[Nonmonotonous metabolic response of mammalian cells and tissues to ionizing radiation]. / Nemonotonnost' metabolicheskogo otveta kletok i tkanei mlekopitaiushchikh na vozdeistvie ioniziruiushchei radiatsii.

Changes in the activity of ornithindecarboxylase in various tissues and in the amount of catecholamine in rat hypothalamus by the action of acute and chronic ionizing radiation were studied. A nonmonotonous relationship between the metabolic parameters of animal tissues and cells and the radiation dose was revealed. It was assumed that the nonmonotonous character of the dose-response dependence results from the nonmonotonous time course of the metabolic response to irradiation. It was also assumed that living systems have the property of responding to stress agents by nonmonotonous changes in metabolism. In the case of acute irradiation, this response manifests itself as oscillations of metabolic parameters about the control. The oscillations occur with a particular amplitude and periods, which vary with radiation dose, and damp out with time. As a result, in a fixed time interval, the dose-response curve may be nonmonotonous. Reverse dose-response relationships are also possible. In the case of chronic irradiation, the metabolic and functional parameters oscillate throughout irradiation time, and a modification of the response occurs. A prolong exposure to ionizing radiation causes strong changes in the metabolism of lipids of cell membranes, organelles and chromatin, as well as in the functional properties of some mammalian cells and tissues. The necessity of constructing quantitative models for explaining the nonmonotonous dose-response dependence is discussed.

Nuclear and chromatin lipids: metabolism in normal and gamma-irradiated rats.

The data on nuclear and chromatin lipid metabolism are reviewed. The amount of neutral lipids and phospholipids in nuclei of rat thymus, liver and neocortex neuron as well as the amount of lipids in rat thymus and liver chromatin are described. The metabolic responses of nuclear and chromatin lipids from thymus to different doses and dose rates of gamma-irradiation of rats are discussed. In most cases, the nuclear and chromatin lipid responses are distinct. Changes in nuclear and chromatin lipid metabolism in response to gamma-irradiation are suggested to connect with the signal transduction pathway and the regulation of the transcriptional and replicative chromatin activity. The influence of beta-carotene and picrotoxin on rat liver nuclear lipids and neocortex neuronal nuclear lipids, respectively, was analyzed. The possible involvement of the lipid traffic in the chromatin lipid responses to gamma-irradiation and other agents is suggested.

Effect of chronic gamma-irradiation and beta-carotene on lipid metabolism in presynaptic membranes in rat brain.

Lysophosphatidylcholine is involved in radiation-induced modulation of presynaptic membranes in rat brain. High sensitivity of the cortical integrative functions to chronic low-dose gamma-irradiation is demonstrated. beta-Carotene produced a protective effect during chronic irradiation.

Nonmonotonous Changes in Metabolic Parameters of Tissues and Cells under Action of Ionizing Radiation on Animal.

A nonmonotonous relationship between changes of metabolic parameters of tissues and cells of animal and radiation dose were discussed. Under acute irradiation of animals the nonmonotonous dose-response curve for metabolic parameters of tissues and cells were found. The nonmonotonous dose-response curves of metabolic and functional tissues and cells parameters were also revealed upon chronic irradiation of animals at a low dose-rate. The nonmonotonous shape of dose-response curves may be explained on the basis of nonmonotonous kind of the time-course of metabolic response after irradiation. Living cells were supposed to possess a fundamental property in response to action of different stress agents by nonmonotonous changes of cell metabolism. This response was damping in time oscillation of the value of metabolic parameters around the normal level. Amplitudes and periods of oscillations in these changes of metabolic parameters could be observed. In case of chronic irradiation at a low dose-rate the metabolic and functional parameters showed some modified oscillation during irradiation. The nonmonotonous type of changes in metabolic and functional parameters of tissue and cell by chronic low dose-rate irradiation threw some new light on the peculiarities of biological effects of chronic irradiation.

[Behavior reactions and lipids of brain synaptic membranes of rats under chronic exposure to gamma irradiation]. / Povedencheskie reaktsii i lipidy sinapticheskikh membran golovnogo mozga u krys pri khronicheskom vozdeistvii gamma-izlucheniia.

