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5-Phenethyl-2'-deoxyuridine (PEUdR) augmented 5-fluoro-2'-deoxyuridine (FUdR) cytotoxicity up to 100-fold in several human gastric cancer cell lines. PEUdR also potentiated 5-fluorouracil (5-FU) cytotoxicity about 5-fold. In contrast, PEUdR reversed 5-fluorouridine (FUR) cytotoxicity in all cell lines studied. PEUdR was not cytotoxic up to 200 microM. PEUdR inhibited the incorporation of [3H]thymidine and [14C]uridine into acid-insoluble fractions, and also inhibited uptake of [3H]thymidine into KATO III cells. Thus, PEUdR inhibits pyrimidine nucleoside transport and salvage enzymes, which potentiates the cytotoxicity of FUdR and reverses the effect of FUR in human gastric cancer cells. These results may contribute to more effective cancer chemotherapy with FUdR and 5-FU.
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