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Differential Effect of Ionizing Radiation on the Expression of Cyclin A and Cyclin B in Hela Cells¹

Departments of Pathology [R. J. M., H. B. Z.] and Radiation Oncology [W. G. M.], University of Pennsylvania, Philadelphia, PA 19104

Ionizing radiation induces a G₂ delay in eukaryotic cells. Since mitotic cyclins are required to trigger the transition from G₂ into the through mitosis, we chose to investigate their expression after irradiation in Hela cells. In normally cycling Hela cells, both cyclin A and B mRNA and protein levels rise dramatically in G₂/M and rapidly fall coincident with the completion of mitosis. The rise of cyclin A mRNA at the S/G₂ boundary slightly precedes that of cyclin B mRNA. Although the peaks of expression of each of these molecules overlap, cyclin A mRNA and protein diminish before cyclin B. After irradiation in S, cyclin A mRNA and protein levels rose with the same kinetics as in the controls, but ultimately exceeded the levels seen in the control population. Cyclin A mRNA and protein levels remained high throughout the G₂ delay induced by irradiation. In contrast, cyclin B mRNA and protein levels did not rise as the irradiated cells entered G₂/M. Only later, before the irradiated cells exited from G₂/M, did levels of cyclin B reach the levels seen in the unirradiated controls. The decreased amount of cyclin B mRNA and protein was inversely proportional to the dose of radiation. These data indicate that irradiation that results in a G₂ delay appears to block cells at a point after production of cyclin A but before cyclin B can be fully expressed and that cells do not exit from the delay until cyclin B is again expressed. Thus, cyclin A and cyclin B expression respond differentially to radiation, with cyclin A rising at the same time as the control and to even higher levels than that seen in the controls, whereas cyclin B shows a temporal delay in expression.

¹ This work was supported by an American Cancer Society Junior Faculty Research Award (R. J. M.), a Clinical Oncology Cancer Development Award (W. G. M.), and Grants CA 46830, 51149, and GM47439.

² To whom requests for reprints should be addressed, at Room 520, Clinical Research Building, University of Pennsylvania, Philadelphia, PA 19104.

Received 7/22/92. Accepted 12/21/92.

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