• The Korean Journal of Pharmacology
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• v.26 no.1
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• pp.91-100
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• 1990

The benzylacycoluridines (BAU and BBAU) are potent and specific inhibitors of uridine phosphorylase (UrdPase). In contrast to the report that benzylacyclouridines potentiated 5-fluoro-2'-deoxyuridine (FdUrd) cytotoxicity against human solid tumor cells (Cancer Res., 44:1852, 1984), continuous exposure of mouse lymphoma L5178Y cells, to FdURd, 5-fluorouridine (FUrd), 5'-deoxy-5-fluorouridine (5'-dFUrd), or 5-fluorouracil (FUra) showed no potentiation of cytotoxicity by benzylacyclouridines. In fact, under the conditions employed, benzylacycoluridines protected the cells from the cytotoxicity of FdUrd, FUrd, or 5'-dFUrd, but not FUra in a dose dependent manner. Intraperitoneal coadministration of BAU or BBAU and a 5-fluorinated pyrimidine (i.e., FdUrd, FUrd, or FUra), to mice bearing L5178Y cells also did not significantly increase the life span compared to those treated with the antimetabolites alone. Anabolism of these nucleosides through the sequential action of UrdPase and orotate phosphoribosyltransferase (OPRTase), inhibition of nucleoside transport by benzylacyclouridines, or both could be responsible for the ineffectiveness of UrdPase inhibitors to potentiate the antineoplastic activity of fluoropvrimidines in L5178Y cells.