Postradiation changes in the systems of active transport of ions in the CNS. Mitochondrial ATPase

The effect of lethal and superlethal doses of ionizing radiation (0.206, 0.309, and 9.288 C/kg) on ATPase activity of rat brain mitochondria has been investigated. The results obtained indicate that ionizing radiation causes appreciable, depending on the dose, changes in ATPase of brain mitochondria.     

Postradiation changes in the systems of active ion transport in the CNS. Na,K-ATPase

A study was made of the effects of irradiation with lethal (0.31 C/kg) and superlethal (12.9 C/kg) doses on Na,K-ATPase activity of various membrane formations in rat brain cortex. The results obtained indicated a significant increase in the activity of the enzyme at different times after irradiation.     

Postradiation changes in the functioning of the systems of lipid peroxidation and phospholipase hydrolysis in the cellular formations of the brain

A study was made of the effect of irradiation with lethal and superlethal doses on lipid peroxidation and endogenous phospholipase hydrolysis in the enriched fractions of neurons and glia. Severe and irreversible changes occurred in a lipid membrane component of both neuronal and glial fractions of the brain under the effect of ionizing radiation.     

Effect of x-rays on the pacemaker neurons of Helix pomatia

The effect of superlethal doses of ionizing radiation on exciting and electrical properties of giant neurons of the central nervous system of Helix pomatia has been investigated. At early times following irradiation the excitability does not significantly change whereas the membrane potential, resistance and pump-induced hyperpolarization increase. At later times, a stabilization of these parameters is followed by a diminution of resistance, a decrease of membrane potential and pump-induced hyperpolarization, and even the neuron death.     

Changes in metabolism of the nervous system in exposure to ionizing radiation at supralethal doses

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.     

The effect of low doses of ionizing radiation on the intermediate filaments and the Ca2+-activated proteolysis system in the rat brain

The immunochemical methods were used to study the effect of low-level radiation (0.00645 C/kg and 0.0129 C/kg) on the content and polypeptide composition of glial intermediate filament proteins (GIFP) in different rat brain areas. Changes in glial fibrillar acidic protein (GFAP) concentration were more significant with the dose of 0.0129 C/kg than 0.00645 C/kg. It is suggested that soluble GIFP is more susceptible to the effect of Ca(2+)-dependent proteinases, calpains, than the filament one is, and degrades as early as the first few hours following irradiation. However, low radiation doses were ineffective with respect to calpains activity in the animal brain. The increased Ca2+ concentration enhances considerably GFAP degradation under the effect of calpains I and II. It is suggested that with low radiation doses the rearrangements of glial intermediate filaments may occur due to activation of calpains by releasing Ca ions.     

Postradiation changes in the systems of active ion transport in the CNS. Potassium ion reaccumulation by surviving brain slices

The data are reported concerning the effects of ionizing radiation (0.155 C/kg, 0.206 C/kg, and 0.31 C/kg), A2 phospholipase and short-chain fatty acids that are indicative of an essential contribution of a membrane lipid component to the effect of radiation on Na-K pump of the neuron and the universality of the mechanisms of action of ionizing radiation on organisms differing in radiosensitivity.     

Radiation-induced suppression of the Bmp2 signal transduction pathway in the pluripotent mesenchymal cell line C2C12: an in vitro model for prevention of heterotopic ossification by radiotherapy

Heterotopic ossification is a common complication after total hip replacement. Clinical studies showed the effectiveness of radiation for prevention of heterotopic ossification. The mechanism of radiotherapy responsible for the reduction of heterotopic ossification is unclear. The purpose of this study was to study an analogue model showing a time- and dose-dependent effect of radiation. Using cells of the defined embryonic mouse cell line C2C12, the influence of ionizing radiation on the Bmp-induced signal cascade leading to osteogenic differentiation was analyzed. Binding of iodinated Bmp2 to the receptors, Smad1 activation, and alkaline phosphatase (ALP) activity were determined in cells with or without irradiation. The cytotoxic effect of radiotherapy was evaluated using viability tests. Radiotherapy reduced formation of the Bmp2/Bmp receptor complex. This effect was dependent on dose. The phosphorylation (activation) of Smad1 decreased after irradiation in a time-dependent manner, whereas the level of total Smads was not influenced by radiotherapy. The ALP activity decreased after radiotherapy. A dose of 7 Gy delivered 6 h before or after incubation with Bmp resulted in about a 30% decrease in ALP activity. No signs of cytotoxic effects were observed within the time window studied using doses of 0 to 20 Gy. The time- and dose-dependent effect of radiotherapy for prevention of heterotopic ossification known from the results of clinical studies has an analogue in the C2C12 cell model. The primary mechanism of radiotherapy seems to be an influence on cellular responsiveness to the Bmp2-induced osteoblastic differentiation. The results suggest a down-regulation of the Bmp2/receptor complex.     

