DNA repair after low doses of ionising radiation

Exposure of mammalian cells to Ionising Radiation (IR) results in an integrated cellular response in which the activation of cell-cycle checkpoints is coordinated with DNA-repair pathways to optimise the removal of potentially cytotoxic or mutagenic DNA lesions. Radiobiological models have usually been based on observations of the cellular response to high doses of IR delivered acutely. This paper discusses how current models can accommodate responses to low dose or low dose-rate irradiation. In particular, the phenomena of low-dose hypersensitivity/induced radioresistance, adaptive responses and bystander effects all require reconsideration of these models. Questions addressed include: whether low doses of IR that are insufficient to activate induced radioresistance invoke DNA-repair responses less efficiently than doses that are above the threshold for this response; whether DNA-repair activity is induced by low (priming) doses of IR that activate the adaptive response; and how DNA-repair status influences the cells' response to bystander signals.