Effect of N1-(2'-tetrahydrofuryl)-5-fluorouracil and 5-fluorouracil on nucleic acid and protein biosyntheses in Ehrlich ascites cells.

Abstract

N1-(2'-Tetrahydrofuryl)-5-fluorouracil (FT-207) is a derivative of 5-fluorouracil (5-FU) and has been accepted as a new chemotherapeutic drug. The inhibitory effects of FT-207 and 5-FU on nucleic acid and protein biosyntheses in Ehrlich ascites cells were compared. Both drugs markedly inhibited the incorporation in vivo of the labeled precursors into nucleic acid and protein. The inhibitory effect of FT-207 on DNA and RNA synthesis lasted for a long period of time. Two hr after administration of 5-FU (250 mug/g body weight), the absolute size of uracil pool of liver increased by at least 50%. However, in an in vitro study, FT-207 at a concentration of 60 mug/ml produced no effect on the incorporation of precursors into DNA and RNA of Ehrlich ascites cells 3 hr incubation. If 5-FU was added to Ehrlich ascites cell suspension simultaneously with [5-3H]uridine, the incorporation of the labeled precursor into RNA increased by 30 to 50%.