The effects of low level chronic ionising irradiation (12.9 cGy/day on the sensory attention to the stimuli of different modalities (somatosensory, visual, odor) of Wistar rats were studied. Analysis of animals behaviour was made after they had received the different doses of irradiation: 4, 6, 8, 10, 15 and 20 Gy. It was founded, that the attention and exploratory activity of rats is significantly decreased up to 20-30% after 4-6 Gy. The irradiation doses 8 Gy did not change animal behaviour as compared to control animals, but doses 10, 15 and 20 Gy decreased the exploratory activity as well as sensory attention of rats to 3-5-times as compared to previous dose. Such a wave-like way of behaviour reflects the functioning of an adaptive mechanism. Biochemical data indicated that after 5 months of the irradiation (dose 20 Gy) the level of phospholipids, lysophosphatidylcholine, phosphatidylethanolamine, phosphatidylcholine, cholesterol were decreased.

[The lipid composition of the membrane of the brush border in the rat small intestine in the late period after gamma irradiation]. / Lipidnyi sostav membrany shchetochnoi kaimy tonkogo kishechnika krys v otdalennye sroki posle gamma-oblucheniia.

The lipid composition of membrane of the small intestine brush border was studied 1, 2, 3 and 6 months after the whole-body fractionated gamma irradiation of the one-month-old rats of 80 g weight with a dose of 6 Gy (2 Gy x 3 at a week intervals). Three months after exposure the amount of cholesterol, total phospholipids, phosphatidylcholine, phosphatidyl-ethanolamine in brush border membrane was the same as in control. The role of phospholipids and cholesterol catabolism suppression in membrane regulatory function disturbances after irradiation is discussed.

[The effect of beta-carotene on the cytoplasmic membrane lipids of cells in rats under chronic gamma irradiation]. / Vliianie beta-karotina na lipidy tsitoplazmaticheskikh membran kletok krys pri khronicheskom gamma-obluchenii.

Chronic gamma irradiation of rats at a dose rate of 12.9 rad/day for 155 days (total dose 20 Gy) did not change the cholesterol level in the brush border membrane of the small intestine. Maintenance of rats on a beta-carotene-enriched diet (daily throughout the irradiation period, at a diurnal dose of 3 mg/kg body weight produced an increase in cholesterol levels in the small intestinal brush border membranes. The phospholipid level after gamma irradiation alone did not change, but it was increased in gamma-irradiated rats fed with carotene, this increase being most pronounced for sphingomyelin. Beta-carotene decreased the cholesterol/phospholipid ratio in the brush border membrane of irradiated rats. Activation of lipid synthesis (as seen from inclusion of 2-14C-acetate in the epitheliocyte lipids of irradiated animals) and no influence of beta-carotene on the inclusion of the label in small intestine epitheliocytes of irradiated animals have been revealed. In the presynaptic membranes of brain nerve endings, chronic gamma irradiation of animals produced a deep fall of cholesterol and phospholipid levels. Also, a tendency was revealed for stimulation of transport of the neurotransmitter amino acids GABA and L-glutamate across the presynaptic membranes of nerve endings. Beta-carotene normalized the phospholipid and cholesterol levels in brain presynaptic membranes of irradiated rats, as well as decreased L-glutamate transport. It is assumed that the modifying and normalizing effects of beta-carotene on the lipid exchange of plasma membranes upon chronic irradiation of animals and permanent introduction of the drug are associated with the radioprotector activity of beta-carotene.

[The effect of gamma irradiation at sub- and supralethal doses on the lipid composition of the mucosa and of the brush border membrane of the small intestine in rats]. / Vliianie gamma-oblucheniia v sub- i sverkhletal'noi dozakh na lipidnyi sostav slizistoi obolochki i membrany shchetochnoi kaemki tonkogo kishechnika krys.

