Effect of tetrahydrouridine on metabolism and transport of 1-beta-D-arabinofuranosylcytosine in human cells

Chemotherapy. 1992;38(5):358-66. doi: 10.1159/000239026.


Deamination of cytosine arabinoside (ara-C) by cytidine deaminase is the main mode of inactivation of this drug which can be responsible for ara-C resistance. The present study was undertaken to determine the effect of tetrahydrouridine (THU; a potent inhibitor of cytidine deaminase) on ara-C transport and metabolism in human cells. A rapid transport of ara-C into freshly isolated hepatocytes and an increased intracellular accumulation of the unchanged drug were observed in the presence of 50 micrograms/ml THU. THU inhibited the intracellular deamination of ara-C by 80% and slowed elimination of the compound extracellularly. The intracellular ara-C concentrations achieved after incubation with 1 micrograms/ml ara-C plus 50 micrograms/ml THU are similar to those attained with ara-C (10 micrograms/ml) alone. Treatment of leukemic K562 cells with the combination of THU (50 micrograms/ml) and ara-C (1 micrograms/ml) led to an augmentation of intracellular ara-C triphosphate formation up to twofold.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Cytarabine / blood
  • Cytarabine / metabolism
  • Cytarabine / pharmacokinetics*
  • Humans
  • Leukemia, Experimental / metabolism
  • Liver / cytology
  • Liver / enzymology
  • Liver / metabolism*
  • Nucleoside Deaminases / metabolism
  • Tetrahydrouridine / pharmacology*
  • Tumor Cells, Cultured


  • Cytarabine
  • Tetrahydrouridine
  • Nucleoside Deaminases