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Department of Radiation Oncology [G. D. K., W. G. M., A. M., K. B.], and Department of Pathology and Laboratory Medicine [R. J. M.], University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104
Irradiation of tumor cells results in a G2 delay, which has been postulated to allow DNA repair and cell survival. The G2 delay after irradiation is marked in HeLa and other cells by delayed expression of cyclin B1. To test whether this depression of cyclin B1 contributes to the G2 delay, we induced cyclin B1 expression in irradiated HeLa cells using a dexamethasone-inducible promoter. Induction of cyclin B1 after radiation abrogated the G2 delay by approximately doubling the rate at which the cells reentered mitosis, whereas dexamethasone itself had no effect. However, overexpression of cyclin B1 did not eliminate the G2 delay in irradiated cells. In unirradiated cells, overexpression of cyclin B1 had no effect on cell cycle progression. Confirmation that reduction of cyclin B1 levels would prolong G2 was provided using antisense oligonucleotides to cyclin B1. These results demonstrate that cyclin B1 levels control the length of the G2 delay following irradiation in HeLa cells but do not exclude additional mechanisms controlling the mitotic delay after irradiation.
1 This work was supported by NIH Grants GM 47439, CA 46830, and CA 51149, and American Cancer Society Faculty Research Award (to W. G. M.), and an American Society for Therapeutic Radiology and Oncology Fellowship (to G. D. K.). The flow cytometry facility was supported by the Lucille B. Markey Trust.
2 To whom requests for reprints should be addressed, at Department of Pathology and Laboratory Medicine, John Morgan Building, Room 269, University of Pennsylvania School of Medicine, 3620 Hamilton Walk, Philadelphia, PA 19104.
Received 10/17/96. Accepted 12/20/96.
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