Effect of ionizing radiation on the functional state of the vascular-thrombocytic component of the hemostasis system

The influence of ionizing radiation (gamma-rays 60Co) on aggregation activity of the vascular wall and functional (aggregation) platelet activity was studied in the course of the development of acute radiation sickness. The decrease in the aggregation properties of the vascular wall and high functional activity of platelets were inversely proportional, correlating with the periods of acute radiation sickness development and depending on the radiation dose. It is suggested that the changes detected may play a role in the pathogenesis of the development of the postirradiation thrombohemorrhagic syndrome.     

Hydroxylating activity of rat liver microsomes in the period of acute phase protein formation in radiation sickness

At the height of radiation sickness (7-8 days after irradiation) the accretion of proteins of "acute phase" in rat blood was accompanied by diminution of diminution of hydroxylating activity of microsomes determined by the rate of aminopyrine demethylation. There was an invert correlation between these two indices, and the correlation coefficient was -0.9.     

The dynamic content of prostaglandins and cyclic nucleotides in the blood of irradiated dogs and monkeys

In experiments with dogs and monkeys a study was made of the dynamics of the content of prostaglandins (PG) and cyclic nucleotides after gamma irradiation. In dogs irradiation with lethal doses (3.1 and 50 Gy) caused a short-term, evidently stress growth of cAMP, PGE and PGF2 alpha levels. At the height of radiation sickness PGF2 alpha and cGMP content decreased considerably. Irradiation of monkeys with a nonlethal dose of 3.2 Gy changed PGE and PGF2 alpha levels to a lesser extent, while concentrations of cyclic nucleotides varied but their ratio remained stable.     

Changes in the dog endocrine system in the hematopoietic form of radiation sickness

The endocrine status of the organism estimated by the cortisol, insulin and triiodothyronine content of blood considerably changes during radiation sickness. The most pronounced changes in the endocrine status occur during the primary response and at the height of radiation sickness. The endocrine status test may be used in the individual radiosensitivity prognosis.     

Several indices of the peripheral immune system in clean up team workers and patients who survived acute radiation disease 5 years after effects of the radiation accident factors]

A group of liquidators and patients survived acute radiation sickness (ARS) was studied five years after the effect of radiation factors resulted from the Chernobyl A.P.S. disaster. Studied were the number of T-lymphocytes (SD2+, SD3+, SD5+), subpopulations SD16+ and SD25+, the content of SD16+ and SD25+ lymphocytes and B-cells, as well as the levels of serum IgM, A, G; determined was the concentration of serum alpha 1-thymosin. A decrease was noted in the number of T-cells of the examined patients, with respect to all markers studied: the number of SD4+ cells was found decreased in patients with ARS sequelae and normal in liquidators. The decrease in serum alpha 1-thymosin was a function of dose. Dynamics of changes in the T-cells of the examinees may reflect the new trends in the radiation response of T-lymphocytes which were not directly related to initial damages to the latter. The injury to the stroma of the thymus and especially to its epithelial cells may be the basis for later postirradiation damages to the immune system. The decrease in the concentration of alpha 1-thymosin in the blood serum of the examinee is the manifestation of the thymus hypofunction. In liquidators and patients with the ARS sequelae the number of SD25+ cells increased markedly indicating the existence of the source of endogenous cell activation. The content of B-lymphocytes in all studied groups of patients was reduced which may serve as a criterion of chronic stress.     

Chromatin breakdown in the white blood cells of rats during irradiation and in combined radiation injury under cystamine protection

The polydeoxyribonucleotide (PDN) level in leukocytes of peripheral blood of rats treated with cystamine adequately reflects the severity and outcome of radiation sickness. Preventive application of cystamine against the combined effect of ionizing radiation and heat decreased the PDN level in white blood cells but did not influence the survival of animals.     

Changes in the concentration of serum fibronectin in irradiated animals

A study of the level of fibronectin in blood serum of Wistar rats at different times after gamma-irradiation (7.5 Gy) has demonstrated a considerable increase in its concentration after 3 days. This increase is a function of radiation dose absorbed (within the range from 1 to 10 Gy). The most pronounced changes are observed with serious and extremely serious forms of acute radiation sickness. The administration of cycloheximide 48 h after irradiation removes completely the increase in the level of blood serum fibronectin.     

