Abstract
Liver is the main organ in the elimination of 5-fluorouracil (5FU). Rat hepatocytes and hepatoma cells (H35) were incubated in monolayer in the presence of 0, 17, 50 and 100 μM 5FU for 4 hrs. The metabolism of 5FU was monitored with [3H]5FU, the protein synthesis was determined by the incorporation of [14C]leucine and glycoconjugate synthesis by incorporation of [3H]GlcNH2 and [3H]fucose. In rat hepatocytes the amount of soluble fluoronu-cleotides was dependent on the concentration of 5FU. With 50 μM 5FU the concentrations of FUDP-HexNAc, FUDP-hexose and FUTP were 17, 5 and 9 pmol/106 hepatocytes. In the presence of 0.5 mM thymine to inhibit the catabolism of 5FU, these concentrations were 23, 29 and 49 pmol/106 hepatocytes, resp. The effect of thymine at 17 and 100 μM 5FU was comparable. The incorporation of 5FU into RNA was also concentration dependent and was 72 pmol/106 hepatocytes at 50 μM 5FU. In contrast to nucleotide synthesis thymine enhanced the incorporation of 5FU into RNA only less than 1.5 fold at all 5FU concentrations. In H35 cells both synthesis of soluble fluoronucleotides and the incorporation of 5FU into RNA was linear with the concentration of 5FU. At 50 μM 5FU the amounts of FUDP-HexNAC, FUDP-hexose and FUTP were 30, 68 and 106 pmol/106 cells, and 345 pmol 5FU/106 cells was incorporated into RNA. In both cell types incubation with 5FU had no effect on the incorporation of leucine into proteins and of sugars into glycoconjugates.
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Pels Rijcken, W., Telleman, F., Peters, G. et al. 125 INCORPORATION OF 5-FLUOROURACIL INTO NUCLEOTIDE SUGARS AND THE EFFECT ON GLYCOCONJUGATES IN RAT HEPATOMA CELLS AND HEPATOCYTES. Pediatr Res 24, 132 (1988). https://doi.org/10.1203/00006450-198807000-00149
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DOI: https://doi.org/10.1203/00006450-198807000-00149