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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.

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.

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.

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.

Experimental results described earlier showed significantly larger relative biological effectiveness (RBE) values for wild-type diploid cells in comparison with radiosensitive mutants. This aspect was further studied in this paper. Diploid yeast cells were irradiated with gamma rays from (60)Co and alpha particles from (239)Pu in the stationary phase of cell growth. Survival curves and the kinetics of the liquid-holding recovery were measured. When the irradiated cells had completely recovered from potentially lethal damage, they were again exposed to radiation and allowed post-irradiation recovery. The procedure was repeated three times. By use of a quantitative approach - describing the process of recovery as a decrease in the effective radiation dose -, the probability of recovery per unit time and the proportion of irreversibly damaged cells were quantitatively estimated. It was shown that the irreversible fraction of cell injury was increased after repeated exposures to gamma rays, from 0.4 after the first irradiation to 0.7 after the third exposure. The effect was more clearly expressed after exposure to densely ionizing radiation, the corresponding values being 0.5 and 1.0. In contrast, the recovery constant did not depend on the number of repeated irradiations and only slightly depended on radiation quality. It is suggested that the process of recovery from potentially lethal radiation damage itself is not impaired after repeated exposures to both low- and high-LET radiations, and the decrease in the ability of the cell to recover from radiation damage is mainly explained by the increase in the proportion of irreversibly damaged cells., (Copyright © 2014 Elsevier B.V. All rights reserved.)

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., (Copyright © 2014 Elsevier Inc. All rights reserved.)

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.

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.

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.

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.

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.

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.

The potential ability of various physical or chemical agents to enhance their effect when they are applied simultaneously with each other is well-known. The purpose of this study was to adjust a simple mathematical model to describe, optimize and predict a synergistic interaction between fluoride and xylitol on acid production by mutans streptococci. The model suggests that the synergism is caused by the additional effective damage arising from an interaction of sublesions induced by each agent. These sublesions are considered to be ineffective when each agent is used individually. The predictions of the model were verified by comparison with experimental data published by other researchers. It was shown that the model describes the experimental data, predicts the greatest value of the synergistic effect and the condition under which it can be achieved. The synergistic effect appeared to decline with any deviation from the optimal value of the ratio of effective damages produced by each agent alone.

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.

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.

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.

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.

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.

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 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 significance of the UV fluence rate for the synergistic interaction of UV light (254 nm) and heat was demonstrated for the frequency of mitotic recombination in a wild-type diploid yeast of Saccharomyces cerevisiae (strain T1) and for cell inactivation of two wild-type diploid yeast of S. cerevisiae (strains T1, XS800). It was shown for mitotic recombination that a decrease in the intensity of UV exposure results in the necessity of decreasing the temperature at which UV irradiation occurs to provide the same value of the synergistic enhancement ratio. For cell inactivation, there was a specific temperature maximizing the synergistic effect for any constant fluence rate and the temperature range, synergistically increasing the inactivation effect of UV radiation, should be shifted to lower temperatures with a decrease in the fluence rate. To interpret the results observed, a simple mathematical model of the synergistic interaction was applied. The model suggests that the synergistic interaction of UV light and hyperthermia is expected to result from some additional effective damages arising from the interaction of some sublesions induced by both agents. On the basis of data obtained, it was supposed that the synergistic interaction of these factors might take place at small intensities of UV light and temperatures existing in the biosphere. In other words, for a long duration of interaction, which is important for problems of UV light protection and health effects, one can expect a synergistic interaction of this factor with environmental heat or physiological temperatures and thereby an increase in their inactivating and genetic consequences.

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.

Three wild-type diploid yeast strains Saccharomyces ellipsoideus and Saccharomyces cerevisiae and five radiosensitive mutants of S. cerevisiae in the diploid state were irradiated with gamma-rays from 60Co and alpha-particles from 239Pu in the stationary phase of growth. Survival curves and the kinetics of the liquid holding recovery were measured. It was shown that the irreversible component was enhanced for the densely ionizing radiation in comparison to the low-LET radiation while the probability of the recovery was identical for both the low- and high-LET radiations for all the strains investigated. It means that the recovery process itself is not damaged after densely ionizing radiation and the enhanced RBE of the high-LET radiation may be caused by the increased yield of the irreversible damage. A parent diploid strain and all its radiosensitive mutants showed the same probability for recovery from radiation damage. Thus, the mechanism of the enhanced radiosensitivity of the mutant cells might not be related to the damage of the repair systems themselves but with the production of some kind of radiation damage from which cells are incapable to recover.

