Combined action of ultrasound and ionizing radiation on yeast cells

Summary This communication reports the observation of synergistic relationships between ultrasound and gamma-irradiation of stationary phase cultures ofSaccharomyces cerevisiae of different strains. The gamma-ray dose was applied before or after the sound. The extent of synergism depended upon the sequence of application; it was smaller for (US +-ray)-exposure in comparison with (-ray + US)-treatment. The combined action of both modalities had smaller or no synergistic effect for mutant (rad51) yeast cells incapable of recovery. On this basis, it was concluded that possible mechanisms for ultrasound radiosensitization of yeast cells may involve the reduced capacity of cells to recover damages resulted from the combined action and/or the enhanced expression of lethal damage.     

Recovery of yeast cells following the combined action of hyperthermia and ionizing radiation

Consecutive action of elevated temperature (50 degrees C) and gamma-irradiation on yeast cells Saccharomyces cerevisiae was studied. It was shown that yeast cells can recover from lethal thermal and radiation lesions after the combined action of the two factors. The efficiency of recovery does not depend upon the sequence of treatments. Heating (50 degrees C) before or after gamma-irradiation increases the radiation response of yeast when plating the cells on a nutrient agar containing 1.5 M KCl. The synergistic effect decreases with yeast cells kept in water at 28 degrees C before plating. The influence of one factor on the effectiveness of recovery from damages induced by the other was estimated.     

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.     

Membrane effects of ionizing radiation and hyperthermia

Results of numerous studies demonstrate that membranes are important sites of cell damage by both ionizing radiation and hyperthermia. Modification of membrane properties (mainly lipid fluidity) affects the cellular responses to radiation and hyperthermia but former concepts that membrane rigidification sensitizes cells to radiation while membrane fluidization potentiates hyperthermic damage have now been seriously challenged. It seems that the effects of membrane fluidity on cell responses to hyperthermia and radiation are due to an indirect influence on functional membrane proteins. The major role of lipid peroxidation in radiation damage to membranes has also been questioned. The existing evidence makes it unlikely that the interaction between radiation and hyperthermia is determined by the action of both agents on the same membrane components.     

Mathematical model of a simultaneous combined effect of ionizing radiation and hyperthermia

A mathematical model has been proposed suggesting that the synergistic action of a combination of ionizing radiation and hyperthermia is conditioned by additional lethal damages arising from the interaction of "sub-lesions" induced by both agents. The model describes quantitatively the synergism of the combined action of the agents used and predicts the maximal value of the synergistic effect and conditions in which it can be achieved.     

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 action of ionizing radiation on DNA in the presence of quinacrine

Strand breakage of DNA irradiated in solution and in the dry state in the presence of quinacrine was investigated by sedimentation analysis. Determination of single strand breaks in solution combined with binding studies permits to conclude that bound quinacrine protects DNA more effectively than the free compound. In the dry state quinacrine is without detectable effect on both single and double strand break formation, neither under aerobic nor anaerobic conditions.     

The action of ionizing radiation on DNA in the presence of quinacrine

It is shown by UV absorption and absolute fluorescence spectroscopy of solutions containing both DNA and quinacrine that the components experience mutual radio-protection due to scavenging of water radicals. From measurements at different ionic strengths it is inferred that quinacrine bound to DNA is more efficiently protected than the free compound. Furthermore, release of bound quinacrine from DNA is observed at higher doses.     

Effect of the dose rate on the synergism of combined ionizing radiation and hyperthermia

In experiments with yeast cells it was shown that the synergistic effect of a combination of ionizing radiation and hyperthermia is a function of dose rate. It was demonstrated that the temperature at which radiation is delivered should be elevated to obtain the maximum synergistic effect with the increasing dose rate.     

The effect of microwave radiation on the cell genome

Cultured V79 Chinese hamster cells were exposed to continuous radiation, frequency 7.7 GHz, power density 30 mW/cm2 for 15, 30, and 60 min. The parameters investigated were the incorporation of [3H]thymidine and the frequency of chromosome aberrations. Data obtained by 2 methods (the incorporation of [3H]thymidine into DNA and autoradiography) showed that the inhibition of [3H]thymidine incorporation took place by complete prevention of DNA from entering into the S phase. The normal rate of incorporation of [3H]thymidine was recovered within 1 generation cycle of V79 cells. Mutagenic tests performed concurrently showed that even DNA macromolecules were involved in the process. In comparison with the control samples there was a higher frequency of specific chromosome lesions in cells that had been irradiated. Results discussed in this study suggest that microwave radiation causes changes in the synthesis as well as in the structure of DNA molecules.     

The effect of ionizing radiation on the respiration of rat thymocytes

The oligomycin-sensitive component of the rate of oxygen consumption by rat thymocytes increased by 22% after X-irradiation. The postirradiation increase in the thymocyte respiration rate was connected with the impairment of a balance between sodium, potassium and calcium and with the protein synthesis activation, and was independent of lymphokine production by lipoxygenase. Irradiation was ineffective with respect to electron transport in the respiratory chain and electrogenic leakages through the inner membrane of thymocyte mitochondria.     

Recovery of yeast cells after exposure to ionizing radiation and hyperthermia

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.