Synergistic Interaction and Cell Responses to Environmental Factors

For a quantitative description of variety cell responses to ionising radiation, a mathematical model is suggested. In contrast to the conventional point of view that the relative biological effectiveness (RBE) of densely ionising radiation is determined only by physical characteristics of radiation, this book presents extensive experimental data demonstrating the importance of cell recovery ability in the RBE manifestation. The most impressive data obtained was mostly for diploid mutant cells at the log-stage of growth, in which the RBE was close to unity. It was also shown that the recovery process itself was not damaged after exposure to high-LET radiation, as well as the enhanced RBE values due to the increased yield of irreversible radiation damage from which cells were incapable of recovering. A novel direction in the study of radioprotecting and radiosensitising action of chemical compounds is also discussed and confirmed in the book. A new conception for the mechanism of synergy is suggested, in accordance with the synergy due to the formation of additional effective damages resulting from the interaction of sublesions. These sublesions are supposed to be non-effective when each agent is applied separately. This concept led to the development of original mathematical models of synergy, which is reviewed by the authors. The model predicts a number of general rules of interaction, the condition under which the highest synergy can be achieved, its value, and the dependence of synergy on the intensity of agents applied. Validation of the model was also verified for various physical and chemical factors, biological objects and end points. The theory appears to be appropriate and the conclusions valid.