Theoretical Conception of Synergistic Interactions

An increase in the overall biological effect under the combined action of ionizing radiation with another inactivating agent can be explained in two ways. One is the supposition that synergism may attribute to a reduced cellular capacity of damn-ge repair after the combined action. The other is the hypothesis that synergism may be related to an additional lethal or potentially lethal damage that arises from the interaction of sublesions induced by both agents. These sublesions ave considered to be in-effective when each agent is applied separately. Based on this hypothesis, a simple mathematical model was established. The model can predict the greatest value of the synergistic effect, and the dependence of synergy on the intensity of agents applied, as well. This paper deals with the model validation and the peculiarity of simultaneous action of various factors with radiation on biological systems such as bacteriophage, bacterial spores, yeast and mammalian cells. The common rules of the synergism aye as follows. (1) For any constant rate of exposure, the synergy can be observed only within a certain temperature range. The temperature range which synergistically increases the effects of radiation is shifted to the lower temperature fer thermosensitive objects. Inside this range, there is a specific temperature that maximizes the synergistic effect. (2) A decrease in the exposure rate results in a decrease of this specific temperature to achieve the greatest synergy and vice versa. For a constant temperature at which the irradiation occurs, synergy can be observed within a certain dose rate range. Inside this range an optimal intensity of the physical agent may be indicated, which maximizes the synergy. As the exposure temperature reduces, the optimal intensity decreases and vice versa. (3) The recovery rate after combined action is decelerated due to an increased number of irreversible damages. The probability of recovery is independent of the exposure temperature for yeast cells irradiated with ionizing or UV radiation. Chemical inhibitors of cell recovery act through the formation of irreversible damage but not via damaging the recovery process itself.