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.