Effect of Uridine Diphosphoglucose on Levels of 5-Phosphoribosyl Pyrophosphate and Uridine Triphosphate in Murine Tissues

Abstract

The purpose of the present investigation was to determine whether a single bolus intravenous injection (2000 mg/kg) of uridine diphosphoglucose (UDPG) could affect levels of PRPP in a transplanted mammary adenocarcinoma and in liver of CD8FI mice. Six hours following a single intravenous injection of UDPG, 2000 mg/kg, tumor PRPP was lowered to 80 pmol/mg protein, a 53% decrease compared to saline control tumors. Liver was more sensitive than tumor to the 5-phosphoribosyl pyrophosphate (PRPP)-depleting effects of a single bolus intravenous injection of UDPG, since significantly lower levels of PRPP were found in liver, but not in tumor, at doses of 500–1000 mg/kg of UDPG. Maximal depression (30% of saline control) or PRPP occurred in liver 6 hr after intravenous UDPG at 1000–2000 mg/kg. Enhanced levels of UDPG in plasma (half-life less than 10 min) and tumor was detected at 30 min after intravenous UDPG at 2000 mg/kg. There was no detectable increase in endogenous levels of UDPG in liver at this time, probably as a result of rapid metabolism of UDPG by liver. At this same time, a twofold increase in uridine triphosphate (UTP) was measured in liver after intravenously administered UDPG. In contrast, the level of UTP was not increased significantly above control values in tumor. These data suggest the potential use of UDPG to elevate UTP pools in normal tissues in the delayed rescue of cancer chemotherapeutic drugs such as 5-fluorouracil which function as a uridine analogue in these tissues.