Some general regularities of synergistic interaction of hyperthermia with various physical and chemical inactivating agents

Various cellular systems have been analysed for synergistic interactions of the simultaneous action of hyperthermia with physical agents including ionizing radiation, ultraviolet light, and ultrasound, and with chemical agents including thio-TEPA and cis-DDP. Some general rules of synergistic interaction were revealed. First, for every constant rate or intensity of exposure to physical factors or concentration of chemical agents, synergy can be observed only within a certain temperature range that is different for various cellular systems. Secondly, within this range, there is a specific temperature that maximizes the synergistic effect. Any deviation of temperature from the optimal one results in a reduction in synergy. Thirdly, the rate of exposure to physical agents or the concentration of chemical agents strongly influences the synergy; i.e. as the dose rate or concentration is reduced, the temperature for maximum synergism decreases. Possible interpretations of the mechanisms responsible for these relationships of synergy are discussed.