Attenuation of G{sub 2}-phase cell cycle checkpoint control is associated with increased frequencies of unrejoined chromosome breaks in human tumor cells
- Argonne National Lab., IL (United States)
- Univ. of Chicago, IL (United States)
To test the hypothesis that attenuation in G{sub 2}-phase check-point control leads to elevated frequencies of unrejoined chromosome breaks in mitosis, the relationship between G{sub 2}-phase cell cycle checkpoint control and unrejoined chromosome break frequencies after radiation exposure was examined in cells of 10 human tumor cell lines: 8 squamous cell carcinoma cell lines and 2 lymphoblastoid cell lines. Most of the delay in progression through the cell cycle seen in the first cell cycle after radiation exposure in these cell lines was due to blocks in G{sub 2} phase, and there were large cell line-dependent variations in the length of the G{sub 2}-phase block. There was a highly significant inverse correlation between the length of G{sub 2}-phase delay after radiation exposure and the frequency of induced unrejoined chromosome breaks seen as chromosome terminal deletions in mitosis. This observation supports the hypothesis that the signal for G{sub 2}-phase delay in mammalian cells is an unrejoined chromosome breaks seen as chromosome terminal deletions in mitosis. This observation supports the hypothesis that the signal for G{sub 2}-phase delay in mammalian cells is an unrejoined chromosome break and that attenuation of G{sub 2}-phase checkpoint control allows cells with unrejoined breaks to progress into mitosis. Attenuation in G{sub 2}-phase checkpoint control was not associated with alterations in the frequency of induced chromosome rearrangements, suggesting that most chromosome rearrangements develop prior to G{sub 2} phase, and there was no significant relationship between the length of G{sub 2}-phase delay and inherent radiation sensitivity, suggesting that unrejoined chromosome breaks are not the primary toxic lesion induced by radiation in mammalian cells. 23 refs., 2 figs., 1 tab.
- Research Organization:
- Argonne National Lab. (ANL), Argonne, IL (United States)
- DOE Contract Number:
- W-31109-ENG-38; FG02-88ER60661
- OSTI ID:
- 381016
- Journal Information:
- Radiation Research, Vol. 146, Issue 2; Other Information: PBD: Aug 1996
- Country of Publication:
- United States
- Language:
- English
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