Role of apoptosis in low-dose hyper-radiosensitivity

S. A. Krueger, M. C. Joiner, M. Weinfeld, E. Piasentin, Brian Marples

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

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 G 1-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.

Original languageEnglish (US)
Pages (from-to)260-267
Number of pages8
JournalRadiation Research
Volume167
Issue number3
DOIs
StatePublished - Mar 1 2007
Externally publishedYes

Fingerprint

Radiation Tolerance
apoptosis
radiation tolerance
Apoptosis
dosage
G2 Phase
cells
interphase
Ionizing Radiation
ionizing radiation
cultured cells
Cell Line
Gastrin-Secreting Cells
DNA Breaks
mitosis
asynchronous transfer mode
Mitosis
Caspase 3
human cell lines
radiation dosage

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Radiology Nuclear Medicine and imaging
  • Biophysics
  • Radiation

Cite this

Krueger, S. A., Joiner, M. C., Weinfeld, M., Piasentin, E., & Marples, B. (2007). Role of apoptosis in low-dose hyper-radiosensitivity. Radiation Research, 167(3), 260-267. https://doi.org/10.1667/RR0776.1

Role of apoptosis in low-dose hyper-radiosensitivity. / Krueger, S. A.; Joiner, M. C.; Weinfeld, M.; Piasentin, E.; Marples, Brian.

In: Radiation Research, Vol. 167, No. 3, 01.03.2007, p. 260-267.

Research output: Contribution to journalArticle

Krueger, SA, Joiner, MC, Weinfeld, M, Piasentin, E & Marples, B 2007, 'Role of apoptosis in low-dose hyper-radiosensitivity', Radiation Research, vol. 167, no. 3, pp. 260-267. https://doi.org/10.1667/RR0776.1
Krueger SA, Joiner MC, Weinfeld M, Piasentin E, Marples B. Role of apoptosis in low-dose hyper-radiosensitivity. Radiation Research. 2007 Mar 1;167(3):260-267. https://doi.org/10.1667/RR0776.1
Krueger, S. A. ; Joiner, M. C. ; Weinfeld, M. ; Piasentin, E. ; Marples, Brian. / Role of apoptosis in low-dose hyper-radiosensitivity. In: Radiation Research. 2007 ; Vol. 167, No. 3. pp. 260-267.
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