the content of acetylcholine-like substances was registered in the rat brain cortex and caudate nucleus 15 min after whole-body gamma-irradiation with a dose of 150 Gy. After 24 h, the number of these substances appreciably decreased. Total acetylcholinesterase activity in the above brain parts gradually decreased throughout the entire period of observation. These indices changed more markedly in the caudate nucleus than in the cortex of the brain.

A radiomodifying effect of acute hypoxia on neutron-irradiated mice and dogs.

Anoxia increased the survival of neutron irradiated mice with DMF = 1.66. As to haemopoietic stem cells neutron irradiated in vivo, DMF was 1.8. With X-irradiation DMF was 2.49 and 2.94, respectively. Anoxia decreased the damage of the intestinal mucous membrane after a whole-body neutron irradiation with a dose 3.0 Gy. A protective effect of acute hypoxia was demonstrated on dogs exposed to fast neutrons (4.0 Gy). Breathing of 10% gas hypoxic mixture protected more than half of the exposed animals from death and provided the development of a light form of radiation sickness instead of a serious one.

[Dynamics of changes in the ultrastructure of the rat cerebral cortex in the early period of acute radiation sickness caused by neutron irradiation]. / Dinamika izmenenii ul'trastruktury kory golovnogo mozga krys v rannie sroki ostroi luchevoi bolezni, vyzvannoi neitronnym oblucheniem.

A 24-hour electron microscopic examination of neuronal and capillary ultrastructure in sensorimotor complex was performed after whole-body neutron irradiation of mature rats in the dose of 10 Gy. The results suggest that postradiation neuronal changes, observed for 6 hours after irradiation, are mainly caused by direct effect of ionizing radiation. At later terms this process is influenced by blood capillary lesions. The effect of neutron irradiation at the ultrastructural level is similar to that of rarely ionizing radiation.

[Effect of hyperthermia on the radioprotective action of cysteamine and isoproterenol]. / Vliianie gipertermii na radiozashchitnoe deistvie tsisteamina i izoproterenola.

Heating of mouse bone marrow cells up to 42 degrees C was shown to increase their radiosensitivity (DMF = 0.80 +/- 0.12). At this temperature, the radioprotective efficiency of cysteamine was lost completely (DMF = 0.78 +/- 0.09), and radioprotective activity of d,l-isoproterenol significantly decreased (DMF declined from 2.41 +/- 0.23 to 1.67 +/- 0.16). It is assumed that the radioprotective effect of cysteamine on mammalian cells is associated with the processes of the postirradiation DNA repair for just these processes are inhibited by heating. The mechanism of action of a beta-agonist of isoproterenol is perhaps only partially associated with DNA repair.

[Effect of small doses of roentgen radiation on the spontaneous impulse activity of the hippocampus in vitro]. / Deistvie malykh doz rentgenovskogo izlucheniia na spontannuiu impul'snuiu aktivnost' gippokampa in vitro.

X-Irradiation of rat hippocampus in vitro with low doses accelerated spontaneous impulse passage without concomitant changes in synaptic activity. There was a negative correlation between the original frequency of neuron discharges and the degree of quickening the impulses in response to the effect of radiation. Perfusion of slices by a noncalcium solution blocked the synaptic transmission but did not influence the response to the effect of ionizing radiation.

[Dynamics of the early ultrastructural changes in sensorimotor cortical neurons of the rat brain after exposure to high doses of gamma-neutron radiation]. / Dinamika rannikh izmenenii ul'trastruktury neironov sensomotornoi zony kory golovnogo mozga krys posle deistviia vysokikh doz gamma-neitronnogo izlucheniia.

At early times (15 min to 6 h) after whole-body gamma-neutron irradiation of mature rats with a dose of 10 Gy reactive changes occur in neurons of the sensimotor cerebral cortex which can be interpreted as a manifestation of the enhancement of functional and metabolic activity of nerve cells followed by inhibition thereof.

[Radiomodifying effect of acute hypoxia in neutron-irradiated dogs]. / Radiomodifitsiruiushchee vliianie ostroi gipoksii pri neitronnom obluchenii sobak.

A pronounced protective effect of acute hypoxia was demonstrated on dogs exposed to fast neutrons (4.0 Gy). Breathing of 10% gas hypoxic mixture protected more than half of the exposed animals from death and provided the development of a light form of radiation sickness instead of a serious one. Possible mechanism of the effect observed are discussed.

[Mechanisms of action of high and superhigh doses of gamma-quanta and neutrons on the central nervous system]. / K issledovaniiu mekhanizmov deistviia vysokikh i sverkhvysokikh doz gamma-kvantov i neitronov na tsentral'nuiu nervnuiu sistemu.

Wistar rats were exposed to gamma-quanta (60Co, 100-400 Gy) and neutrons (100-200 Gy). The C. N. S. syndrome was shown to develop the neuron lesions being relatively minor. With a reference to this index, the RBE of neutrons was 1.75. The permeability of blood vessels of the brain was decreased during the development of the C. N. S.-syndrome. Disturbances in the functional state of neurons and interneuron reactions, including the changes in the mediator metabolism (these changes were manifested by the increased GABA content of the cerebellum), play, in all appearance, an important role in the impairment of the brain function under the effect of high doses of neutrons and gamma-quanta.

[Modifying effect of deep hypoxia on neutron-irradiated mice]. / Modifitsiruiushchee vliianie glubokoi gipoksii na éffekty neitronnogo oblucheniia myshei.

Deep hypoxia was shown to influence the survival of animals, the state of the small intestine mucosa and the haemopoietic system. DMF (LD50/30) was 2.49 and 1.66 with X- and neutron radiation, respectively. As to haemopoietic stem cells X-irradiated in vivo, D0 was 0.96 +/- 0.04 Gy (control) and 2.82 +/- 0.14 Gy (anoxia). With neutron irradiation, D0 was 0.44 +/- 0.01 Gy and 0.8 +/- 0.03 for the control and experimental animals respectively.