[Optimization and Prognosis of Cell Radiosensitivity Enhancement in vitro and in vivo after Sequential Thermoradiactive Action].

Previously developed mathematical model of simultaneous action of two inactivating agents has been adapted and tested to describe the results of sequential action. The possibility of applying the mathematical model to the interpretation and prognosis of the increase in radio-sensitivity of tumor cells as well as mammalian cells after sequential action of two high temperatures or hyperthermia and ionizing radiation is analyzed. The model predicts the value of the thermal enhancement ratio depending on the duration of thermal exposure, its greatest value, and the condition under which it is achieved.

[INCREASE IN CELL RADIOSENSITIVITY AFTER INHIBITION OF CELL ABILITY TO RECOVER FROM POTENTIALLY LETHAL RADIATION DAMAGE].

The paper presents new experimental results demonstrating the recovery of irradiated cells on a nutrient medium, which usually occurs at a delay of cell division. Using the previously proposed method, the contribution of such a recovery in radiation sensitivity of diploid yeast cells of different strains after exposure to ionizing and ultraviolet radiation has been estimated. It is shown that the actual increase in cell radiosensitivity significantly exceeds the expected one in the case of inhibition of the recovery from potentially lethal damage. These data indicate that inhibition of cell ability to recover from potentially lethal radiation damage by exposing the irradiated cells in non-nutritive medium in many cases serve as an indicator of suppression of the overall ability of cells to repair. Experimental data indicating that it is not a universal rule are presented.

[Effects of Intensity of Acting Agents on the Manifestation of Synergistic Interaction].

The universal dependence of the synergistic interaction on the intensity of the acting agents was demonstrated. This dependence is not associated with the biological object, as well as the nature of the physical or chemical agents used in the combined exposures. In all cases, with a decrease in the intensity of one of the agents the intensity of the other factor should be also decreased to ensure the greatest synergistic effect. Such relationship of synergy and the intensity of the acting agents is of interest for radiation safety. This regularity indicates the principal possibility of synergistic interaction of harmful environmental factors actually occurring in the biosphere at their low intensities.

Radiation quality and the shape of dose-effect curves at low doses of ionizing radiation for eukaryotic cells.

To explain different yeast and mammalian cell response to low and high linear energy transfer (LET) radiation in low dose region, the dependence of fine target structure on the stage of cell growth was supposed. Theoretical consideration based on this suggestion was carried out. Results of calculations are qualitatively in agreement with experimental data under assuming that hit-event for both mammalian and yeast cells is a group of ionizations produced by the same ionizing particle. In the dependence of cell cycle phase, sensitive sites (presumable the vulnerable sections of chromosomes) can be located either in periphery of cell nucleus forming a thin layer inside the nucleus or distributed evenly over the whole nucleus. Such rearrangement of the target results in the alteration of the dependence of both survival curve shape and the relative biological effectiveness values on radiation quality.

[Regularities of the highest synergistic interaction display].

The synergistic interaction effects of various physical and chemical environmental factors on cells of different origin are presented. Some general patterns of biological manifestations of synergy are analyzed. It is shown that synergistic interactions may be revealed only within a certain range of acting agents and within this range there is an optimum value at which the greatest effect is observed. Possible mechanisms of these effects and their practical usefulness are discussed.

[Cisplatin influence on: the radiosensitivity and recovery of yeast cells].

The effect of the simultaneous combined action of ionizing radiation and cisplatin on the radiosensitivity and liquid holding recovery (LHR) of diploid yeast cells was studied. It was shown that regardless of the cisplatin concentration (0; 0.002; 0.01; 0.02 g/ml) the radiosensitivity of cells was increased by 1.3 times. The ability of a cell to the LHR was progressively decreased with the increasing cisplatin concentration up to the complete inhibition. It was shown that the LHR of yeast cells after a combined action of ionizing radiation and chemical agents is mainly inhibited due to formation of a greater proportion of irreversible damage. The constant of recovery, characterizing the probability of recovery per a unit of time, was independent on cisplatine concentration.

