The delayed effects of the combined action of hyperthermia and ionizing radiation on yeast cells Saccharomyces cereviciae were investigated and compared with analogous effects of gamma-irradiation alone. It was shown that cells, survived after thermoradiate exposure, as well as cells, survived after gamma-irradiation form different in size colonies. The diminishing of size is accompanied by the increasing of the radiosensitivity of cells from these colonies. No significant difference between the radiosensitivity of the progeny of cells, survived the combined exposure, and the radiosensitivity of the progeny of gamma-irradiated cells was observed. A preposition can be made, that the thermal exposure of yeast cells before gamma-irradiation don't practically influence on the delayed effects. The magnitude of recovery (liquid holding recovery) on progeny of surviving cells is essentially smaller then the magnitude of recovery of irradiated parent culture without dependence on the type of initial exposure: combined action or just gamma-irradiation. This magnitude is correlated with the degree of the parental cell damage.

Studies with rats and white mice demonstrated that combined radiation injury (CRI) comes to reducing protease activity in small intestine tissues. In liver tissue the activity of cathepsine D increased under the action of new enterosorbent--clay of Kaluga deposit ("CKD"). In blood serum of the damaged animals the amount of histogenic toxins--middle mass molecules (MMM) and oligopeptides decreased after "CKD" administration. An effective fixation and withdrawal of bacteria from the bowl of the affected animals took place. The survival level of mice in 30 days after CRI comprised 20% as compared with 60% in the case of "CK D" administration. It is supposed that the increase of survival after "CKD" administration is the result of enhancement of macrophage detoxification in liver, determined on the increase of activity of cathepsine D (lysosomal protease), elimination of MMM and normalization of gut microflora.

The dependence of synergy enhancement ratio 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 published before 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.

The Chernobyl accident and other radiation-related accidents are characterized by involvement of a variety of hazardous factors which aggravate the damaging action of ionizing radiation. The synergetic effect of different agents can exacerbate anticipated consequences of an accident. This review attempts to establish regularities in biological responses to the combined effect of ionizing radiation and other hazardous environmental factors of chemical, biological or physical nature. A series of universal features accounting for responses of different cell-systems, animals and people have been identified. These features do not depend on the nature of an agent used in conjunction with ionizing radiation or test-system and biological object under study. A conclusion is made regarding a possible significance of the synergetic effect resulting from interaction of various agents for enhancing consequences of the Chernobyl accident.

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.

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.

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 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.