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.