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06:47
One-step Protocol for Evaluation of the Mode of Radiation-induced Clonogenic Cell Death by Fluorescence Microscopy
Published on: October 23, 2017
Role of apoptosis in low-dose hyper-radiosensitivity.
S A Krueger1, M C Joiner, M Weinfeld
1Department of Radiation Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, Michigan 48201, USA.
Radiation Research
|February 24, 2007
Summary
Low-dose hyper-radiosensitivity, an enhanced cell sensitivity to low radiation doses, is linked to apoptosis. This radiosensitivity is associated with G2-phase cells failing to arrest DNA damage progression before mitosis.
Area of Science:
- Radiobiology
- Cell Biology
- Molecular Oncology
Background:
- Low-dose hyper-radiosensitivity (LHDR) describes enhanced cell sensitivity to low doses of ionizing radiation.
- The precise mechanism of cell killing in LHDR remains poorly understood.
- Apoptosis, or programmed cell death, is a key factor in radiation-induced cell killing.
Purpose of the Study:
- To investigate the relationship between apoptosis and LHDR.
- To explore the role of cell cycle progression in LHDR.
- To test the hypothesis that LHDR involves the failure of DNA repair processes in G2-phase cells.
Main Methods:
- Caspase 3 activation assays were used to measure apoptosis.
- Clonogenic survival experiments assessed radiation sensitivity.
- Cell populations were enriched for specific cell cycle phases (G1) to study their role.
Main Results:
- A direct correlation was found between elevated apoptosis and LHDR in multiple mammalian and human cell lines.
- Enriching cell populations with G1-phase cells abolished the enhanced low-dose apoptosis.
- These findings support the association of LHDR with the radioresponse of G2-phase cells.
Conclusions:
- LHDR is associated with increased apoptosis following low-dose radiation exposure.
- The radioresponse of G2-phase cells is critical for LHDR.
- LHDR may result from the failure of ATM-dependent repair mechanisms to arrest G2 cells with unrepaired DNA damage.
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