A study was made of the amount of cholesterol and its ethers (phosphatidyl choline, phosphatidyl ethanolamine, sphingomyelin, phosphatidyl serine, and phosphatidyl inositol) in mucosa and membrane of the small intestine brush border 24 h after 4 Gy and 2 h after 20 Gy irradiation. No changes in the lipid content of mucosa and membrane of the brush border were noted after 4 Gy irradiation. Exposure to 20 Gy radiation doubled the number of cholesterol ethers and made the number of individual phospholipids and cholesterol increase by nearly 1.5 times. The amount of phosphatidyl serine in the brush border membrane increased by almost 3 times; the concentration of other lipids increased by nearly 1.5 times; cholesterol/phospholipid ratio was unchangeable.

[Lipid metabolism in rat tissues after irradiation at doses causing interphase cell death]. / Lipidnyi obmen v tkaniakh krys pri dozakh oblucheniia, vyzyvaiushchikh interfaznuiu gibel' kletok.

Irradiation of animals with doses eliciting interphase death of 50-80% of cells activates lipogenesis and decreases the cholesterol content of cells. Cholesterol synthesis is activated after irradiation with doses causing death of 50% of cells: a further increase in radiation dose decreases the cholesterol synthesis. It is assumed that as membranes are destructed by radiation the adaptive lipogenesis activated to restore them.

[Comparative study of lipid transfer between cell organelles using lipid-transfer proteins in vitro]. / Sravnitel'noe issledovanie perenosa lipidov mezhdu organellami v kletke i s pomoshch'iu lipidperenosiashchikh belkov in vitro.

The transfer of de novo synthesized lipids from microsomes to lipid non-synthesizing membranes was studied in vivo and in vitro from the ratios of specific radioactivities of [14C]cholesterol, [14C] and [32P]phosphatidylcholine and [32P]phosphatidylethanolamine in the nuclei and mitochondria to that in microsomes. The radioactivity of lipids transferred from microsomes to mitochondria and nuclei was identical both in vitro and in vivo and when the lipid-exchange protein of the 105 000 g supernatant was used. Acceleration of lipid metabolism in the liver of gamma-irradiated rats was concomitant with the increase in the rate of labeled cholesterol transfer cation to liver cell nuclei and mitochondria, but remained unchanged in in vitro studies involving lipid-exchange protein. The reduction of phosphatidylethanolamine transfer to the nuclei in vitro and in vivo diminished in the same way. The existence in the cell of mechanisms of transfer of de novo synthesized cholesterol other than lipid-exchange protein is postulated.

[Lipid transport activity of liver cell cytosol at early periods following gamma-irradiation of rats]. / Lipidperenosiashchaia aktivnost' tsitozolia kletok pecheni v rannie sroki posle gamma-oblucheniia krys.

A study was made of the rate of the transfer of phospholipids and cholesterol between 14C-microsomes and mitochondria of gamma-irradiated rat liver. Cytosole and cell organelles of nonirradiated and irradiated rat liver were combined to reveal the increase in the cholesterol-transfer activity of liver cell cytosole 60 min following irradiation (12 Gy). Roughly purified lipid-transfer proteins from liver cytosole of control rats transported lipids, at an equal rate, between organelles isolated from liver cells of control and exposed rats. Radiation modification of cell organelle membranes was only detected upon the reaction with cytosole from the irradiated rat liver.

[Therapeutic effect of vegetable oils and ubiquinone-9 on radiation injuries]. / Terapevticheskoe deistvie rastitel'nykh masel i ubikhinona-9 pri luchevom porazhenii.

The comparison was made of the protective (the administration 3 h before irradiation with a dose of 7.3 Gy) and therapeutic (the administration immediately and later after exposure) effects of soya oil (150 mg/kg) and oil solution of ubiquinone-9 (100-200 mg/kg) on survival of exposed rats. It was shown that soya oil and ubiquinone-9 increased the survival rate of rats when administered before and, to a lesser extent, immediately after irradiation. Corn oil administered immediately after exposure increased the survival rate as well. DMF for the therapeutic effect of soya oil solution of ubiquinone-9 was 1.08.