INHIBITION OF RIBONUCLEOSIDE METABOLISM IN EHRLICH ASCITES TUMOR CELLS BY PURINE ANALOGUE RIBONUCLEOSIDES

Abstract

Several aspects of the metabolism of inosine and uridine by Ehrlich ascites carcinoma cells in vitro have been found to be inhibited by ribonucleoside derivatives of four purine analogues. The synthesis of both inosine and uridine by intact tumor cells was profoundly inhibited in the presence of 6-methylmercaptopurine ribonucleoside. Also inhibited were inosine and uridine cleavage, and the exchange of isotope between these ribonucleosides and the corresponding C14 labelled bases. These reactions, however, were not inhibited when they took place in broken-cell preparations. Similarly, inosine metabolism in intact cells (but not in broken cells) was profoundly inhibited by three related compounds: the ribonucleosides of the 6-chloro, 6-methylmercapto, and 6-propylmercapto derivatives of 2-aminopurine.