[On one term (translation of SAR) in the dosimetry of radiofrequency electromagnetic fields].

Uncertainties in the use of some terms in the dosimetry of radiofrequency electromagnetic fields are discussed. We have come to the conclusion that the term conventionally applied in the Russian literature to describe the absorbed energy is an incorrect translation of the international term "Specific Absorption Rate" (SAR). The main error in the Russian term is that the energy rather than the rate is absorbed. More precise Russian definition for this term is suggested by analogy with the dosimetry of ionizing radiation. In this case, the dimension of this parameter remains without any change.

[Estimation of UV light dose concomitant to ionizing irradiation].

A simple approach to the estimation of UV light dose produced by Cerenkov emission and concomitant irradiation of biological objects with ionizing radiation was suggested. The approach was applied to determine the dependencies of UV light dose (equivalent to 254 nm) accompanied 100 Gy of ionizing radiation on the energy of sparsely ionizing radiation and on the volume of the exposed Escherichia coli cells suspension. It was revealed that the relative excitation contribution to the total lethal effect and the value of the UV dose was greatly increased with an increase in the energy of ionizing radiation and the volume of irradiated suspensions. It is concluded that these observations are in agreement with the supposition that Cerenkov emission is responsible for the production of UV light damage and the phenomenon of photoreacrivation observed after ionizing exposure of bacterial and yeast cells hypersensitive to UV light. A possible synergistic interaction of the damages produced by ionizations and excitations as well as a probable participation of UV component of ionizing radiation in the mechanism of radiation hormesis and adaptive response observed after ionizing radiation exposure is discussed.

[Mathematical modeling of synergistic interaction of sequential thermoradiation action on mammalian cells].

Data obtained by other authors for mammalian cells treated by sequential action of ionizing radiation and hyperthermia were used to estimate the dependence of synergistic enhancement ratio on the ratio of damages induced by these agents. Experimental results were described and interpreted by means of the mathematical model of synergism in accordance with which the synergism is expected to result from the additional lethal damage arising from the interaction of sublesions induced by both agents.

Some peculiarities of the sequential action of heat and ionizing radiation on yeast cells.

The dependence of the thermal enhancement ratio after a sequential action of heat and ionizing radiation on the dose and dose rate of ionizing radiation as well as on the temperature and duration of its application was studied for yeast cells. The combined effect of heat and ionizing radiation on cell killing depended on both the sequence of application (i.e. whether heat is applied prior to or following irradiation) and the temperature. The effectiveness of treatment with heat and ionizing radiation was greatly dependent on the duration of heat exposure. For an equal amount of cell killing from heat alone, long action of heat (50 degrees C) was more effective for radiosensitization than a short acute action of high heat (58 degrees C). For heating at 50 degrees C, heating after irradiation produced more radiosensitization than heating before irradiation. However, high heating at 58 degrees C before irradiation gave the same radiosensitization as heating after irradiation. These data confirm similar observations for mammalian cells. The results were interpreted by means of a mathematical model in which the synergistic effect of the sequential application of heat and ionizing radiation results from the additional lethal damage arising from the interaction of sublesions induced by both agents. These sublesions are not lethal after the action of these modalities, each taken alone. The model appears to be appropriate and the conclusions are valid.

[Phenomenon of Escherichia coli viability reactivation during late periods of culture in salt buffer after ionizing irradiation].

The experimental showing, that reactivation viability phenomenon of E. coli B/r bacteria in phosphate buffer takes place only after irradiation under certain dose range of 60Co gamma-ray, induced the death of certain part of viable cell bacteria population, are presented. It was illustrated that intensity of reactivation viability phenomenon of bacteria do not depend on the concentration of viable microorganisms and the presence in suspension medium nutrient material, leaved of irradiated cells. The received data shown that in the base of the phenomenon there are the processes, distinguished from processes of usual cell reproduction, and may be the consequence of radiostimulate influence on the cell physiology, known from literature, as hormesis.

[About the characters of thermoprotection in influence of osmolites on bacteria].

