[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.

Ornithine decarboxylase in organs of rat following chronic gamma-irradiation at low dose-rates.

PURPOSE: To investigate the consequence of continuous low dose-rate exposure to gamma-rays on ornithine decarboxylase (ODC EC 4.1.1.17) activity in organs of rat. MATERIALS AND METHODS: Young male Wistar rats were irradiated at 1.1, 2.1 and 12.9 cGy/day in the dose ranges of 9-165, 17-315 and 100-2000 cGy, respectively, in a specially designed chamber. ODC activity was determined in 20000 g supernatant fluid of thymus, spleen and lung by measuring the release of 14CO2 from L-[1-14C]ornithine. RESULTS: Chronic y-irradiation modulated ODC activity. It decreased at low cumulated doses (after 8 and 15 days of exposure). At longer periods after chronic irradiation (after 45 and 90 days), ODC activity was restored up to control levels despite increasing values of cumulated doses. On day 150 a similar increase in ODC activity in spleen 2.1 cGy/day and in lung at 12.9 cGy/day was observed. CONCLUSIONS: These studies showed a non-monotonic pattern of the 'dose-response' curve. The results were interpreted in terms of the triggering of a homeostatic system.

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.

[Ornithine decarboxylase in the organs of rats under chronic exposure to gamma radiation at a low dosage rate]. / Ornitindekarboksilaza v organakh krys v usloviiakh khronicheskogo vozdeistviia gamma-izlucheniia maloi moshchnosti doz.

Chronic exposure of rats to gamma-irradiation at the dose rates of 1.1, 2.1, and 12.9 cGy/d in the dose ranges of 9-165, 17-315, and 100-2000 cGy, respectively, modified the ornithine decarboxylase (ODC) activity in the radiosensitive (thymus, spleen) and radioresistant (lung) organs. A nonmonotonic dependence of the ODC activity on the cumulative radiation doses was observed: a decrease in the ODC activity caused by low cumulative radiation doses (after 8 days of exposure) gave way to the level that was close to the control (after 45 and 90 days); after 150 days of exposure, the activity of ODC increased in some organs (spleen and lung). It was suggested that this nonmonotonicity has its origins in the radiation triggering the regulatory systems of the cell homeostasis.

[The catecholaminergic system in the hypothalamus in the chronic gamma irradiation of rats]. / Katekholaminergicheskaia sistema v gipotalamuse pri khronicheskom gamma-obluchenii krys.

Drastic changes in the level of catecholamines (dophamine and noradrenaline) in the central regulatory area of the sympathetic-adrenal system-hypothalamus--caused by continuous gamma irradiation of rats were observed. The irradiation was performed with the doses of 9 to 165 cGy at a rate of 1.1 cGy/day and with the doses of 17 to 315 cGy at a rate of 2.1 cGy/day. Dose dependences of the effect were of a non-monotonic nature. Conclusion was made of a high sensitivity of the sympathetic-adrenal system to the action of chronic low-dose gamma irradiation.

[Effects of single gamma-irradiation on the activity of ornithine decarboxylase in the thymus and pulmonary tissue]. / Vliianie odnokratnogo gama-oblucheniia na aktivnost' ornitindekarboksilazy v timuse i legochnoi tkani.

In studying the dose (0.1-6 Gy) and time (2 h to 180 days) dependence of ornithine decarboxylase activity, it was found that deviations from the control were more pronounced in the thymus than in the pulmonary tissue. The radiation effect was a function of dose and time after irradiation. A nonmonotonous type of the dose-response curve was observed 7 days after irradiation: the radiation effect with a low dose (0.1 Gy) was opposite to that with sublethal doses (1-6 Gy).

[Effects of chronic gamma irradiation on the activity of adenylate cyclase in rat lung tissue]. / Vliianiie khronicheskogo gama-oblucheniia na aktivnost' adenilattsiklazy legochnoi tkani krys.

Different phase changes were observed in adenylate cyclase (AC) activity of pulmonary tissue plasma membranes under chronic gamma-irradiation of rats at a dose-rate of 12.9 cGy/day. Comparison of AC basal activity with the data reported earlier on changes in ornithine decarboxylase activity under similar radiation conditions showed unidirectional changes which indicated that cAMP-dependent processes were possibly involved in radiation modification of ornithine decarboxylase.

[The effect of the dose rate on the development of rat pups under chronic gamma irradiation]. / Vliianie moshchnosti dozy na razvitie krysiat pri khronicheskom gamma-obluchenii.

Chronic exposure of rat pups to gamma radiation, during their intensive growth, at a dose rate of 0.01, 0.11 and 0.5 cGy/day did not affect their development throughout a two-month period of observation. At a dose rate of 12.9 cGy/day rat growth was inhibited during the first 15 days. With further exposure at the same dose rate (over a period of up to five months) the rate of rat pup growth was restored, which indicated the presence of adaptation processes.

[The dynamics of the ornithine decarboxylase activity in chronically gamma-irradiated rats]. / Dinamika aktivnosti ornitindekarboksilazy pri nepreryvnom gamma-obluchenii krys.

Ornithine decarboxylase activity changes in some tissues of chronically gamma-irradiated rats (0.54 cGy/h). The radiation effect is a function of the life span of continuously exposed animals. The data obtained indicate that adaptation is possible, at a metabolic level, with the restricted chronic gamma-irradiation of animals.

[The possible participation of the cAMP system in the activation of ornithine decarboxylase in rat tissues following nonlethal fractionated gamma-irradiation]. / O vozmozhnom uchasti sistemy tsAMF v aktivatsii ornitindekarboksilazy v tkaniakh krys posle neletal'nogo fraktsionirovannogo gamma-oblucheniia.

