The mechanism of 3'-azido-2',3'-dideoxythymidine resistance to human lymphoid cells

  • Authors:
    • Gerold Hoever
    • Bettina Groeschel
    • Prakash Chandra
    • Hans W. Doerr
    • Jindrich Cinatl
  • View Affiliations

  • Published online on: June 1, 2003     https://doi.org/10.3892/ijmm.11.6.743
  • Pages: 743-747
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Abstract

The human T-lymphoid cell line H9 resistant to 3'-azido-2',3'-dideoxythymidine (AZT) has a very low level of thymidine kinase (TK) expression which accounts for the failure of AZT to inhibit HIV-1 replication. In the present study DNA methylation and histone deacetylation as possible mechanisms of decreased TK gene expression in the resistant cells were investigated. The resistant cells expressed high levels of DNA methyltransferases (DNMTs) 3a and 3b. The DNA methylation inhibitor, 5-aza-cytidine (5-aza-C), increased TK gene expression and antiviral activity of AZT in the resistant cells, while histone deacetylase inhibitor trichostatin A (TSA) had no effect. The results suggest that hypermethylation of the TK gene but not histone deacetylation in AZT-resistant H9 cells accounts for decreased TK gene expression and failure of AZT to inhibit HIV-1 replication probably due to overexpression of DNMT 3a and 3b.

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June 2003
Volume 11 Issue 6

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Hoever G, Groeschel B, Chandra P, Doerr HW and Cinatl J: The mechanism of 3'-azido-2',3'-dideoxythymidine resistance to human lymphoid cells. Int J Mol Med 11: 743-747, 2003.
APA
Hoever, G., Groeschel, B., Chandra, P., Doerr, H.W., & Cinatl, J. (2003). The mechanism of 3'-azido-2',3'-dideoxythymidine resistance to human lymphoid cells. International Journal of Molecular Medicine, 11, 743-747. https://doi.org/10.3892/ijmm.11.6.743
MLA
Hoever, G., Groeschel, B., Chandra, P., Doerr, H. W., Cinatl, J."The mechanism of 3'-azido-2',3'-dideoxythymidine resistance to human lymphoid cells". International Journal of Molecular Medicine 11.6 (2003): 743-747.
Chicago
Hoever, G., Groeschel, B., Chandra, P., Doerr, H. W., Cinatl, J."The mechanism of 3'-azido-2',3'-dideoxythymidine resistance to human lymphoid cells". International Journal of Molecular Medicine 11, no. 6 (2003): 743-747. https://doi.org/10.3892/ijmm.11.6.743