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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.

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A synergistic interaction of hyperthermia with ionizing or UV light (254 nm) radiation was analyzed in experiments with yeast cells. For a fixed dose rate of radiation, the synergism was shown to be observed only within a definite temperature range (40-45 degrees C), inside of which there was an optimal temperature to achieve the highest synergism. The effectiveness of the synergistic interaction was smaller for haploid cells than for diploid cells. Experimental data from diploid yeast cells evidenced the significance of the exposure rate in the synergistic interaction of heat combined with ionizing or ultraviolet radiation. The data show that the less is the intensity of radiation, the lower is the temperature that should be used to provide some definite, or highest, synergistic interaction with the radiation. To demonstrate the significance of this rule for other cellular systems, the results of other authors published for bacterial spores and mammalian cells are discussed. Calculations from these results have confirmed the revealed relationship between the dose rate and the exposure temperature. On this basis, it is inferred that synergism may take place at small intensities of harmful environmental factors existing in the biosphere. Hence, any assessment of the health or environmental risks should take into account synergistic interactions between harmful agents.

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