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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 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.

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 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.

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.

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 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.

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.

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.

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.

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.

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.

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.

Methodology approach demonstrating a principle importance of mutual increase of damaging action of physical and chemical environmental factors at low doses and intensities was described. A generalize conceptual basis of synergism was suggested which was appropriate both for combined action of ionizing radiation with other agents and for combined action of any other harmful environmental factors. The main idea of the concept described here is in the formation of additional effective damages under combined action due to interaction of sublesions induced by every agent and which are not effective under separate action of each agent employed. Mathematical presentation of this concept allowed to make some new non-trivial conclusions. It was shown theoretically the existence of optimal ratio of damages induced by acting agents under which the highest synergism must be obtained. The effect of synergistic interaction has to be dependent on intensities of agents: the less intensity of one agent used, the small intensity of another factor must be applied for the greatest synergistic effect expression. The test of these consequences was performed for a number of experiments described in this paper. The results presented here have of principle importance for interpretation of the higher effectiveness of low dose and dose rate of ionizing radiation observed in some cases.

The cell lethality and permeability induced in Escherichia coli B/r and Escherichia coli BS-1 by 60Co gamma-ray irradiation, ultrasound and hyperthermia in media containing different concentrations of NaCl have been investigated. It was shown that independently from the nature of damaging factors hypotonic media increase while hypertonic media in certain range of osmolyte concentration decrease sensitivity of cells to action of this factors. It was proposed that discovered phenomenology was caused by salt modification of status of the cell osmotic homeostasis destabilizing by ionizing radiation, ultrasound or hyperthermia and was not related with the system of dark repair of DNA.

The incubation of bacteria Escherichia coli B/r and Escherichia coli Bs-1, preliminarily heated by microwave (frequency 7 GHz) or equal usual heat in water isotonic (0.9%) or hypertonic (10%) solution of sodium chloride resulted in decrease or increase of the cell lethality independently from heating manner. Hypertonic solutions of this compound, as was established, protected the cells against heat damages during the microwave heating less effectively than during thermal heating.

The definitions and various quantitative estimations of synergistic effects are presented. Common regularities of synergistic interaction under combined action of different harmful environmental agents are summarized. Possible mechanisms and mathematical models for prognosis and optimization of the synergistic effect are discussed. The data related with the dependence of synergy on intensity of agents applied are analysed. On this basis, it is concluded the fundamental importance of synergistic interaction at low dose rate of ionizing radiation and/or low intensity of UV light.

The survival of bacterial cells Escherichia coli exposed to sodium nitrate (1-5 M) simultaneously with 60Co gamma rays was shown to be smaller than that expected for independent addition of the effects induced by each of agents applied separately. The synergistic effect was quantitatively estimated by the factor k, which is the ratio of the isoeffective doses on the calculated additive survival curve and the experimental one. The dependencies of k on the exposition of combined action of gamma rays and different NaNO3 solutions (1, 3 and 5 M) are presented. It was demonstrated that the synergistic ratio k was increased with exposure duration increasing. It is suggested that in this case the synergistic effect may be related with the formation of some additional lethal damage due to NaNO3 radiochemical transformation products.

Experimental data on the processes of division and death of haploid and diploid yeast Saccharomyces cerevisiae of wild type and of their radiosensitive mutants exposed under optimal for reproduction conditions to chronic action of gamma-radiation at various dose rates are presented. It is shown that the dependence of the integral division/death process on time was exponential for all the studied strains. With dose rate increasing, the duration of the lag period and the probability of cell inactivation increased, while the multiplication rate decreased. These processes, for equal dose rates, were more expressed for the radiosensitive mutants.

The influence of microwaves and heat on dynamics of heating of samples of intact and inactivated bacteria Escherichia coli and solutions of some basic molecular components of cell was investigated. It was shown that microwaves induce different dynamics of heating of all samples. On the contrary, thermal action induces identical dynamics of heating of all this samples except vegetable oil which was heated more intensively.

Based on the devised calorimetric equipment the values of absorbed doses of UHF-radiation were obtained for laboratory animals. The advantage of application of the specific absorption rate (SAR) and the absorbed dose in comparison with exposure dose and energy flux density was demonstrated. The influence of SAR on lethality in laboratory animals was investigated. It was shown that interspecific sensitivity of laboratory animals was dependent on SAR.

The relative biological efficiency (RBE) of alpha particles for wild-type yeast cells and radiosensitive mutants exposed in stationary and logarithmic stages of growth was compared. A correlation between the RBE of densely ionizing radiation and cell repair capacity was supported for plateau-phase cultures. It was shown for the first time that RBE of alpha particles for cells exposed in logarithmic stage was less than the RBE for stationary cells for all strains studied. For the most mutant cells RBE of alpha particle was closed to unity, i.e. cell radiosensitivity was almost identical for sparsely and densely ionizing radiation. Possible reasons for the observed radiation responses are discussed.

The thermal and specific effects of cm range microwaves on cell systems was investigated. It was shown that cell damage (killing and permeability disturbance) in Escherichia coli B/r, Escherichia coli Bs-1, Saccharomyces cerevisiae and ACE were induced by microwave heating more effectively than by equivalent thermal heat.

The dependence of dose modifying factor after the consecutive thermoradiation actions on dose rate and dose of ionizing radiation as well as on temperature and duration of its application was studied for yeast cells. The results obtained 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.