Cell thermosensitivity of Escherichia coli B/r increases with the cooling rise, especially in hypertonic conditions after heating at 50, 55 and 60 degrees C. A certain relationship is suggested between the observed phenomenon and the osmotic homeostasis system of microorganisms under condition of thermogenic and tonic stress.

Cell survival, synergistic interaction, liquid-holding recovery (LHR) kinetics and inactivation forms after the simultaneous treatment with UV light (254 nm) and various high temperatures were studied in diploid yeast cells Saccharomyces cerevisiae. The synergistic interaction was observed within a certain temperature range in which there was a temperature that maximizes the synergistic effect. The LHR study revealed that both the extent and the rate of recovery greatly decreased with the increase in exposure temperature. A quantitative approach describing the LHR process as a decrease in the effective radiation dose was used to estimate the probability of recovery per unit time and the irreversible component of damage. Using the experimental data obtained and the mathematical model described, it was shown that the irreversible component, i.e. the fraction of cells incapable of recovery, increased with the exposure temperature, whereas the recovery constant, i.e. the probability of recovery per unit time, was independent of the exposure temperature. The increase in the irreversible component was accompanied by an increase in cell death without postirradiation division. It is concluded based on this that the synergistic interaction of UV light radiation and hyperthermia in yeast cells is not related to the impairment of the recovery process itself and that it may be attributed to an increased yield of the irreversible damage.

Cell survival, recovery kinetics and inactivation forms after successive and simultaneous treatments with gamma rays (60Co) and high temperatures were studied in diploid yeast cells capable of recovery. Both the extent and the rate of the recovery were shown to be greatly decreased with increase in the duration of heat treatment (60 degrees C) followed by radiation and with increase in exposure temperature after simultaneous treatment with heat and radiation. A quantitative approach describing the recovery process was used to estimate the probability of recovery per unit time and the irreversible component of damage after the combined treatment with heat and radiation. It was shown that the probability of recovery was independent of the conditions of the treatment with heat and radiation, while the irreversible component gradually increased as a function of the duration of heat treatment (60 degrees C) after sequential treatment with heat and radiation and as a function of the exposure temperature after simultaneous treatment with heat and radiation. The increase in the irreversible component was accompanied by an increase in cell death without postirradiation division. It is concluded on this basis that the synergistic interaction of ionizing radiation and hyperthermia in yeast cells is not related to the impairment of the recovery capacity itself and that it may be attributed to an increased yield of irreversible damage.

The experimental data on radiation reduction of the dynamics of Escherichia coli BS-1 ageing and dying-off with the increase of intensity of chronic exposure to 60Co gamma-Rays in the range of dose rates from 0.1 to 7.6 x 10(2) microGe/h are presented. This phenomenon takes place only under cell irradiation in isotonic and hypotonic suspension medium.

A comparative study of chronic and acute action of ionizing radiation on the processes of aging and dying off of bacterial and yeast cells was carried out. It was ascertained that chronic action of ionizing radiation, 2-10,000 times exceeded the natural background, resulted in slowing down of aging and dying off of both pro- and eukaryotic cells. A single acute irradiation of yeast also resulted in the retardation of dying off of the yeast cells surviving after irradiation. The data is presented demonstrating a great increase in the survival of yeast cells under their repeated irradiation after recovery from potentially lethal radiation.

The influence of 60Co gamma-ray irradiation of low intensity (0.1-0.4, 0.76 x 10(3) microGy/h) on the processes of reproduction, aging and dying off of E. coli B/r and E. coli BS-1 bacteria have been investigated. It was shown that the reproduction of this bacteria strains was not dependent on the dose rate in the range 0.1-0.4 microGy/h. It was shown in comparison with the irradiated E. coli B/r cells dynamics of the aging and dying off of the irradiated E. coli BS-1 is decreased in the process of prolonged (about 190 days) irradiation with a dose rate of 0.76 x 10(3) microGy/h. It is proposed the relationship between the revealed phenomenon of the decrease in the intensity of the irradiated E. coli BS-1 cell aging and dying and the Vavilov-Cerenkov emission.

