DNA Damage Produced by Ionizing Radiation in Mammalian Cells: Identities, Mechanisms of Formation, and Reparability

This chapter provides a framework for understanding the way permanent heritable damage in cellular DNA results from exposure to ionizing radiation. If the processes that occur in the time between the initial radiation energy deposition and the formation of such damage can be described, then rationales can be developed for the modulation of radiation damage. For example, it may be possible to (1) devise a means of differentially modulating the amounts of radiation damage, for instance, in tumor versus normal tissue in radiotherapy, or (2) predict the effects of variations of several parameters on the biological consequences of a radiation dose. It has been concluded that the types and yields of damaged moieties produced in intracellular DNA by low LET ionizing radiation are consistent with the mechanisms of production that involve both OH radical attack and a direct ionization of the macromolecule. At the radiation-dose levels producing one lethal lesion per cell, the amounts of damage produced by ionizing radiation are several orders of magnitude lower than the amounts of damage required for equal kill by other agents. Individual damaged moieties are not biologically significant; they can easily be repaired using the undamaged DNA strand as a template. The lethal lesion produced in cellular DNA is a locally multiply damaged site.