Early Inhibition of DNA Synthesis in the Developing Rat Cerebral Cortex by the Purine Analogues Olomoucine and Roscovitine

• Published in: Biochemical and biophysical research communications 1998-02, Vol.243 (3), p.674-677
• Main Authors: Yakisich, J.Sebastian, Sidén, Åke, Vargas, Victor Idoyaga, Eneroth, Peter, Cruz, Mabel
• Format: Article
• Language: English
• Subjects: Animals; Cell Cycle - drug effects; Cerebral Cortex - drug effects; Cerebral Cortex - growth & development; Cerebral Cortex - metabolism; Cyclin-Dependent Kinases - antagonists & inhibitors; DNA - biosynthesis; Enzyme Inhibitors - pharmacology; Etoposide - pharmacology; Kinetin; Medicin och hälsovetenskap; Nucleic Acid Synthesis Inhibitors - pharmacology; Purines - pharmacology; Rats; Rats, Sprague-Dawley; Roscovitine; Staurosporine - pharmacology; Thymidine - analogs & derivatives; Thymidine - metabolism; Tritium
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.1998.8157

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 μM 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 cellullar effects of olomuocine and roscovitine on the cell cycle are at least in part due to this early inhibitory effect on DNA synthesis.