For mathematical description of synergetic interaction of high environmental temperature and microwaves for animal heating, a simple semi-empirical model was used. In the model, it is suggested that the mechanism of synergistic interaction is caused by the additional effective damages resulting in more higher body temperature increment comparing with that expected for the independent action of each agents. These additional damages are supposed to be produced by the interaction of sublesions induces by each agent and which are ineffective for their separate action. Utilizing the results published for rabbits [15], it was demonstrated that the model describes experimental data, predicts the highest synergistic effect and the condition under which it can be achieved. The data obtained may be useful for the assessment of microwave exposure safe levels.

Various cellular systems have been analysed for synergistic interactions of the simultaneous action of hyperthermia with physical agents including ionizing radiation, ultraviolet light, and ultrasound, and with chemical agents including thio-TEPA and cis-DDP. Some general rules of synergistic interaction were revealed. First, for every constant rate or intensity of exposure to physical factors or concentration of chemical agents, synergy can be observed only within a certain temperature range that is different for various cellular systems. Secondly, within this range, there is a specific temperature that maximizes the synergistic effect. Any deviation of temperature from the optimal one results in a reduction in synergy. Thirdly, the rate of exposure to physical agents or the concentration of chemical agents strongly influences the synergy; i.e. as the dose rate or concentration is reduced, the temperature for maximum synergism decreases. Possible interpretations of the mechanisms responsible for these relationships of synergy are discussed.

The influence of media with different osmotic pressure (NaCl water solution) and chloramphenicol (10 micrograms/ml) on the survival, permeability, and survival curve shape of Escherichia coli B/r and E. coli Bs-1 cells, heated up to 50, 52, and 60 degrees C was investigated. As shown, the survival curve of cells heated up to 60 degrees C in isotonic conditions was characterized by exponential shape, while the survival curves of cells heated up to 50 and 52 degrees C consisted of two components characterizing thermosensitive and thermoresistant parts of cell population. Hypertonic conditions of heat at 52 degrees C decreased cell lethality and permeability. In this case, survival curves were characterized by exponential shape. Chloramphenicol was shown to protect against damaging action of heat at 50 degrees C and not to affect the viability of cells heated at 52 and 60 degrees C. It is proposed that the increase of cell thermoresistance with heat dose elevation at 50 and 52 degrees C in isotonic conditions, which is accompanied by the appearance of thermotolerant components on survival curves, may be associated with accommodational cell reactions. The essence of these reactions consists in stabilization of the osmotic cell homeostasis.

Quantitative regularities of dark recovery of wild-type diploid yeast cells of Saccharomyces cerevisiae simultaneously treated with UV-light (254 nm) and high temperatures (53-56 degrees C) were studied. Under this combined action, the constant of recovery, which defines the probability of elimination of the UV-radiation induced damage per unit of time, did not depend on the temperature of irradiation. It was shown that both the irreversible component of cell damage and the number of cells that died without division gradually increased as the temperature of exposure increased. It is concluded, on this basis, that the mechanism of synergistic interaction of UV-radiation and hyperthermia is related not to the inhibition of dark recovery itself, but to the increase in the shape of irreversibly damaged cells incapable of recovering from the induced damage.

Quantitative regularities of recovery of wild-type diploid yeast cells irradiated with gamma-rays (60Co) simultaneously with exposure to high temperatures were studied. It was shown that in conditions of such a combined action the constant of recovery did not depend on the temperature at which the irradiation was carried out. However, with an increase of acting temperature an augmentation in the portion of irreversible component was registered. The analysis of cell inactivation revealed that the augmentation of the irreversible component was accompanied by a continuous increase of cell killing without any postirradiation division after which cells are incapable of recovery. The reproductive death was mainly exerted after ionizing radiation applied alone while in conditions of simultaneous thermoradiation action the interphase killing (cell death without division) predominated. It is concluded on this base that the mechanism of synergistic interaction of ionizing radiation and hyperthermia may be related with cardinal change in mechanisms of cell killing.

