Low-dose hypersensitivity: Current status and possible mechanisms

Michael C. Joiner, Brian Marples, Philippe Lambin, Susan C. Short, Ingela Turesson

Research output: Contribution to journalArticle

411 Scopus citations

Abstract

Purpose: To retain cell viability, mammalian cells can increase damage repair 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 the phenomenon in which cells die from excessive sensitivity to small single doses of ionizing radiation but remain more resistant (per unit dose) to larger single doses. In this paper, we propose possible mechanisms to explain this phenomenon based on our data accumulated over the last decade and a review 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-extrapolating the cell survival response from higher doses. As the dose is increased above about 30 cGy, there is increased radioresistance (IRR) until at doses beyond about 1 Gy, radioresistance is maximal, and the cell survival follows the usual downward-bending curve with increasing dose. The precise operational 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 triggering faster or more efficient DNA repair or (2) causes changes in DNA structure 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.

Original languageEnglish (US)
Pages (from-to)379-389
Number of pages11
JournalInternational Journal of Radiation Oncology Biology Physics
Volume49
Issue number2
DOIs
StatePublished - Feb 1 2001

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Keywords

  • Hypersensitivity
  • Induced radioresistance
  • Radiation

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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