Enhancement of ribonucleoside synthesis in Ehrlich ascites tumor cells by arsenate and iodoacetate.

Abstract

Ehrlich ascites tumor ceils in vitro synthesize ribonucleosides, which appear mainly in the incubation medium, by the transfer of ribose from a donor ribonucleoside to an acceptor base. In the present study, it was found that the rates of synthesis of inosine and uridine in this system were markedly enhanced in the presence of arsenate or iodoacetate. The exchange of isotope between extracellular inosine and hypoxanthine-8-C14was similarly enhanced by arsenate, but the more rapid exchange between uridine and uracil-2-C14was unaffected. Arsenate did not cause changes in the rates of uridine breakdown that would account for the enhanced rate of nucleoside synthesis and did not promote the release of nucleoside-synthesizing enzymes from the tumor cells into the incubation medium. Because lactate formation during the uridine-supported synthesis of inosine was markedly inhibited by arsenate and iodoacetate, the increase in ribonucleoside synthesis appears to be indirect and to be related to inhibition of ribose phosphate catabolism.