Attenuation of G{sub 2} cell cycle checkpoint control in human tumor cells is associated with increased frequencies of unrejoined chromosome breaks but not increased cytotoxicity following radiation exposure
- and others
The contribution of G{sub 2} cell cycle checkpoint control to ionizing radiation responses was examined in ten human tumor cell lines. Most of the delay in cell cycle progression seen in the first cell cycle following radiation exposure was due to blocks in G{sub 2} and there were large cell line-to-cell line variations in the length of the G{sub 2} block. Longer delays were seen in cell lines that had mutations in p53. There was a highly significant inverse correlation between the length of G{sub 2} delay and the frequency of unrejoined chromosome breaks seen as chromosome terminal deletions in mitosis, and observation that supports the hypothesis that the signal for G{sub 2} delay in mammalian cells is an unrejoined chromosome break. There were also an inverse correlation between the length of G{sub 2} delay and the level of chromosome aneuploidy in each cell line, suggesting that the G{sub 2} and mitotic spindel checkpoints may be linked to each other. Attenuation in G{sub 2} checkpoint control was not associated with alterations in either the frequency of induced chromosome rearrangements or cell survival following radiation exposure suggesting that chromosome rearrangements, the major radiation-induced lethal lesion in tumor cells, form before cells enters G{sub 2}. Thus, agents that act solely to override G{sub 2} arrest should produce little radiosensitization in human tumor cells.
- Research Organization:
- Argonne National Lab. (ANL), Argonne, IL (United States); Chicago Univ., IL (United States). Dept. of Radiation and Cellular Oncology
- Sponsoring Organization:
- USDOE Office of Energy Research, Washington, DC (United States)
- DOE Contract Number:
- FG02-88ER60661; W-31109-ENG-38
- OSTI ID:
- 510590
- Report Number(s):
- ANL/CMB/PP-87206; ON: DE97008369; CNN: Grant CA 42596; Grant CA37435; TRN: 97:014558
- Resource Relation:
- Other Information: PBD: [1997]
- Country of Publication:
- United States
- Language:
- English
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