Induced radioresistance: an overview and historical perspective.

There is now considerable evidence that cellular radioprotective mechanisms exist that are upregulated in response to exposure to small doses of ionizing radiation and other DNA-damaging agents. There appear to be two ways in which these 'induced' mechanisms operate: either protecting against a subsequent exposure to radiation that may be substantially larger than the initial 'conditioning' dose, or by influencing the response to single doses so that small acute radiation exposures, or exposures at very low dose-rates, are more effective per unit dose than larger exposures above a threshold where the induced radioprotection is triggered. These effects have been well documented in studies with yeast, bacteria, protozoa, algae, higher plant cells, insect cells, mammalian and human cells in vitro, and studies on animal models in vivo. Both increased and decreased levels of some cytoplasmic and nuclear proteins, and increased expression of some genes, may occur shortly after exposure to DNA-damaging agents, within a few hours or even minutes. This would be rapid enough to explain the phenomenon of induced radioresistance, although the precise mechanism by which this occurs, whether it is through repair, cell-cycle control, or some other process, remains yet undefined.