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Inhibitory Effect of 2′,2′-Difluorodeoxycytidine on Cytidine 5′-Triphosphate Synthetase

  • V. Heinemann
  • W. Plunkett
Conference paper
Part of the Haematology and Blood Transfusion / Hämatologie und Bluttransfusion book series (HAEMATOLOGY, volume 36)

Abstract

2′,2′-Difluorodeoxycytidine (dFdC) is a deoxycytidine analog which induces inhibition of DNA synthesis and cell death [1]. dFdC is intracellularly phosphorylated by deoxycytidine kinase and the 5′-triphosphate (dFdCTP) accumulates as the main metabolite. Elimination of intracellular dFdCTP is biphasic, an observation also reported for circulating leukemia cells [2]. dFdC was shown to act as an inhibitor of several cellular enzyme systems: ribonucleotide reductase [3], deoxycytidylate deaminase [4], and DNA polymerases [5]. Investigations in a number of cell lines demonstrated a depletion of cellular CTP pools after exposure of cells to dFdC. The present study investigates this CTP depletion in CHO cells and provides evidence for the hypothesis that high concentrations of dFdCTP are inhibitory to CTP synthetase. It is further hypothesized that a relation may exist between dFdC-mediated depletion of cellular CTP pools and inhibition of RNA synthesis.

Keywords

Ribonucleotide Reductase Ehrlich Ascites Tumor Cell Deoxycytidine Kinase High Cellular Concen Deoxycytidylate Deaminase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag Berlin Heidelberg 1994

Authors and Affiliations

  • V. Heinemann
    • 1
  • W. Plunkett
    • 2
  1. 1.III Medizinische Klinik, Klinikum GrosshadernUniversity of MunichGermany
  2. 2.Department of Medical Oncology, M.D. Anderson Cancer CenterThe University of TexasHoustonUSA

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