2′, 3′-Dideoxycytidine represses thymidine kinases 1 and 2 expression in T-lymphoid cells

Tieran Han, Marilyn Fernandez, Malancha Sarkar, Ram P. Agarwal

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

In vitro culture of H9 human lymphoid cells in the presence of 5.0 μM dideoxycytidine (ddC), for about 40-45 days, selected cells (H9-ddC cells), which were resistant to the drug and cross-resistant to AZT (zidovudine) and 5-fluoro-2′-deoxyuridine (FdUR). The major mechanism of cross-resistance to AZT and FdUR in these cells was low cellular activity of thymidine kinase (TK). To explore molecular mechanisms of the reduced TK activity in H9-ddC cells, the mRNA expression of TK1 and TK2 and western blot analysis of TK1 protein were performed. RT-PCR analysis revealed that in H9-ddC cells the expression of both TK1 and TK2 mRNA was reduced to 27.1% and 79.4%, respectively. The reduced TK1 gene expression was confirmed by an absence of a detectable TK1 protein band in western blot of H9-ddC cells. These results demonstrate that long-term treatment of H9 cells in the presence of ddC down-regulated TK1 and TK2 gene expression and reduced the expression and activity of TK in the resistant cells.

Original languageEnglish (US)
Pages (from-to)835-842
Number of pages8
JournalLife Sciences
Volume74
Issue number7
DOIs
StatePublished - Jan 2 2004

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Keywords

  • Cross-resistance
  • Deoxycytidine kinase
  • Dideoxycytidine
  • Gene down regulation
  • Thymidine kinase 2
  • Thymidine kinase1

ASJC Scopus subject areas

  • Pharmacology

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