Is low-dose hyper-radiosensitivity a measure of G2-phase cell radiosensitivity?
Low-dose hyper-radiosensitivity describes a phenomenon by which cells die from excessive sensitivity to small single doses of ionizing radiation below approximately 20-30 cGy. This review describes experimental data that strongly imply that low-dose hyper-radiosensitivity is exclusively associated with the survival response of cells in the G2 phase of the cycle. This G2-centric concept arose when the characteristic cell survival pattern that denotes low-dose hyper-radiosensitivity was not detected in the radiation survival response of cell populations enriched in G1 or S phase cells. In contrast, an extended or exaggerated low-dose hyper-radiosensitivity response was evident from populations selected to contain only G2 phase cells by flow cytometry cell sorting. The historical data that has defined the field of low-dose hyper-radiosensitivity will be considered with respect to the radiation sensitivity of, and cell cycle checkpoints specific to, G2 phase cells. A working model of the putative mechanism of low-dose hyper-radiosensitivity will be presented within this context. 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 early G2 phase checkpoint has been demonstrated to exhibit a dose expression profile that is comparable to the cell-survival pattern that defines low-dose hyper-radiosensitivity and is therefore a likely key regulator of the phenomenon.
Marples
B
B
Department of Radiation Oncology, Karmanos Cancer Institute, Wayne State University, Hudson Webber Building, Room 824, 4100 John R, Detroit, MI 48201-2013, USA. marplesb@kci.wayne.edu
D000818:Animals; D004249:DNA Damage / Q000528:radiation effects; D016195:G2 Phase / Q000502:physiology* / Q000528:radiation effects*; D006801:Humans; D008954:Models, Biological; D011836:Radiation Tolerance / Q000502:physiology*; D015398:Signal Transduction / Q000528:radiation effects