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


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2002-02

AUTHORS

Annamaria Innoceta, Luca Galluzzi, Annamaria Ruzzo, Francesca Andreoni, Laura Chiarantini, Mauro Magnani

ABSTRACT

Human monoblastoid cells (U937) grown in the presence of therapeutically relevant dideoxycytidine concentrations (0.1 microM) become resistant to the drug thanks to an altered deoxycytidine kinase. In this paper we show that deoxycytidine kinase mRNA is significantly reduced in drug-resistant U937 cells (U937-R) although the deoxycytidine kinase promoter is normal. Anumber of nucleotide deletions, insertions and substitutions was found in the coding region of deoxycytidine kinase gene. Several identified mutations result in truncated forms of the enzyme or in the introduction of stop codons: in one case a complete lack of exon 4 was found. Thus, the deoxycytidine kinase gene accumulates mutations at a very high rate, as already reported for other cytidine analogues (i.e. Ara C) suggesting that the design of new antiviral or anticancer drugs of the cytidine family should take into account the potential development of cell resistance as a critical factor in drug failure. More... »

PAGES

173-177

References to SciGraph publications

  • 1997-06. Zalcitabine in DRUGS
  • 1994-04. New targets for pyrimidine antimetabolites for the treatment of solid tumours in INTERNATIONAL JOURNAL OF CLINICAL PHARMACY
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1023/a:1014441209108

    DOI

    http://dx.doi.org/10.1023/a:1014441209108

    DIMENSIONS

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    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/11952160


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