A synergistic interaction of hyperthermia with ionizing or UV light (254 nm) radiation was analyzed in experiments with yeast cells. For a fixed dose rate of radiation, the synergism was shown to be observed only within a definite temperature range (40-45 degrees C), inside of which there was an optimal temperature to achieve the highest synergism. The effectiveness of the synergistic interaction was smaller for haploid cells than for diploid cells. Experimental data from diploid yeast cells evidenced the significance of the exposure rate in the synergistic interaction of heat combined with ionizing or ultraviolet radiation. The data show that the less is the intensity of radiation, the lower is the temperature that should be used to provide some definite, or highest, synergistic interaction with the radiation. To demonstrate the significance of this rule for other cellular systems, the results of other authors published for bacterial spores and mammalian cells are discussed. Calculations from these results have confirmed the revealed relationship between the dose rate and the exposure temperature. On this basis, it is inferred that synergism may take place at small intensities of harmful environmental factors existing in the biosphere. Hence, any assessment of the health or environmental risks should take into account synergistic interactions between harmful agents.

Thermogenic effectiveness of electromagnetic irradiation (EMI) of UHF range (7 GHz) in the dependence on intensity (10-100 mW/cm2) and environmental temperature was studied in experiments with rabbits. Synergistic interaction of EMI and high ambient temperature was established. The existence of optimal EMI and high ambient temperature was established. The existence of optimal EMI intensity at which the synergy was maximal was shown. It is concluded that this interaction should be taken into account for hygienic standardization of nonionizing EMI.

In experiments with wild-type diploid yeast cells of Saccharomyces cerevisiae, the synergistic interaction of ultraviolet (UV) light (wavelength, 254 nm) and heat (45--60 degrees C) was studied both for mutagenic and inactivation effects. Simultaneous hyperthermia and UV light treatments increase the frequency of UV-induced mitotic intergenic recombination (crossing-over) and cell inactivation. The enhancing effect was a function of UV light fluence rate. It is concluded that the effect of hyperthermia on low fluence UV or high fluence UV irradiation results in comparable effects on survival and mitotic recombination suggesting similar modulation by hyperthermia of the effects induced by UV at different fluence rates. The interpretation of the data obtained was carried out within the widely accepted point of view considering the synergistic effects as a result of repair ability damage.

A comparative study of the relative biological effectiveness (RBE) of alpha-particles 249Pu for reproductive and interphase forms of killing of haploid and diploid yeast cells of wild-type and their radiosensitive mutants has been carried out. The correlation between the RBE of alpha-particles and cell repair capacity was confirmed for reproductive death: it was the highest for diploid cells, smaller for haploid cells and the smallest for their radiosensitive mutants. To achieve the interphase cell killing much higher irradiation doses were used after which cells were incapable of liquid-holding recovery during the storing of exposed cells in non-nutrient media at 30 degrees C. The RBE values for this form of killing were significantly lower in comparison with reproductive death. These data are an additional argument supporting the point of view that the RBE of densely ionizing radiation is determined not merely by physical processes of energy absorption as it is traditionally believed but also by ability of cells to recover from DNA damages inflicted by ionizing radiation.

The new data confirming the relations between RBE and recovery of cells are presented. The quantitative evaluation of the contribution of potentially lethal and sublethal damage recovery in radiosensitivity of cells of various origin after exposure to low- and high-LET ionizing radiation was carried out. The conclusion about the greater contribution of potentially lethal damage recovery in the magnitude of RBE in comparison with sublethal damage recovery was made.

A new mathematical model for the synergistic interaction of lesions produced by ultraviolet (UV) light and high temperature has been proposed. The model suggests that synergism is expected from the additional lethal lesions arising from the interaction of sublesions induced by both agents. These sublesions are considered noneffective after each agent is taken alone. The model predicts the dependence of the synergistic interaction on the ratio of lethal lesions produced by each agent applied, the greatest value of the synergistic effect as well as the conditions under which it can be achieved, and the dependence of synergistic effect on UV light fluence rate. These predictions of the model have been tested for the simultaneous combined action of UV light (wavelength 254 nm) and heat (45-57.5 degrees C) on two strains of wild-type diploid yeast cells of Saccharomyces cerevisiae. The theory appears to be appropriate and the conclusions valid.

The possibility of applying the mathematical model of synergism, developed earlier for description of combined effects in cell system, to the description of synergism on organisms level was developed. The model describes data on combined action of ionising radiation and other harmful environmental agents on survival and cancerogenesis in laboratory animals and human beings.

