[The manifestation of synergy during simultaneous thermochemical action on yeast cells].

In order to obtain new fundamental knowledge, patterns of manifestation of synergy have been studied after simultaneous combined action of hyperthermia (47.5-60 degrees C) with anti-tumor agents (cyclophosphamide, cisplatin) on the survival of yeast cells. To calculate the efficiency of the synergistic interaction, the dependence of cell survival on the duration of exposure at separate and simultaneous action of chemical agents and hyperthermia was used. We have found that there is a certain temperature range within which there is a synergistic enhancement of anticancer drugs and high temperature effects. Any deviation from the optimum values of the temperature results in a decrease in synergy. The possible mechanism of the revealed patterns is discussed.

[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 prognosis of the portion of irreversible radiation damages after simultaneous action of hyperthermia and ionizing radiation on yeast cells].

The results of experimental research of diploid yeasts cells survival after simultaneous action of hyperthermia and ionizing radiation (60Co) have been described. It was shown that the cell ability to liquid holding recovery decreased with an increase in the temperature, at which the exposure was carried out. due to the increase in the irreversible component determining the relative part of radiation damage which cells are incapable to recover. To predict theoretically the relative part of irreversible radiation damage after combined action, the mathematical model was suggested taking into account the synergistic interaction of agents. Good correlation between experimental results and model prediction was demonstrated. The importance of the results obtained for the interpretation of the mechanism of synergistic interaction of various factors is discussed.

[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.

[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.

[Dark recovery of diploid yeast cells after simultaneous exposure to UV-irradiation and hyperthermia]. / Temnovoe vosstanovlenie diploidnykh drozhzhevykh kletok posle odnovremennogo vozdeistviia UF-izlucheniia i gipertermii.

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.

[Mathematical description of synergistic interactions of environment temperature and microwaves for animal warming]. / Matematicheskoe opisanie sinergicheskogo vzaimodeistviia temperatury okruzhaiushchei sredy i mikrovoli pri nagreve zhivotnykh.

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.

[Recovery of yeast cells after exposure to ionizing radiation and hyperthermia]. / Vosstanovlenie drozhzhevykh kletok posle vozdeistviia ioniziruiushchego izlucheniia i gipertermii.

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.

[Dependence of synergism of the combined effect of ultrasound and hyperthermia upon intensity of ultrasound]. / Zavisimost' sinergizma odnovremennogo deistviia ul'trazvuka i gipertermii ot intensivnosti ul'trazvuka.

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.

Mathematical description of combined action of ultrasound and hyperthermia on yeast cells.

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.

Fluence rate as a determinant of synergistic interaction under simultaneous action of UV light and mild heat in Saccharomyces cerevisiae.

In experiments with wild-type diploid yeast cells of Saccharomyces cerevisiae, the synergistic lethal action of a simultaneous application of ultraviolet (UV) light (wavelength, 254 nm) and mild heat (45-57.5 degrees C) was studied. It was shown that, at any fixed UV light intensity, the synergistic effect occurred within the given temperature interval. The optimal temperature to achieve the greatest synergistic effect may be shown for every fluence rate examined. The correlation between the optimal temperature that maximized the synergy and UV light intensity was estimated: this temperature shifted towards higher temperature values with an increasing fluence rate. A possible interpretation of this effect is based on the supposition that the mechanism of the synergistic effect is related to additional lethal damage produced by the interaction of sublesions induced by each agent. These sublesions are supposed to be non-lethal when each agent is applied separately.