Low-Dose Hyper-radiosensitivity: A Consequence of Ineffective Cell Cycle Arrest of Radiation-Damaged G2-Phase Cells (original) (raw)
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1 March 2004 Low-Dose Hyper-radiosensitivity: A Consequence of Ineffective Cell Cycle Arrest of Radiation-Damaged G2-Phase Cells
B. Marples,B. G. Wouters,S. J. Collis,A. J. Chalmers,M. C. Joiner
Author Affiliations +
B. Marples,1,* B. G. Wouters,2 S. J. Collis,3 A. J. Chalmers,4 M. C. Joiner1
1aKarmanos Cancer Institute, Wayne State University, Detroit, Michigan
2bMAASTRO Laboratory, University of Maastricht, Maastricht, The Netherlands
3cThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Department of Radiation Oncology, B
4dRadiotherapy Department, The Royal Marsden NHS Trust, Fulham Road, London, United Kingdom
*Address for correspondence: Radiation Biology Group, Karmanos Cancer Institute, Hudson Webber Building, Room 824, 4100 John R., Detroit, MI 48201-2013; marplesb@kci.wayne.edu
Abstract
Marples, B., Wouters, B. G., Collis, S. J., Chalmers, A. J. and Joiner, M. C. Low-Dose Hyper-radiosensitivity: A Consequence of Ineffective Cell Cycle Arrest of Radiation-Damaged G2-Phase Cells. Radiat. Res. 161, 247–255 (2004).
This review highlights the phenomenon of low-dose hyper- radiosensitivity (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 G2phase. 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.
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B. Marples, B. G. Wouters, S. J. Collis, A. J. Chalmers, and M. C. Joiner "Low-Dose Hyper-radiosensitivity: A Consequence of Ineffective Cell Cycle Arrest of Radiation-Damaged G2-Phase Cells," Radiation Research 161(3), 247-255, (1 March 2004). https://doi.org/10.1667/RR3130
Received: 11 September 2003; Accepted: 1 October 2003; Published: 1 March 2004
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