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1 March 2007 Role of Apoptosis in Low-Dose Hyper-radiosensitivity
S. A. Krueger, M. C. Joiner, M. Weinfeld, E. Piasentin, B. Marples
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Krueger, S. A., Joiner, M. C., Weinfeld, M., Piasentin, E. and Marples, B. Role of Apoptosis in Low-Dose Hyper-radiosensitivity. Radiat. Res. 167, 260–267 (2007).

Little is known about the mode of cell killing associated with low-dose hyper-radiosensitivity, the radiation response that describes the enhanced sensitivity of cells to small doses of ionizing radiation. Using a technique that measures the activation of caspase 3, we have established a relationship between apoptosis detected 24 h after low-dose radiation exposure and low-dose hyper-radiosensitivity in four mammalian cell lines (T98G, U373, MR4 and 3.7 cells) and two normal human lymphoblastoid cell lines. The existence of low-dose hyper-radiosensitivity in clonogenic survival experiments was found to be associated with an elevated level of apoptosis after low-dose exposures, corroborating earlier observations (Enns et al., Mol. Cancer Res. 2, 557–566, 2004). We also show that enriching populations of MR4 and V79 cells with G1-phase cells, to minimize the numbers of G2-phase cells, abolished the enhanced low-dose apoptosis. These cell-cycle enrichment experiments strengthen the reported association between low-dose hyper-sensitivity and the radioresponse of G2-phase cells. These data are consistent with our current hypothesis to explain low-dose hyper-radiosensitivity, namely that the enhanced sensitivity of cells to low doses of ionizing radiation reflects the failure of ATM-dependent repair processes to fully arrest the progression of damaged G2-phase cells harboring unrepaired DNA breaks entering mitosis.

S. A. Krueger, M. C. Joiner, M. Weinfeld, E. Piasentin, and B. Marples "Role of Apoptosis in Low-Dose Hyper-radiosensitivity," Radiation Research 167(3), 260-267, (1 March 2007).
Received: 26 July 2006; Accepted: 1 November 2006; Published: 1 March 2007
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