Mathematical description of synergistic interaction of hyperthermia and ionizing radiation.

A simple mathematical model of simultaneous combined action of ionizing radiation and hyperthermia has been proposed. The model suggests that the synergistic interaction of ionizing radiation and hyperthermia is expected to result from the additional lethal damage arising from the interaction of sublesions induced by both agents. These sublesions are considered nonlethal after each agent taken alone. The model was applied to the quantitative analysis of the simultaneous action of hyperthermia and ionizing radiation. It predicts the dependence of synergistic interaction of the ratio of lethal events produced by every agent used, as well as the maximal value of the synergistic effect, conditions at which the maximal interactive effect can be achieved, and the dependence of synergistic effect on dose rate. The predictions of the model have been tested with four experimental data sets reported in the literature. The theory appears to be appropriate and the conclusions valid.

[Use of dose parameters of UHF irradiation in the interpretation of lethal effects in laboratory animals]. / Ispol'zovanie dozovykh kharakteristik SVCh-vozdeistviia pri interpretatsii letal'nykh éffektov u laboratornykh zhivotnykh.

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.

[A mathematical description of the synergism in the simultaneous cytotoxic action of chemical agents and hyperthermia]. / Matematicheskoe opisanie sinergizma odnovremennogo tsitotoksicheskogo deistviia khimicheskikh agentov i gipertermii.

Applicability of mathematical model to the description and prognosis of cytotoxicity of tris(1-aziridinyl)-phosphine sulfide (thio-TEPA) and cis-diamminedichloroplatinum (cis-DDP) at various temperatures was tested for the inactivation of clone-forming ability of hamster cells and murine fibrosarcoma. The model suggests that the synergistic interaction of chemical agent and hyperthermia may result from additional lethal damages arising from the interaction of sublesions induced by both the agents. The model allows a quantitative analysis of the combined action of the used agents and predicts the maximum value of the synergistic effect and the conditions under which this effect can be achieved.

[The limit of the modifiability of cellular radiosensitivity in sequential exposure to ionizing radiation and physical factors of a nonionizing nature]. / Predel modifitsiruemosti radiochuvstvitel'nosti kletok pri posledovatel'nom vozdeistvii ioniziruiushchego izlucheniia i fizicheskikh faktorov neioniziruiushchei prirody.

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.

[Mathematical description of the successive action of ionizing radiation and hyperthermia on mammalian cells]. / Matematicheskoe opisanie posledovatel'nogo deistviia ioniziruiushchego izlucheniia i gipertermii na kletki mlekopitaiushchikh.

A previously proposed mathematical model for the description of the effects of simultaneous action of hyperthermia and ionizing radiation was used to predict the successive treatment of these agents. The model suggests that the synergistic effect of combined action of ionizing radiation and hyperthermia is caused by additional lethal damages 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 was tested against experimental data reported by other authors. The applicability of the proposed model was demonstrated to predict the dose modifying factor and the limited modification of mammalian cell radiosensitivity by hyperthermia as well as to reveal a more effective sequence of these agents.

[[Analysis of synergistic effects during thermoradiation exposure of bacteriophage T4 and Bacillus subtilis spores]. / Analiz éffekta sinergizma pri termoradiatsionnom vozdeistvii na bakteriofag T4 i spory Bacillus subtilis.

Experimental data are interpreted in terms of a half-empiric model of synergism obtained for bacteriophage T4 and Bacillus subtilis spores exposed to ionizing radiation of different dose rates at elevated temperatures. The model permits to optimize the ratio of both factors for effective sterilization.

[Quantitative description of a change in radiosensitivity]. / Kolichestvennoe opisanie modifikatsii radiochuvstvitel'nosti.

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.

[Mathematical model of the combined effects of ionizing radiation and hyperthermia on mammalian cells]. / Matematicheskoe opisanie éffektovv odnovremennogo deistviia ioniziruiushchei radiatsii i gipertermii na kletki mlekopitaiushchikh

A previously proposed mathematical model for the depiction of the effects of combined ionizing radiation and hyperthermia on yeast cells of different species was applied to the description of experimental data on mammalian cells. The model suggests that the synergistic effect of combined ionizing radiation and hyperthermia is caused by additional lethal damages arising from the interaction of "sublesions" induced by both agents. These "sublesions" are not lethal after the action of these agents, each taken alone. It has been shown that the thermal enhancement ratios are strongly determined by the ratios of radiation and hyperthermia-induced lethal damages. The model predicts that the maximal synergistic effect after a separate action of these modalities will be achieved if the former agent induces a greater part of lethal damages as compared to the latter one. It has been shown that the model depicts quantitatively the synergism of the simultaneous action of the agents used for Chinese hamster cells and predicts the maximal value of the synergistic effect, conditions under which it can be achieved and the dependence of the synergistic effect on the do se rate.

