Arabinosylcytosine downregulates thymidine kinase and induces cross-resistance to zidovudine in T-lymphoid cells

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

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

The aim of this study was to determine molecular mechanism(s) responsible for the reduced thymidine kinase activity (TK) observed earlier in an arabinosylcytosine (araC) resistant lymphoid cell line (H9-araC cells), which was obtained following continuous cultivation of H9 cells in the presence of 0.5μM araC. Compared to H9 cells, in H9-araC cells TK1 and TK2 gene expressions were reduced to 17.7% and 2.5%, respectively, and the cellular AZT accumulation was diminished to 35.8%. These cells were also found cross-resistant to azidothymidine (42-fold). There was no significant difference in the expression of MDR1, MRP4 or TK protein. The lack of correlation between the expressions of TK protein and TK1 and TK2 suggests that post-translational factors may also play a role in the reduced TK activity in H9-araC cells. These findings suggest that araC affects TK expression at the genetic level.

Original languageEnglish (US)
Pages (from-to)564-568
Number of pages5
JournalBiochemical and biophysical research communications
Volume307
Issue number3
DOIs
StatePublished - Aug 1 2003

Keywords

  • Arabinosylcytosine
  • Azidothymidine resistance
  • Cross-resistance
  • Deoxycytidine kinase
  • Thymidine kinase 1
  • Thymidine kinase 2

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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