INCREASED EXPRESSION OF CYCLIN B1 MESSENGER-RNA COINCIDES WITH DIMINISHED G(2)-PHASE ARREST IN IRRADIATED HELA-CELLS TREATED WITH STAUROSPORINE OR CAFFEINE

The irradiation of cells results in delayed progression through the G( 2) phase of the cell cycle. Treatment of irradiated HeLa cells with ca ffeine greatly reduces the G(2)-phase delay, while caffeine does not a lter progression of cells through the cell cycle in unirradiated cells . In this report we demonstrate that treatment of HeLa cells with the kinase inhibitor staurosporine, but not with the inhibitor H7, also re sults in a reduction of the G(2)-phase arrest after irradiation. Cell cycle progression in unirradiated cells is unaffected by 4.4 nM (2 ng/ ml) staurosporine, which releases the radiation-induced G(2)-phase arr est. In HeLa cells, the G(2)-phase delay after irradiation in S phase is accompanied by decreased expression of cyclin B1 mRNA. Coincident w ith the reduction in G(2)-phase delay, we observed an increase in cycl in B1 mRNA accumulation in irradiated, staurosporine-treated cells com pared to cells treated with irradiation alone. Caffeine treatment of i rradiated HeLa cells also resulted in an elevation in the levels of cy clin B1 message. These results support the hypothesis that diminished cyclin B1 mRNA levels influence G(2)-phase arrest to some degree. The findings that both staurosporine and caffeine treatments reverse the d epression in cyclin B1 expression suggest that these two compounds may act on a common pathway of cell cycle control in response to radiatio n injury.