Molecular basis of 2′,3′-dideoxycytidine-induced drug resistance in human cells

  title={Molecular basis of 2′,3′-dideoxycytidine-induced drug resistance in human cells},
  author={Anna Maria Innoceta and Luca Galluzzi and Annamaria Ruzzo and Francesca Andreoni and Laura Chiarantini and Mauro Magnani},
  journal={Molecular and Cellular Biochemistry},
Human monoblastoid cells (U937) grown in the presence of therapeutically relevant dideoxycytidine concentrations (0.1 μM) become resistant to the drug thanks to an altered deoxycytidine kinase. In this paper we show that deoxycytidine kinase mRNA is significally reduced in drug-resistant U937 cells (U937-R) although the deoxycytidine kinase promoter is normal. A number of nucleotide deletions, insertions and substitutions was found in the coding region of deoxycytidine kinase gene. Several… 
Nucleoside analog toxicity and nucleoside kinase deficiency : Effects on mitochondrial DNA
To elucidate the role of TK2 mediated phosphorylation in the cytotoxic effects of nucleoside analogs, a human fibroblast cell line with partial Tk2 deficiency was studied and it was concluded that TK 2 has a major role in supplying deoxyribonucleotides for mtDNA replication and that other pathways of deoxy ribonucleotide synthesis cannot compensate for the loss of this enzyme.


2',3'-Dideoxycytidine induced drug resistance in human cells.
2',3'-Dideoxycytidine metabolism in a new drug-resistant cell line.
Resistance to ddC toxicity may be due to cells' decreased ability to accumulate intracellular ddC anabolites, which may depend on cytoplasmic deoxycytidine kinase.
Characterization of the deoxycytidine kinase promoter in human lymphoblast cell lines.
The promoter of the dCK gene is regulated by a number of ubiquitously expressed transcription factors and may play an important role in the T cell depletion associated with adenosine deaminase and purine nucleoside phosphorylase deficiencies.
High incidence of alternatively spliced forms of deoxycytidine kinase in patients with resistant acute myeloid leukemia.
Findings suggest that the presence of inactive, alternatively spliced dCK mRNA transcripts in resistant AML blasts may contribute to the process of AraC resistance in patients with AML.
The Inhibitory Effect of ddC on Human Immunodeficiency Virus Replication Diminishes in Cells that are Chronically Exposed to the Drug
It is shown that the drug-resistant cells were indistinguishable from normal cells in terms of surface CD4 receptors, and allow ddC-sensitive HIV-1 to replicate in the presence of inhibitory ddC concentrations.
New targets for pyrimidine antimetabolites for the treatment of solid tumours
Modulation of deoxycytidine kinase activity has already been shown to be an effective way to improve the effect of cytarabine and will probably be a target for new therapies.
Cell cycle regulation of deoxycytidine kinase
Zalcitabine. An update of its pharmacodynamic and pharmacokinetic properties and clinical efficacy in the management of HIV infection.
Current data suggest that zalcitabine is a useful antiretroviral agent for inclusion as a component of initial double combination therapy with zidovudine or as part of triple combination therapy including zidvudine plus a protease inhibitor in the management of patients with HIV infection.
RMY: High incidence of alternatively spliced forms of deoxycytidine kinase in patients with resistant acute myeloid leukemia
  • Blood 96:
  • 2000