Actions of radiation on living cells in the "post-bystander" era

Over the past 20 years there has been increasing evidence that cells and the progeny of cells surviving a dose of ionizing radiation can exhibit a wide range of effects inconsistent with the level of dose received. Recently, the cause of these delayed effects has been ascribed to so-called bystander effects, occurring in cells not directly hit by an ionizing track, but which are influenced by signals from irradiated cells. These effects are not necessarily deleterious, although most of the literature deals with adverse delayed effects. What is important to consider is what, if anything, these effects mean for what is still the central dogma of radiobiology and radiation protection, i.e., that DNA double-strand breaks are the primary radiation-induced lesion that can be quantifiably related to received dose, and which determine the probability that a cancer will result from a radiation exposure. In this chapter we review the history of radiation biology which led to the DNA paradigm. We explore the issues and the evidence which are now challenging the view that dose deposition in DNA is all important. We conclude that in the low-dose region, the primary determinant of radiation exposure outcome is the genetic and epigenetic background of the individual and not the dose. This effectively dissociates dose from effect as a quantitative relationship, but it does not necessarily mean that the effect is unrelated to DNA damage somewhere in the system.