General patterns of synergistic and antagonistic interactions in radiobiology

Abstract

Currently multimodal therapy is widely used for treatment of chronic diseases including cancer. The joint use of ionizing or onionizing radiation with hyperthermia or chemotherapeutic agents increases the effectiveness of the treatment. A response of living things to combination treatment may be synergistic, additive or antagonistic. The study is aimed to examine the common regularities of synergistic and antagonistic effects development following exposure of biological objects to various factors. The article presents analysis of experimental data received by the authors of the paper and the data published by other teams. It has been found that therapeutic effects of the same factors do not depend on the objects under study, it depends on the agents parameters: a dose rate, intensity, degree of heating (temperature), concentration of chemotherapeutic agents, etc. The common regularities of synergistic interactions are: 1) synergistic effect is maximum, if the agents act simultaneously, it depends on the ratio of injuries induced by each agent; 2) the optimal correlation between influencing factors provides the maximum synergistic effect; 3) in order to maintain maximum synergistic or antagonistic effects interaction, it is necessary to reduce or to increase the intensity of one of the agents and proportionally to increase or to reduce the intensity of the second agent. The combined effects of hyperthermia and glycerol on bacterial cells are considered as an example of the antagonistic effect. Exposure to different concentrations of sodium chloride, NaCl, in combination with ionizing radiation, or ultrasound, or hyperthermia forms a stable antagonistic effect. Both glycerol and NaCl are osmotic substances and their negative effects can be attenuated by means that stabilize the osmotic homeostasis system. Yeast cells shown the synergistic interaction of ultraviolet light and hyperthermia then it began smoothly passed into antagonistic interaction as the temperature load decreased and the parameters of the influencing factors deviated from the optimal. At the same time, the antagonistic effects are also characterized by the optimal ratio of doses of the agents used, at which the observed effect has the maximum value. The conclusion is made about the commonality of the main regularities of the manifestation of the effects of synergy and antagonism at the interaction of factors of different nature regardless of the biological object, which is subjected to combined influence.