The influence of the length of staying of Escherichia coli B/r cells in hypertonic NaCl solution before heating at 52 and 60 degrees C on the magnitude of salt thermoprotection was investigated. In addition, the dependence of the isotonic and thermoprotective NaCl concentrations on the exposure temperature was investigated. It was shown that the volume of cell osmotic thermoprotection was independent on the length of preliminary staying of microorganisms in hypertonic NaCl solution. It was also shown that the magnitude of isotonic and thermoprotective osmolite concentrations increased with the increase in the exposure temperature. The analysis of the data obtained and published in literature indicates that the compensating mechanism is involved in salt bacteria thermoprotection rather than the dehydratation one.

[The recovery parameters of DNA strand breaks of Ehrlich ascites cells after the combined action of ionizing radiation and hyperthermia].

A mathematical model of DNA strand breaks postirradiation repair and the methodology allowing to differentiate the mechanism of inhibition of DNA strand breaks recovery after combined actions of ionizing radiation and hyperthermia have been described in this paper. Using this model and the results published by other authors for DNA strand breaks of Ehrlich ascites cells, there have been obtained the data showing that the portion of DNA-damages that the cell incapable to recover after consecutive thermoradiation action was risen with an increase in thermal load under insignificant change of repair constant. It means the mechanism of DNA strand breaks recovery inhibition is realized in a greater extent through the formation of irreversible damages but not through the damage of repair process itself.

[The influence of chemical inhibitors of DNA repair on the recovery of mammalian cell damages induced by ionizing radiation].

Using experimental results published by other authors the irreversible component of radiation damage and recovery constant, characterized the probability of recovery of mammalian cells of various origin from radiation damages per unit time, have been calculated. It was shown that the inhibition of postirradiation recovery, displayed in the decreasing of both the rate and the volume of recovery, has occurred due to the increasing in the portion of radiation damages from which the cell is incapable to recover. At the same time the recovery constant was independent on the conditions of combined action in the most cases, being decreasing in small extent only for hydroxyurea and 3-aminobenzamide. It was concluded that the inhibition of recovery is not the main reason of chemical radiosensibilization, but is a quite expected consequence of the increase in the portion of irreversibly damaged cells.

[Animal death after exposure to ultra-high frequency waves in the dependence of power flux density and specific absorption rate].

A comparative analysis and mathematical modeling of laboratory animal sensitivity (mice, rats, rabbits and dogs) to microwave exposure in the dependence of the power flux density (PFD) and the specific absorption rate (SAR) were carried out. The results obtained in our laboratory and some data published by other authors were presented as the dependence of the survival time of various animals during exposure both on PFD and SAR of microwave radiation (0.46; 2.4 and 7 GHz). It is shown that if PFD is used as a dosimetric parameter, the animal sensitivity to nonionizing electromagnetic ultrahigh frequency radiation increased with animal mass. If SAR was used as a dosimetric parameter, the arrangement of animals in accordance with their sensitivity to microwave became quite opposite. Mathematical equations describing the dependence of the survival time of laboratory animals on the duration and the intensity of microwave radiation were obtained. These equations describe the published experimental data and can be used to predict the animal death during the process of microwave irradiation.

[Effect of ionizing irradiation of low intensity on the viability of Escherichia coli bacteria, cultivated in the salt buffer].

The influence of 60Co gamma-ray irradiation of low intensity (0.35 Gy/min) on the viability of Escherichia coli B/r and Escherichia coli BS-1 bacteria cultivated in salt buffer in concentration of 10(8) cell/ml was investigated. It was shown that under the doses induced the cell killing about 60-75%, the irradiated bacteria, like intact cell, were killed during the incubation process, while after the doses induced the cell killing above 99% of cell population, the bacteria viability of the both strains was increased. The increase reaches a certain value on the 2-5 the days of bacterial incubation in this conditions. The nature of observed phenomenology is vague for the present.

[The influence of cyclic heating and cooling on Escherichia coli survival].