A study was made of the influence of media with different osmotic pressure on cell survival and on optic density of supernatants from Escherichia coli B/r and E. coli Bs-1 cell suspensions heated under different pH values of media. Hyperthermia induced cell death accompanied with the loss of optically active (lambda = 260 nm) material. Both cell damage effects were increased in acid and alkaline conditions, compared to neutral condition of heating. Hypertonic media results in a decrease in thermic cell death and loss of cell substances. Under this condition, the protection influence of high osmotic pressure was seen to increase significantly in acid and alkaline conditions of heating, compared to neutral condition. It has been proposed that a higher thermal damage of microorganisms in acid and alkaline beating conditions and protection influence of hypertonic media, especially expressed in acid and alkaline medium, is caused to a great extent by the status of osmotic cell homeostasis.

The inactivation of wild-type yeast Saccharomyces cerevisiae was studied after simultaneous treatment with ultrasound and hyperthermia. A temperature range was established within which ultrasound and hyperthermia exert a synergistic action. The effect was shown to depend on ultrasound intensity and the temperature at which the treatment takes place. The temperature range enhancing the ultrasound effect shifted forward higher temperature with increasing ultrasound intensity. For every intensity value, an optimal temperature exists at which the synergetic effect is maximum. The biophysical interpretation of the results obtained is based on the assumption that synergism is due to an additional lethal damage, which arises from the interaction of some sub-lesions induced by both agents. These sublesions are considered non-lethal if the agents are applied separately.

The influence of NaCl water solutions and glycerine hypertonic concentration on the survival of bacteria Escherichia coli B/r heated with different values of heat drop was investigated. It was shown that the transfer of cell suspensions from isotonic conditions to media with raised osmotic pressure, preliminarily heated up to 60 degrees C, and the following heating at this temperature inhibited differences in cell sensitivity to heating at different heat drop. Unlike, it was found that the transfer of cell suspensions from isotonic conditions to hypertonic media before and after heating at 60 degrees C increased differences in resistance of these microorganisms to heating at different heat drop. It is proposed that different resistance of bacteria to damaging action of hyperthermia at different heat drop, and a modified influence of hypertonic solutions on these differences may be due to heat induced destabilization of cell osmotic homeostasis. The extent of expression of this destabilization may be determined by a quantitative ratio of osmotic pressure values in the cell-suspension medium system in particular temperature and tonic environmental conditions.

Synergistic effects of simultaneous application of ultraviolet (UV) light and hyperthermia on survival and recombination of diploid yeast cells were studied. For both test-systems the dependence of the synergistic interaction on UV light fluence rate and exposure temperature was revealed: the temperature range synergistically increasing the action of UV light is shifted towards low temperature values with decreasing of UV light fluence rate. For cell survival, the dependence of the synergistic enhancement ratio on the exposure temperature passes through a maximum. A possible qualitative interpretation of these results is discussed.

The inactivation of diploid yeast cells of Saccharomyces cerevisiae was studied after simultaneous treatment of ultrasound and hyperthermia. The existence of a definite temperature range was proved within which a synergistic interaction was determined. An optimal temperature that maximized the synergy could be identified. A simple mathematical model of synergistic interaction of damages produced by ultrasound and high temperature has been proposed. The model suggests that synergism is expected from the additional lethal damage arising from the interaction of sub-lesions induced by both agents. The model allows quantitative analysis of the combined action of two agents used to be performed, and predicts the greatest value of the synergistic effect and conditions under which it can be achieved.

The analysis of synergistic interaction of cisplatin of various concentrations and high temperature on Chinese hamster fibroblasts was performed using a mathematical model. To calculate the synergistic interaction some survival curves obtained after separate and simultaneous combined actions of these agents reported elsewhere have been used. A good agreement between experimental data and the mathematical model prognosis was provided. For a constant temperature, synergism was observed only within a certain range of cisplatin concentration. The highest value of synergism was shifted towards a lower concentration with a decrease in the temperature, at which the combined treatment was carried out. Possible practical utilization of this rule in radiation therapy, medical and food sterilization, and ecology are discussed.

The influence of media with different osmotic pressure (NaCl water solutions) on survival and permeability of Escherichia coli B/r and Escherichia coli Bs-1 cells heated up to 50, 52 and 60 degrees C was investigated. Hypotonic media increased, while hypertonic media, within a certain range of sodium chloride concentrations, decreased the damaging action of heating independently of the temperature. The effectiveness of thermoprotection was seen to increase, and the range of osmolyte concentrations, at which the highest effect of protection takes place, to move markedly towards higher concentrations of NaCl with increase in heating temperature. A certain relationship is suggested between the observed phenomenon and the osmotic homeostasis system of microorganisms under condition of thermogenic and tonic stress.