Photoreactivation of damage induced by ionizing radiation in yeast cells.

Experimental data on photoreactivation of damage induced by ionizing radiation in yeast cells are presented. The value of photoreactivation was found to be the highest for the following conditions predicted by us as optimum ones: large volume of irradiated suspension, hypoxia and high energy sparsely ionizing radiation. A comparison of data for yeast and bacterial cells shows that Cerenkov emission from ionizing radiation may produce photoreactivated pyrimidine dimers in both prokaryotic and eukaryotic cell systems.

[Mathematical model of yeast cell recovery after combined exposure to ionizing radiation and hyperthermia]. / Matematicheskoe opisanie vosstanovleniia drozhzhevykh kletok posle kombinirovannogo vozdeistviia ioniziruiushchego izlucheniia i gipertermii.

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.

[Mathematical model of a simultaneous combined effect of ionizing radiation and hyperthermia]. / Matematicheskaia model' odnovremennogo kombinirovannogo vozdeistviia ioniziruiushchei radiatsii i gipertermii.

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.

Estimation of the contribution of ionization and excitation to the lethal effect of ionizing radiation.

A simple theoretical model is proposed for estimating the differential contribution of ionization and excitation to the lethal effect of ionizing radiation. Numerical results were obtained on the basis of published experimental data on the ability of bacterial cells Escherichia coli to undergo photoreactivation of radiation-induced damage. It was shown that inactivation by excitation may be highly significant for UV-hypersensitive cells capable of photoreactivation; inactivation by excitation increased with the energy of ionizing radiation and the volume of irradiated suspensions. The data are in qualitative agreement with the assumption of a possible contribution of the UV-component of Cerenkov radiation to the formation of excitations responsible for the lethal effect and the phenomenon of photoreactivation after ionizing radiation. Some predictions from the model are discussed.

[Combined action of UV light and alpha particles on yeast cells of different genotypes]. / Kombinirovannoe deistvie UF-sveta i al'fa-chastits na drozhzhevye kletki ralichnykh genotipov.

Combined action of ultraviolet (UV) light and alpha-particles on yeast cells of different genotypes has been studied. Under combined action, after small doses of UV-light the oscillated changes of cell survival were registered for wild-type cells independent of the ploidy and the sequence of application of radiations. Additive effect of high doses of UV-light and ionizing radiation was expressed for strains incapable of the recovery of damages induced by ionizing radiation. For yeast cells possessing such a capability, the synergistic interaction of damages inflicted by high doses of UV-light and alpha-particles was noted. Possible reasons of the observed cell responses are discussed.

Combined action of ultrasound and ionizing radiation on yeast cells.

This communication reports the observation of synergistic relationships between ultrasound and gamma-irradiation of stationary phase cultures of Saccharomyces 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 + gamma-ray)-exposure in comparison with gamma-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.

[Hypophyseal-adrenocortical system reaction to the prolonged action of low doses of selenomethionine-75Se that form during internal contamination]. / Reaktsiia gipofizarno-adrenkortikal'noi sistemy na dlitel'noe vozdeistvie malykh doz, formiruiushchikhsia pri vnutrennem zarazhenii selenometi-oninom-75Se.

A method of radiometry in vivo was applied to study the regularities attending distribution of the absorbed dose and its formation in the course of one year after the administration of 0.033 muCu/g of selenomethionine-75Se to rats, as well as the functional condition of the adaptive hypophysis-adrenal glands system by the determination of plasma corticosterone. A high tropicity of this preparation to the endocrine system organs was demonstrated. Intensification of the functional activity of the adaptive system was indicated by an increase of the blood plasma corticosterone concentration following the administration of a, radioactive preparation and its statistically significant increase (in comparison with control) 3, 6, and 10 months from the beginning of the experiment. The action of acute stress (histamine and formalin) 10 months after the administration of selenomethionine-75Se caused no sharp elevation of the plasma corticosterone concentration characteristic of control rats, this indicating an extreme strain of the hypophysis-adrenal gland system and its incapacity to respond to additional loads. It is supposed that analysis of functional condition of the adaptive system could serve as the key in the assessment of the biological effect of low radiation doses.