Effect of 2-beta-D-ribofuranosylthiazole-4-carboxamide on uptake of nucleosides by cultured L1210 cells.

2-beta-D-Ribofuranosylthiazole-4-carboxamide (TR) at micromolar concentrations reduces salvage of exogenous pyrimidine and purine nucleosides by cultured L1210 cells. Uridine transport into erythrocytes is inhibited 62-69% by 0.5 mM concentration of the drug. Neither the parent drug nor its monophosphate or triphosphate derivatives inhibited uridine/cytidine kinase in vitro. When L1210 cells were washed free of drug prior to incubation with [14C]uridine approximately 50% inhibition of uridine uptake remained. Incubation of L1210 cells with the drug resulted in an increase in the uracil nucleotide pool. These results indicate that TR reduces uridine uptake by L1210 cells via a combination of inhibition at the transport site and inhibition of uridine/cytidine kinase due to an increased uracil nucleotide pool.