A study was made of the activity of adenylate cyclase and cAMP-phosphodiesterase in rat thymus and liver various time intervals following nonlethal fractionated gamma-irradiation (2 Gy three times at a week interval). There was a positive correlation between the activity of cAMP metabolism enzymes and the radiation modification of ornithine decarboxylase (ODC) observed before. It is suggested that cAMP system is involved in ODC activity regulation in the exposed tissue.

[Adenylate cyclase activity of the plasma membranes of lung tissue at lengthy periods following non-lethal gamma-irradiation of rats]. / Aktivnost' adenilattsiklazy plasmaticheskikh membran legochnoi tkani v otdalennye sroki posle neletal'nogo gamma-oblucheniia krys.

Basal and stimulated activity of adenylate cyclase (cyclizing ATP-pyrophosphate lyase, E.C. 4.6.1.1., AC) in plasma membranes of pulmonary tissue was being studied during a year after fractionated irradiation of rats (2 GyX3). Basal and hormone-stimulated activity of AC was shown to vary significantly from normal 6 and 12 months after irradiation. The exposed membranes responded differently to AC activation by isoproterenol and F-.

[The stimulating action of low doses of ionizing radiation on glucokinase synthesis in the liver of developing rats]. / Stimuliruiushchee deistvie malykh doz ioniziruiushchei radiatsii na sintez gliukokinazy v pecheni razvivaiushchikhsia krys.

Taking spontaneous glucokinase synthesis as an example the authors showed an increase in the rate of enzymatic differentiation against the insignificantly increased natural radiation background, which might serve as a supporting evidence of the previously obtained data confirming the necessity of the natural radioactive background for the development of mammals.

[Ornithine decarboxylase activity in rat tissues in the late periods after irradiation]. / Ornitindekarboksilaznaia aktivnost' v tkaniakh krys v otdalennye sroki posle oblucheniia.

Ornithine decarboxylase activity in some rat tissues was shown to grow at remote times after gamma irradiation (60Co) with nonlethal doses. The authors suggest that ornithine decarboxylase activity should be used as a biochemical marker of remote effects of ionizing radiation.

[Mechanisms of the disorder of the hormonal regulation of plasma membrane adenylate cyclase in the rat liver during early ontogeny under in vitro irradiation]. / Mekhanizmy narusheniia gormonal'noi reguliatsii adenilattsiklazy plazmaticheskikh membran pecheni krysy v khode rannego ontogeneza v usloviiakh oblucheniia in vitro.

Possible reasons for the previously detected inhibitory effect of gamma-radiation (100-1000 Gy in vitro) on isoproterenol-stimulated activity of adenylate cyclase (AC) of the liver plasma membranes of a 20-day-old rat fetus were investigated. It was discovered that the number of beta-adrenergic receptors was reduced. Analysis of basal and fluorine-stimulated activities of AC attests to the radiation-induced damage to catalytic and N-regulatory proteins. The radiation-induced derangement of membrane lipids, where AC functions, is shown.

[Possible effect of natural radioactivity on the induction of glucokinase synthesis in the liver of developing rats]. / K voprosu o vozmozhnom vliianii estestvennoi radioaktivnosti na induktsiiu sinteza gliukokinazy v pecheni razvivaiushchikhsia krys.

A decrease in the induced synthesis of glucokinase in the liver, at the time of spontaneous appearance of the enzyme, was observed in suckling rats kept for 10 days in a chamber with a decreased (by 10 times) natural radiation background. No changes were noted in the glucokinase synthesis induction after restoration of natural radioactivity by introducing of uranium salts.

[Radiation disorder of enzyme synthesis in the perinatal period of ontogeny]. / Issledovanie radiatsionnogo narusheniia sinteza fermentov v perinatal'nyi period ontogeneza.

A change of enzymatic differentiation in the rat liver during the perinatal developmental period after gamma-irradiation on the 7-9th and 19th days of embryogenesis in doses 0.5, 2 and 6 Gr has been shown on the example of glucose-6-phosphatase (G-6-P-ase) and tyrosine aminotransferase (TAT). The protein-synthesizing machinery was not damaged at these doses. The radiation inhibition of G-6-P-ase synthesis was relieved by the injection of thyroxine. A dependence was shown between the radiation increase of TAT activity and changes in cAMP system (increase of cAMP level, decrease of phosphodiesterase activity, intensification of response of adenylate cyclase complex to biogenic amines). A suggestion is put forward that the radiation damage of the enzymes under study is mediated by a change in the number of hormonal inductors.

[Possible effect of natural background radiation on the development of mammals]. / O vozmozhnom vliianii estestvennogo fona ioniziruiushchei radiatsii na razvitie mlekopitaiushchikh.

The deceleration of the development of young rats during the postnatal ontogenesis under conditions of a low-background chamber (a 10-fold decrease in the natural radiation background) was detected using the criterion of individual growth of the body weight for 10 days of observation. The administration, to the low-background chamber, of uranium salts which restore the natural background (all other experimental conditions being retained) removed the effect observed.

On the mechanism of a radiation-induced change in enzymic differentiation during development.

In experiments on glucose-6-phosphatase and tyrosine aminotransferase it was shown that radiation induces changes in enzymic differentiation in perinatal rat liver. A study was made of the probable reasons for the observed changes. It was shown that the macromolecular system of the protein enzyme synthesis was not damaged by the radiation doses used. The observed decrease in glucose-6-phosphatase activity during late embryogenesis, after pre-irradiation at early organogenesis, is eliminated by administration of exogenous thyroxine. A radiation-induced rise in the tyrosine aminotransferase activity during the perinatal period correlated with the cyclic AMP system status. It is proposed that modification of enzymic differentiation after irradiation results from the change in the amount of inductors.