ATTENUATION OF G(2)-PHASE CELL-CYCLE CHECKPOINT CONTROL IS ASSOCIATEDWITH INCREASED FREQUENCIES OF UNREJOINED CHROMOSOME BREAKS IN HUMAN TUMOR-CELLS

To test the hypothesis that attenuation in G(2)-phase checkpoint contr ol leads to elevated frequencies of unrejoined chromosome breaks in mi tosis, the relationship between G(2)-phase cell cycle checkpoint contr ol and unrejoined chromosome break frequencies after radiation exposur e was examined in cells of 10 human tumor cell lines: 8 squamous cell carcinoma cell lines and 2 lymphoblastoid cell lines, Most of the dela y in progression through the cell cycle seen in the first cell cycle a fter radiation exposure in these cell lines was due to blocks in G(2) phase, and there were large cell line-dependent variations in the leng th of the G(2)-phase block. There was a highly significant inverse cor relation between the length of G(2)-phase delay after radiation exposu re and the frequency of induced unrejoined chromosome breaks seen as c hromosome terminal deletions in mitosis. This observation supports the hypothesis that the signal for G(2)-phase delay in mammalian cells is an unrejoined chromosome break and that attenuation of G(2)-phase che ckpoint control allows cells with unrejoined breaks to progress into m itosis, Attenuation in G(2)-phase checkpoint control was not associate d with alterations in the frequency of induced chromosome rearrangemen ts, suggesting that most chromosome rearrangements develop prior to G( 2) phase, and there was no significant relationship between the length of G(2)-phase delay and inherent radiation sensitivity, suggesting th at unrejoined chromosome breaks are not the primary toxic lesion induc ed by radiation in mammalian cells. (C) 1996 by Radiation Research Soc iety.