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

@article{Innoceta2004MolecularBO,
  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},
  year={2004},
  volume={231},
  pages={173-177}
}
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
TLDR
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.

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