Search

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 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.

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.)

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.

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.

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 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 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.

Survival curves of S. cerevisiae wild type and rad 50, 51, 52 and 54 mutants in haploid and diploid strains were measured after gamma-ray and alpha-particle irradiation in stationary and exponential phase of growth. The values of RBE of high-LET radiation, defined as the ratio of the mean lethal doses after sparsely and densely ionizing radiations, were determined. A correlation between the RBE of alpha-particles and cell repair capacity was supported for stationary phase cultures. For the first time, it was shown for all strains studied that at exponential phase of growth the RBE of alpha-particle-induced survival was decreased in comparison with that for stationary cells. For most mutant cells RBE was close to unity, i.e. cell radiosensitivity was almost identical for both sparsely and densely ionizing radiation. Possible reasons for the observed radiation responses are discussed.

Diploid cells of the wild-type yeast Saccharomyces cerevisiae, mutants homozygous with respect to rad2 and rad54 loci as well as a double mutant with both these loci in homozygous state were used to demonstrate the previously observed (in other yeast strains) genetic determination of radiosensitivity modification of hypoxic cells by oxygen and electron-affinic compounds. It was shown that both oxygen effect and the effect of hypoxic sensitizers depended on the activity of repair systems. A possible mechanism of participation of postradiation recovery in modification of yeast cell radiosensitivity is discussed.

The combined action of hyperthermia and ionizing radiation on the arrival of isogenic haploid and diploid yeast cells of wild type and rad51 mutant was studied. The experiments demonstrated the essential enhancement of radiosensitivity of diploid wild type cells is hyperthermic conditions. For haploid wild type cells and rad51 mutant cells the enhancement was smaller and negligible respectively. The action of both factors on rad51 homozygous diploid cells was additive. It is established that diploid cells were less thermosensitive than haploid ones. Rad51 mutation does not change these properties. It was concluded that the enhancement of radiosensitivity of cells under hyperthermic conditions depends on cell genotype and may be caused by the reduced capacity of cells to recover the radiation damages inflicted by the both modalities.

A mathematical description of yeast cell recovery after the combined effect of ionizing radiation and hyperthermia is presented. The degree of cell injury was predicted using a calculated irreversible component. A good agreement between the experimental and theoretical results was demonstrated. The possibility of using the proposed model for quantitation of the postirradiation recovery after other combined treatments is discussed.

Modification of cell radiosensitivity was expressed mathematically in terms of known experimental values of oxygen enhancement ratios for different yeast cell strains. It was shown that the parameters used permit to quantitate the dependence of the efficiency of radioprotectors and radiosensitizers upon yeast cell genotype.

The application of a mathematical model of synergism in describing the consecutive combined actions of ionizing radiation and other physical agents has been considered. Using various cell systems it has been shown that the model permits to predict the highest dose modifying factor and conditions in which it can be achieved.

Survival curves were obtained for haploid and diploid yeasts, Saccharomyces cerevisiae, of wild-type strains and radiosensitive mutants exposed to gamma-rays and alpha-particles. A correlation between the values of the relative biological effectiveness (RBE) of high-LET radiation and cell-repair capacity was found. The difference in radiosensitivities of the wild-type diploid strain and homozygous rad mutants incapable of recovery was significantly higher after low-LET radiation than after high-LET radiation. Possible reasons for the observed radiation responses to low- and high-LET exposure of yeast cells with various genotype are discussed.

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.