Inhibition of DNA synthesis in human gliomas by roscovitine

THE early effect of 1-100 mu M roscovitine, a purine analogue and cyclin-de pendent kinase inhibitor, was studied on tissue specimens from eight human malignant gliomas. The tissue was incubated immediately after resection wit h DMEM containing [H-3]methylthymidine plus vehicle alone or the proper con centration of roscovitine for 30-90 min. The DNA synthesis rate was assesse d by measurement of [H-3]methylthymidine incorporation into trichloroacetic acid insoluble material/mg protein/min. In all gliomas, 100 mu M roscoviti ne inhibited DNA synthesis by 71-97% (average 89 +/- 8%, p<0.0001). This in hibitory effect of roscovitine appeared within 30 min of incubation and was concentration dependent. (C) 1999 Lippincott Williams & Wilkins.