ABSTRACT
This book originated when it was suggested to me by a publisher that since I had been involved in teaching radiation biology for a number of years, Imight be interested inwriting a text on the subject. To this I naturally replied that there was nothing to be gained fromwriting a radiation biology textbook because there already was one, which was frequently updated [1]. (In fact, there is more than one [2,3].) The suggestion, however, caused me to think around the subject and particularly about the fact that-as have all branches of biomedicine-the radiation sciences have been overtaken and irreversibly transformed by the concepts and technology of molecular biology. An axiom about the effect of ionizing radiation is that the primary target
for cell killing is DNA and the distribution of radiation dose is random, not constrained by pharmacology. The finding that cell killing correlates well with unrepaired double-strand DNA breaks indicated that DNA is the prime target. Results of many recent studies have shown, however, that there are radiation-induced changes in an array of cellular targets. These include signal transduction pathway changes, mitochondrial changes, and apoptotic and cell cycle changes. Some of the changes are in response to DNA damage; however, non-DNA-mediated targets including the cell membrane and mitochondria can be critically involved in cell killing or can be the primary targets. New biological concepts for the molecular radiation oncology era are the possibility to modulate normal tissue response based on the understanding that late radiation injury is the result of chronic persistent inflammatory and cytokine-mediated processes. Almost coincidental with the development of molecular radiobiology,
mechanistic and molecular studies of the effects of low doses of radiation have resulted in radical changes in the perception of radiation effect. Bystander effects occur in non-hit cells as well as in cells where energy has been deposited. Genomic instability, which might be the result of radiation exposure, has been shown to play a role in the development of cancer. Finally, recent studies have shown that radiation-induced changes in gene expression can occur at very low doses and that these may be involved in protective or adaptive responses. These nontargeted effects, which have major implications for dosimetry, treatment planning, and risk assessment, are also discussed in this book.
