Early inhibition of DNA synthesis in the developing rat cerebral cortex by the purine analogues olomoucine and roscovitine.
The effects of the cyclin-dependent kinase (CDK) inhibitors olomoucine and roscovitine on DNA synthesis were studied using short time incubation (30-90 minutes). Both purine analogues at concentrations from 1-100 microM decreased the DNA synthesis of rat brain cortex in a dose-dependent manner and the maximum effect occurred within 30 min of incubation. 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 independent of CDK inhibition. We propose that the cellular effects of olomuocine and roscovitine on the cell cycle are at least in part due to this early inhibitory effect on DNA synthesis.
Yakisich
J S
JS
Clinical Research Center, Karolinska Institute, Novum, Sweden.
Sidén
A
A
Idoyaga Vargas
V
V
Eneroth
P
P
Cruz
M
M
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D004247:DNA / Q000096:biosynthesis*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005047:Etoposide / Q000494:pharmacology; D007701:Kinetin; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology*; D011687:Purines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077546:Roscovitine; D019311:Staurosporine / Q000494:pharmacology; D013936:Thymidine / Q000031:analogs & derivatives / Q000378:metabolism; D014316:Tritium
D004791:Enzyme Inhibitors; D019384:Nucleic Acid Synthesis Inhibitors; D011687:Purines; D000077546:Roscovitine; D014316:Tritium; C090046:olomoucine; D005047:Etoposide; D004247:DNA; C012439:methylthymidine; D018844:Cyclin-Dependent Kinases; D019311:Staurosporine; D007701:Kinetin; D013936:Thymidine