Individual immunological parameters in clean-up team members and patients with sequelae of acute radiation sickness 5 years after the effects of the Chernobyl accident]

A study was made of deviations, beyond 1 sigma and 1.5 sigma of a mean value (M) of a donor group, in individual immunological parameters (for instance, the number of CD5+, CD2+, CD4+, CD8+, CD25+ and B-cells; alpha 1-thymosin concentration; and autoantibody titers to antigens of epithelial reticulum cell cytoplasm) in patients suffered acute radiation sickness (ARS) and liquidators of Chernobyl NPP accident. The radiation damage to the immune system was reliably detected in the affected subjects examined: they exhibited a decrease in the alpha 1-thymosin level below M = -1.5 sigma and in absolute B cellularity below M = -1 sigma; and increase in the number of CD25+ cells and in the level of serum autoantibodies to antigens of thymus epithelial reticulum cell cytoplasm. When several parameters selected were examined simultaneously the frequency of recording the deviations in merely one of them markedly increased.     

Effect of ionizing radiation on the synthetic activity of blood system cells in ground squirrels in different physiological states of animals

The functional (synthetic) activity of blood lymphocytes and bone marrow haemopoietic cells in ground squirrels during the annual cycle as well as in hibernating and awaken animals in winter have been studied by fluorescent microspectrometry. The effect of ionizing radiation on animals in different functional states of the hibernation-arousal bout was investigated too. It was shown that the synthetic activity (parameter alpha) in blood lymphocytes was minimal in hibernating state in winter and maximal in active euthermic spring animals, then slightly decreased in June and more considerably decreased in the prehibernating autumn period. In awake animals in winter, the values of parameter alpha reached the same values as in summer. The changes of parameter alpha in bone marrow haemopoietic cells were essentially the same: the minimal values were observed in the prehibernation autumn period and in awake animals in winter the alpha values were slightly higher than in active euthermic animals in summer. The maximal synthetic activity in bone marrow haemopoietic cells in active euthermic spring animals is due mainly to cells in G1-G2 phases of the cell cycle. The decrease of the synthetic activity in summer is a result of the cell transition from G2 to mitosis and transition of a part of cells to G0 When investigating the hibernation-arousal bout in ground squirrels in winter, during arousal, we found two stages considerably differing in both the values of parameter alpha in bone marrow haemopoietic cells and the number of blood cells. The synthetic activity and the total number of blood and bone marrow cells in ground squirrels irradiated in the state of deep hibernation did not differ significantly from the state of non-irradiated hibernating animals. The negative effect of radiation appeared upon the arousal of these animals but it was expressed to a lesser degree in comparison with the animals irradiated in the active state. It was found that the acute irradiation of animals during arousal from hibernation in the second stage caused the most pronounced functional inactivation and cell death. The physiological state of ground squirrels subjected to ionizing irradiation at different phases of the hibernation-arousal bout plays a determining role in the changes of the qualitative and quantitative characteristics of blood system cells. Thus, the hypometabolic state of ground squirrels in hibernation is a factor of protection from the action of ionizing radiation on the organism and the immune system.     

5-nucleotidase activity in rat leukocytes, erythrocytes and blood serum during radiation sickness

A study of 5-nucleotidase activity in the formed elements and blood serum of rats 1, 3, 7, 15 and 30 days after X-irradiation has demonstrated that it was increased in leukocytes at early times and inhibited at later times of the development of radiation sickness. In erythrocytes, inhibition of 5-nucleotidase activity was most pronounced on the 3d day. In blood serum, the enzyme activity was virtually invariable. The addition of ATP to the incubation medium normalized 5-nucleotidase activity.     

Mechanism of reduced binding capacity of plasma corticosteroid-binding globulin in acute radiation sickness

Injection of various doses of thyroxin to rats was shown to increase a binding capacity of corticosteroid-binding globulin (CSG) of blood plasma after irradiation with doses of 650 and 800 R. The effect of thyroxin was most pronounced at a mid-lethal dose of 650 R and at the early stage of radiation sickness.     

EPR study of the blood of animals during an acute radiation lesion

The intensity of the ESR signal of methemoglobin, Fe3+-transferrin, and Cu2+-ceruloplasmin in blood and spleen of mice exposed to 6 Gy radiation was shown to undergo considerable changes at early times of acute radiation sickness.     

