The effect of 5-fluorouracil (5-FU) and doxifluridine on cellular uptake and phosphorylation of thiamin was studied in two different cell systems. Uptake of 14C-Thiamine in human NHIK 3025 cells preincubated for 24 h with 0.05 mM 5-FU or 0.1 mM doxifluridine was increased by 22-26% relative to nontreated control cells. In isolated rat hepatocytes a drug-induced increase in thiamin uptake by 40-45% was found following 2 h incubation both with 5-FU and doxifluridine. High performance liquid chromatography (HPLC) showed an increase in intracellular thiamin diphosphate (TPP), while free thiamin (T) remained unchanged in drug-exposed cells, indicating an increased phosphorylation of thiamin. The results indicate that fluoropyrimidines may increase the cellular thiamin metabolism, possibly resulting in clinical symptoms of thiamin deficiency if the dietary intake is not increased correspondingly.
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