The effect of low-level x-irradiation on the key enzymes of the active ion transport system in the cell

A study was made of the effect of ionizing radiation (0.013 C/kg) on Na, K- and Ca, Mg-ATPase activity in membranes of rat organs differing in radiosensitivity. It was shown that radiation mainly caused activation of enzymes that was most pronounced in brain membranes.     

Postradiation changes in the systems of active transport of ions in the CNS. Energy requirements for active transport

A study was made of the effect of irradiation with a superlethal dose of 9.288 C/kg on oxidative phosphorylation in morphologically and functionally different parts of the central nervous system. The CNS-syndrome was shown to develop against the background of a pronounced injury to energy processes in the brain. It is supposed that the impairment of the energy supply of active ion transport systems plays an important role in the dysfunction of the brain induced by high-level radiation.     

Pharmacologic correction of postradiation changes of pain sensitivity in rats

With radiation injury caused by superlethal doses of 150 Gy the analgesic effect of narcotic drugs decreases and the level of drug analgesia depends on the initial status of nociceptive reactions. The role of mu-opiate mechanisms in the development of postirradiation analgesia to thermal stimuli has been determined.     

The role of regulatory networks of the cell response to damages in radiation effects

In view of modern knowledge and concepts about components, function and mechanisms of response of cell molecular structures to damaging effects, response which is generating specialized modules of reactions, it is shown that main components of the mechanism of maintenance of genome constancy at ionizing radiation exposure are checkpoints of cell cycle, DNA repair and apoptosis. They operate under the control of a genetic system at participation of Tp53 gene, corresponding protein and of regulatory networks formed by cascades of mitogen-activated protein kinases (MAPK). At ionizing radiation exposure the MAPK special modules participate in formation of radiation effect: ERK 1/2 (extracellular signal-regulated kinase 1 and 2), JNK/SAPK (c-Jun N-terminal kinase/stress activated protein kinase) and p38 MAPK. Executing physiological functions of maintenance of normal life activity of cells, they do not lose this capacity after exposure to ionizing radiation, participating in formation of radiation effect in a wide range of doses, and are inactivated only by exposure to very high doses. It is concluded that in light of the modern data the main problem is not a problem of mechanisms of biological effect of ionizing radiation but a problem of biological mechanisms of radiation exposure.     

Protein kinase C zeta nuclear translocation mediates the occurrence of radioresistance in friend erythroleukemia cells

Friend erythroleukemia cells require high doses (15 Gy) of ionizing radiation to display a reduced rate of proliferation and an increased number of dead cells. Since ionizing radiation can activate several signaling pathways at the plasma membrane which can lead to the nuclear translocation of a number of proteins, we looked at the intranuclear signaling system activated by Protein Kinases C, being this family of enzymes involved in the regulation of cell growth and death. Our results show an early and dose-dependent increased activity of zeta and epsilon isoforms, although PKC zeta is the only isoform significantly active and translocated into the nuclear compartment upon low (1.5 Gy) and high (15 Gy) radiation doses. These observations are concomitant and consistent with an increase in the anti-apoptotic protein Bcl-2 level upon both radiation doses. Our results point at the involvement of the PKC pathway in the survival response to ionizing radiation of this peculiar cell line, offering PKC zeta for consideration as a possible target of pharmacological treatments aimed at amplifying the effect of such a genotoxic agent.     

