Uridine diphosphoglucose (
UDPG) has been shown to have tissue-specific effects that have proved to be of clinical value in the treatment of some liver ailments. In an effort to determine something about the mechanism of action, we investigated the effect of
UDPG on the levels of 5-phosphoribosyl
pyrophosphate (PRPP) and
PRPP synthetase in mouse liver, spleen and transplanted
tumors. Three strains of mice were studied with and without
tumors under various experimental conditions. Balb/c mice were infused with
UDPG intraperitoneally at levels of 0.16 g/kg/day (0.28 mmole) to 1.6 g/kg/day (2.8 mmoles) for 5 days. At the low dose rate the PRPP level in the liver was found to increase 3-fold. A slight increase was noted in the activity of
PRPP synthetase. However, when the
UDPG was infused at a level of 2.8 mmoles/kg/day, the increases in both the
synthetase and PRPP were inhibited. Both CRF1 and CD8 mice were less sensitive to the effects of
UDPG per se. However, the high level of PRPP in the
tumors they carried was greatly affected by the
UDPG infusion. The
tumor-specific inhibition of PRPP suggests that this action might prove to be useful combination
therapy with inhibitors of
purine and
pyrimidine nucleotide synthesis in various rescue regimens.
UDPG was found to enter cells intact before it was cleaved into
glucose phosphate and
UMP. The fact that
UDPG was also found in the membrane fraction suggests that either there is a specific transport mechanism or
UDPG exerts its action via interaction with the cell membrane.