Low-dose hypersensitivity: Current status and possible mechanisms

Purpose: To retain cell viability, mammalian cells can increase damage repa ir in response to excessive radiation-induced injury. The adaptive response to small radiation doses is an example of this induced resistance and has been studied for many years, particularly in human lymphocytes, This review focuses on another manifestation of actively increased resistance that is of potential interest for developing improved radiotherapy, specifically th e phenomenon in which cells die from excessive sensitivity to small single doses of ionizing radiation but remain more resistant (per unit dose) to la rger single doses. In this paper, we propose possible mechanisms to explain this phenomenon based on our data accumulated over the last decade and a r eview of the literature. Conclusion: Typically, most cell lines exhibit hyper-radiosensitivity (HRS) to very low radiation doses (<10 cGy) that is not predicted by back-extrap olating the cell survival response from higher doses. As the dose is increa sed above about 30 cGy, there is increased radioresistance (IRR) until at d oses beyond about 1 Gy, radioresistance is maximal, and the cell survival f ollows the usual downward-bending curve with increasing dose. The precise o perational and activational mechanism of the process is still unclear, but we propose two hypotheses. The greater amount of injury produced by larger doses either (1) is above a putative damage-sensing threshold for triggerin g faster or more efficient DNA repair or (2) causes changes in DNA structur e or organization that facilitates constitutive repair, In both scenarios, this enhanced repair ability is decreased again on a similar time scale to the rate of removal of DNA damage. (C) 2001 Elsevier Science Inc.