Combined effect of normobaric hyperoxia and vibration on the radiosensitivity of animals

In experiments with hybrid mice (CBA X C57B1)F1 and F2(CBWA), a study was made of the combined effect of normobaric hyperoxia and vibration on sensitivity of the organism to gamma-radiation. A single and protracted (for 5 days, daily) vibration before irradiation aggravated acute radiation sickness. A modifying effect of hyperoxia on the development of the intestinal form of radiation sickness was the same as that observed under the effect of vibration. In the experiments with tetrahybrids, the combined effect of the two factors aggravated drastically the intestinal syndrome of acute radiation sickness (DMF = 1.24).     

The information value of clinico-hematologic criteria for the early diagnosis of acute radiation sickness in pig-tailed macaques

Ten pig-tailed monkeys (Macaca nemestrina) were subjected to 60Co radiation at a dose of 6.0-6.5 Gy and a dose rate of 1.2 Gy/min. Acute radiation sickness has developed in the monkeys causing their death on the 16-20 day. In spite of this, the initial reaction was weakly expressed and according to its manifestation it was impossible to evaluate severity and possible outcome of the lesion. At an early stage of the disease (6-24 hours) insufficient was uranin fluorescence in blood plasma, but more informative were the changes in adhesive properties of leukocytes the dynamics of lymphocytes (lymphopenia), reticulocytes (reticulocytopenia) and shifts in reticulograms (increased per cent of juvenile forms).     

The cytogenetic and hematotoxic effect of cesium-137 incorporated in the rat body]

The influence of incorporated 137Cs on peripheral blood cells was studied at different times after a single per os administration to rats. Moderate lymphopenia occurred in 26 days. A 30-70% increase in the number of aberrant lymphocytes was revealed throughout the entire period of observation (up to 547 days). Rats are suggested to develop a pronounced immune depression and chronic radiation sickness.     

Effect of ionizing radiation on the superoxide dismutase content and turnover in the rat liver

A study was made of the effect of ionizing radiation on the activity, concentration, biosynthesis, transport and disintegration of cytosol and mitochondrial forms of superoxide dismutase in rat hepatocytes. It was shown that after total-body X-irradiation there was a tendency toward a decrease in the activity of the enzyme while its concentration in the mitochondrial fraction increased. Stimulation of the processes of biosynthesis, transport and disintegration of superoxide dismutase in both fractions was also detected. The data obtained are discussed with regard to the development of radiation sickness.     

The modifying effect of novocaine on the clinical manifestations of the intestinal form of radiation sickness]

On rats and dogs exposed to absolute lethal doses of X-irradiation (rats--10, 12 Gy; dogs--15 Gy sublethally) it has been shown that novocaini injection to animals immediately after radiation exposure reduces the primary radiation reaction and at the same time shifts the changes in morphofunctional state of peripheric blood on 24 hours, reduces the symptoms of acute radiation sickness, increases the average life length of the animals on 1,5 days. A conclusion concerning the expressed therapeutic influence of intraperitoneal novocaini injection immediately after radiation has been drawn.     

Biochemical reception and ionizing irradiation of the body

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).     

NMR spectroscopy based metabolic profiling of urine and serum for investigation of physiological perturbations during radiation sickness

Radiation accidents are rare events that induce radiation syndrome, a complex pathology which is difficult to treat. In medical management of radiation victims, life threatening damage to different physiological systems should be taken into consideration. The present study was proposed to identify metabolic and physiological perturbations in biofluids of mice during different phases of radiation sickness using ¹H nuclear magnetic resonance (¹H NMR) spectroscopy and pattern recognition (PR) technique. The ¹H NMR spectra of the biofluids collected from mice irradiated with 5 Gray (Gy) at different time points during radiation sickness were analysed visually and by principal components analysis. Urine and serum spectral profile clearly showed altered metabolic profiles during different phases of radiation sickness. Increased concentration of urine metabolites viz. citrate, α ketoglutarate, succinate, hippurate, and trimethylamine during prodromal and clinical manifestation phase of radiation sickness shows altered gut microflora and energy metabolism. On the other hand, serum nuclear magnetic resonance (NMR) spectra reflected changes associated with lipid, energy and membrane metabolism during radiation sickness. The metabonomic time trajectory based on PR analysis of ¹H NMR spectra of urine illustrates clear separation of irradiated mice group at different time points from pre dose. The difference in NMR spectral profiles depicts the pathophysiological changes and metabolic disturbances observed during different phases of radiation sickness, that in turn, demonstrate involvement of multiple organ dysfunction. This could further be useful in development of multiparametric approach for better evaluation of radiation damage as well as for medical management during radiation sickness.