Effect of ionizing radiation on the kinetic parameters of rat cerebral cortex Na, K-ATPase

A study was made of the effect of ionizing radiation of 10.3 and 180.6 mC/kg on kinetic parameters of the processes of activation of Na,K-ATPase of rat brain cortex by Mg-ATP-substrate and Na+ and K+ ions. The obtained results prompt an assumption that a conformational rearrangement occurs under the effect of ionizing radiation which is not identical after relatively small and lethal radiation doses.     

Modifying effect of ionizing radiation on the transmembrane transport of sodium ions in Ehrlich carcinoma tumor cells

The effect of a local X-irradiation on the transmembrane transfer of Na ions and activity of Na-K ATPase in Ehrlich ascites tumor cells has been investigated. Irradiation with doses of 0.05 and 0.15 C/kg are shown to change natrium ion transport. This effect is absent at a dose of 0.08 C/kg. A change in the rate of active transport correlates to some extent with the disturbance in Na-K ATPase occurring at the same radiation doses.     

Structure and functional changes in the gastric intramural nervous plexus in emotionally stressed rats exposed to low doses of long-term ionizing irradiation and lead

Changes in the catecholamine content in adrenergic fibres, acetylcholinesterase activity, and in the energy metabolism enzymes lactate dehydrogenase and succinate dehydrogenase in neurons of the gastric intramural plexus during emotional stress in rats a day after combined exposure to prolonged (30 days) ionizing radiation in a total dose 1.0 Gy and 0.6 mg/kg lead were studied. A decrease in catecholamines in adrenergic fibres and acetylcholinesterase and lactate dehydrogenase activity in neurons was observed. An enhanced sensitivity of the gastric intramural plexus after the prolonged exposure to small doses of ionizing radiation and lead in conditions of emotional stress was suggested.     

Effect of gamma irradiation on brain enkephalin hydrolase activity in the rat

A study was made of the effect of different radiation doses on the brain enzymes degrading enkephalins. Enkephalin aminopeptidase activity decreased during the first 60 min following irradiation with a dose of 774 X 10(-4) C/kg and increased after a dose of 3096 X X 10(-4) C/kg; enkephalinase A exhibited opposite changes. 48 hr after irradiation, enkephalin aminopeptidase activity exceeded the normal level, and no significant changes occurred in encephaliase A activity irrespective of the radiation dose.     

Effect of ionizing radiation on the functional state of Helix pomatia neurons. The systems of Na+ and K+ transport

The influence of ionizing radiation (5.16 C/kg) on passive and active Na+ and K+ transfer within the giant neurons of edible snail (Helix pomatia) has been investigated. It has been shown that ionizing radiation increases passive permeability of membranes, inhibits active ion transport, changes the number and the affinity of functionally active Na+,K+-ATPase molecules. The authors discuss the mechanisms of action of ionizing radiation.     

The linear no-threshold model does not hold for low-dose ionizing radiation

Almost all of the data on the biological effects of ionizing radiation come from studies of high doses. However, the human population is unlikely to be exposed to such doses. Regulatory limits for radiation exposure are based on the linear no-threshold model, which predicts that the relationship between biological effects and radiation dose is linear, and that any dose has some effect. Chromosomal changes are an important effect of ionizing radiation because of their role in carcinogenesis. Here we exposed pKZ1 mice to single whole-body X-radiation doses as low as 1 microGy. We observed three different phases of response: (1) an induction of inversions at ultra-low doses, (2) a reduction below endogenous inversion frequency at low doses, and (3) an induction of inversions again at higher doses. These results do not fit a linear no-threshold model, and they may have implications for the way in which regulatory standards are presently set and for understanding radiation effects.     

Characteristics of the development of radiation sickness in guinea pigs exposed to non-uniform irradiation in highly lethal doses

Certain peculiarities have been revealed in the development of radiation sickness in guinea pigs subjected to nonuniform irradiation with superlethal doses. With electron and gamma-neutron radiation LD50/1.5 was 116.11 and 114.48 Gy respectively, when delivered to whole body, and 133.40 and 111.72 Gy when delivered to the posterior part of the body.