EARLY INHIBITION OF DNA-SYNTHESIS IN THE DEVELOPING RAT CEREBRAL-CORTEX BY THE PURINE ANALOGS OLOMOUCINE AND ROSCOVITINE

The effects of the cyclin-dependent kinase (CDK) inhibitors olomoucine and roscovitine on DNA synthesis were studied using short time incuba tion (30-90 minutes). Both purine analogues at concentrations from 1-1 00 mu M decreased the DNA synthesis of rat brain cortex in a dose-depe ndent manner and the maximum effect occurred within 30 min of incubati on. Staurosporine, another potent CDK inhibitor did not affect the DNA synthesis in the concentration range 1-250 nM. These results indicate that olomoucine and roscovitine block DNA synthesis by a mechanism in dependent of CDK inhibition. We propose that the cellullar effects of olomuocine and roscovitine on the cell. cycle are at least in part due to this early inhibitory effect on DNA synthesis. (C) 1998 Academic P ress.