Increased cyclin E level in retinoblastoma cells during programmed cell death

Camptothecin (an inhibitor of topoisomerase I) and etoposide and amsacrine (inhibitors of topoisomerase II) both capable of triggering programmed cell death in Y79 cells, induced a remarkable dose-dependent increase in the le vel of cyclin E in these cells. Camptothecin was found to be the most effec tive compound. The effect was not observed when the cells were treated with other inducers of programmed cell death (C-2-ceramide, sodium butyrate, in terleukin-1 beta and tumor necrosis factor), all of which do not damage DNA . The effect, which was completely prevented by inhibitors of macromolecula r synthesis, occurred after a lag phase (12 hrs.) and increased concurrentl y with the rise in programmed cell death (PCD), reaching a maximum after 36 hrs. of incubation, when a large percentage of cells (95%) showed clear PC D signals. We suggest that cyclin E takes part in the final stage of progra mmed cell death which is induced by topoisomerase inhibitors in Y79 cells.