Abstract

The probable mechanism underlying the effect of uridine in potentiating the biological activity of an antileukemic agent, arabinosylcytosine, is described. Only uridine, among other nucleosides, was capable of increasing the radioactivity in spleen after concurrent administration with ara-C-³H. Uridine did not augment the radioactivity in spleen when given in conjunction with other labeled nucleosides. Enzymatic studies with a dialyzed splenic supernatant from BDF₁ mice bearing advanced Leukemia L1210 disclosed that ara-C-³H was phosphorylated with uridine 5'-triphosphate at twice the initial rate as compared to adenosine 5'-triphosphate at equinolar concentrations. The presence of an enzymatic system in spleen was indicated with which uridine 5'-triphosphate is the active phosphate donor. This system is capable of phosphorylating deoxycytidine, but not cytidine. The effects of uridine on the biological activity of ara-C are considered a consequence of increased phosphorylation of ara-C in the presence of uridine 5'-triphosphate.