Increased Expression of Cyclin B1 mRNA Coincides with Diminished${\rm G}_{2}\text{-Phase}$ Arrest in Irradiated HeLa Cells Treated with Staurosporine or Caffeine

The irradiation of cells results in delayed progression through the G₂ phase of the cell cycle. Treatment of irradiated HeLa cells with caffeine greatly reduces the G₂-phase delay, while caffeine does not alter progression of cells through the cell cycle in un-irradiated cells. In this report we demonstrate that treatment of HeLa cells with the kinase inhibitor staurosporine, but not with the inhibitor H7, also results in a reduction of the G₂-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 G₂-phase arrest. In HeLa cells, the G₂-phase delay after irradiation in S phase is accompanied by decreased expression of cyclin B1 mRNA. Coincident with the reduction in G₂-phase delay, we observed an increase in cyclin B1 mRNA accumulation in irradiated, staurosporine-treated cells compared to cells treated with irradiation alone. Caffeine treatment of irradiated HeLa cells also resulted in an elevation in the levels of cyclin B1 message. These results support the hypothesis that diminished cyclin B1 mRNA levels influence G₂-phase arrest to some degree. The findings that both staurosporine and caffeine treatments reverse the depression in cyclin B1 expression suggest that these two compounds may act on a common pathway of cell cycle control in response to radiation injury.