Repeated heating and cooling in lethal (2-52 degrees C) and nonlethal (2-37 degrees C) temperature ranges resulted in cell death of Escherichia coli B/r and E. coli B(S-1) suspended in 0.01 M phosphate buffer, pH 7.0 at varying osmotic pressure, but not in cow's milk. The lethal effect increased with the rate of heating and with increasing suspension media tonicity; it may be caused by the temperature destabilization of cellular osmotic homeostasis.

[Prognosis of yeast cells recovery after simultaneous exposure to UV-radiation and hyperthermia].

The results of experimental investigations of survival of diploid yeast cells Saccharomyces cerevisiae (strain XS800) after simultaneous exposure to UV-radiation (254 nm) and hyperthermia (53-57 degrees C) have been described. It was shown that the portion of cells capable of recovery in innutrient medium after the action of these agents decreased with the increasing of temperature under which the irradiation was occurred. Mathematical model taking into account the synergistic interaction was suggested for quantitative prediction of irreversible component after combined actions of these agents. A good correspondence between experimental data and model predictions has been demonstrated. The importance of the results obtained for the interpretation of the synergistic interaction mechanisms are discussed.

[The influence of ionizing radiation of high intensity on the viability of Escherichia coli bacteria, cultivated in the salt buffer without nutrient additions].

The influence of 60Co gamma-ray radiation of high intensity (85 Gy/min) on the viability of E. coli B/r and E. coli BS-1 bacteria, cultivated in salt buffer with the concentration about 10(8) cells/ml, was studied. It was determined that under the doses, which induce about 80% of death of the cells, the irradiated bacteria, just like the intact cells, die during the incubation processes, while under the doses induced the death of cells above 95%, the cells viability of the both strains increases and reaches the constant value by the byhend 2nd-5th days of incubation in these conditions. In the result of the differences of the reactions of the intact and irradiated with different doses of radiation microorganisms on the incubation during their postradiational period in the phosphate buffer we have the fact of the absence of the dependence of the effect from the dose, or the decreasing of the consequences of the radiation under the increasing of the dose of the radiation. The nature of this phenomenology while stays not understood.

Quantitative evaluation of the parameters of bacterial photoreactivation after exposure to ultraviolet light and ionizing radiation.

The purpose was to compare quantitatively the parameters of photoreactivation of an ultraviolet (UV) light hypersensitive strain of Escherichia coli Bs-1 irradiated with UV light and ionizing radiation. In addition, to evaluate the influence of the different physical and chemical factors on the parameters of the photoreactivation kinetics of the bacterial cells exposed to ionizing radiation. Survival curves and kinetics of the photoreactivation were measured in E. coli Bs-1 cells exposed to UV light (254 nm) and ionizing radiations (gamma-rays of 137Cs, gamma-rays of 60Co and 25 MeV pulsed X-rays). A mathematical model describing the process of photoreactivation in terms of a decreasing effective dose was applied to the experimental data obtained here and that published by others to evaluate quantitatively the probability of photoreactivation and the irreversible component of the radiation damage. Both the rate and extent of photoreactivation decreased in the following order of inactivating agents: WUV light, pulsed X-ray beam, gamma-ray of 60Co and gamma-ray of 137Cs. However, the irreversible component of radiation damage increased with the same order of radiations whereas the probability of photoreactivation per unit time was independent of the kind of radiation. After exposure to 6 MeV photons, the parameters of photoreactivation were changed in the presence of caffeine or after irradiation in the presence of the radioprotective agent dithiothreitol. The independence of the probability of photoreactivation on the quality of radiation indicates the cells have the same ability to photoreactivate damage produced by different kinds of radiations and is an additional argument indicating that during ionizing radiation a UV-like damage can be produced. The decrease in the extent and the rate of photoreactivation with radiation quality is explained by the formation of irreversible damage rather than by the impairment of the photorecovery process itself. Chemical and physical factors influencing the relative contribution of ionization and excitation on the ionizing radiation effect could modify both the extent of the photoreactivation and the probability of the recovery per unit time. It is concluded that the mathematical approach used here may be useful to reveal some new relationships between the parameters of photoreactivation.