Low-dose hyper-radiosensitivity

A consequence of ineffective cell cycle arrest of radiation-damaged G2-phase cells

Brian Marples, B. G. Wouters, S. J. Collis, A. J. Chalmers, M. C. Joiner

Research output: Contribution to journalReview article

172 Citations (Scopus)

Abstract

This review highlights the phenomenon of low-dose hyperradiosensitivity (HRS), an effect in which cells die from excessive sensitivity to small single doses of ionizing radiation but become more resistant (per unit dose) to larger single doses. Established and new data pertaining to HRS are discussed with respect to its possible underlying molecular mechanisms. To explain HRS, a three-component model is proposed that consists of damage recognition, signal transduction and damage repair. The foundation of the model is a rapidly occurring dose-dependent pre-mitotic cell cycle checkpoint that is specific to cells irradiated in the G2 phase. This checkpoint exhibits a dose expression profile that is identical to the cell survival pattern that characterizes HRS and is probably the key control element of low-dose radiosensitivity. This premise is strengthened by the recent observation coupling low-dose radiosensitivity of G2-phase cells directly to HRS. The putative role of known damage response factors such as ATM, PARP, H2AX, 53BP1 and HDAC4 is also included within the framework of the HRS model.

Original languageEnglish (US)
Pages (from-to)247-255
Number of pages9
JournalRadiation Research
Volume161
Issue number3
DOIs
StatePublished - Mar 1 2004
Externally publishedYes

Fingerprint

G2 Phase
Radiation Tolerance
radiation tolerance
Cell Cycle Checkpoints
Radiation
dosage
cycles
radiation
cells
Ionizing Radiation
Signal Transduction
Cell Survival
damage
Observation
asynchronous transfer mode
ionizing radiation
sensitivity
profiles

ASJC Scopus subject areas

  • Radiation
  • Biophysics
  • Radiology Nuclear Medicine and imaging

Cite this

Low-dose hyper-radiosensitivity : A consequence of ineffective cell cycle arrest of radiation-damaged G2-phase cells. / Marples, Brian; Wouters, B. G.; Collis, S. J.; Chalmers, A. J.; Joiner, M. C.

In: Radiation Research, Vol. 161, No. 3, 01.03.2004, p. 247-255.

Research output: Contribution to journalReview article

Marples, Brian ; Wouters, B. G. ; Collis, S. J. ; Chalmers, A. J. ; Joiner, M. C. / Low-dose hyper-radiosensitivity : A consequence of ineffective cell cycle arrest of radiation-damaged G2-phase cells. In: Radiation Research. 2004 ; Vol. 161, No. 3. pp. 247-255.
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