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Article

Leukemia cells are sensitized to temozolomide, carmustine and melphalan by the inhibition of O6‑methylguanine‑DNA methyltransferase

  • Authors:
    • Hajime Arai
    • Takahiro Yamauchi
    • Kanako Uzui
    • Takanori Ueda
  • View Affiliations / Copyright

    Affiliations: Department of Hematology and Oncology, Faculty of Medical Sciences, University of Fukui, Eiheiji, Fukui 910‑1193, Japan
  • Pages: 845-849
    |
    Published online on: June 2, 2015
       https://doi.org/10.3892/ol.2015.3307
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Abstract

The cytotoxicity of the monofunctional alkylator, temozolomide (TMZ), is known to be mediated by mismatch repair (MMR) triggered by O6‑alkylguanine. By contrast, the cytotoxicity of bifunctional alkylators, including carmustine (BCNU) and melphalan (MEL), depends on interstrand crosslinks formed through O6‑alkylguanine, which is repaired by nucleotide excision repair and recombination. O6‑alkylguanine is removed by O6‑methylguanine‑DNA methyltransferase (MGMT). The aim of the present study was to evaluate the cytotoxicity of TMZ, BCNU and MEL in two different leukemic cell lines (HL‑60 and MOLT‑4) in the context of DNA repair. The transcript levels of MGMT, ERCC1, hMLH1 and hMSH2 were determined using reverse transcription‑quantitative polymerase chain reaction. In addition, the proliferation was measured using the trypan blue exclusion assay. Drug sensitivity was found to vary between the two cell lines. Treatment of the cells with TMZ, BCNU or MEL in combination with O6‑benzylguanine, an MGMT inhibitor, was demonstrated to sensitize the two cell lines to these agents. However, the extent of sensitization was not found to be correlated with the expression levels of MGMT transcripts. Furthermore, the drug sensitivity was also not associated with the transcript levels of ERCC1, hMLH1 and hMSH2. Thus, leukemic cells were sensitized to alkylating agents by the inhibition of MGMT.
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Copy and paste a formatted citation
Spandidos Publications style
Arai H, Yamauchi T, Uzui K and Ueda T: Leukemia cells are sensitized to temozolomide, carmustine and melphalan by the inhibition of O6‑methylguanine‑DNA methyltransferase. Oncol Lett 10: 845-849, 2015.
APA
Arai, H., Yamauchi, T., Uzui, K., & Ueda, T. (2015). Leukemia cells are sensitized to temozolomide, carmustine and melphalan by the inhibition of O6‑methylguanine‑DNA methyltransferase. Oncology Letters, 10, 845-849. https://doi.org/10.3892/ol.2015.3307
MLA
Arai, H., Yamauchi, T., Uzui, K., Ueda, T."Leukemia cells are sensitized to temozolomide, carmustine and melphalan by the inhibition of O6‑methylguanine‑DNA methyltransferase". Oncology Letters 10.2 (2015): 845-849.
Chicago
Arai, H., Yamauchi, T., Uzui, K., Ueda, T."Leukemia cells are sensitized to temozolomide, carmustine and melphalan by the inhibition of O6‑methylguanine‑DNA methyltransferase". Oncology Letters 10, no. 2 (2015): 845-849. https://doi.org/10.3892/ol.2015.3307
Copy and paste a formatted citation
x
Spandidos Publications style
Arai H, Yamauchi T, Uzui K and Ueda T: Leukemia cells are sensitized to temozolomide, carmustine and melphalan by the inhibition of O6‑methylguanine‑DNA methyltransferase. Oncol Lett 10: 845-849, 2015.
APA
Arai, H., Yamauchi, T., Uzui, K., & Ueda, T. (2015). Leukemia cells are sensitized to temozolomide, carmustine and melphalan by the inhibition of O6‑methylguanine‑DNA methyltransferase. Oncology Letters, 10, 845-849. https://doi.org/10.3892/ol.2015.3307
MLA
Arai, H., Yamauchi, T., Uzui, K., Ueda, T."Leukemia cells are sensitized to temozolomide, carmustine and melphalan by the inhibition of O6‑methylguanine‑DNA methyltransferase". Oncology Letters 10.2 (2015): 845-849.
Chicago
Arai, H., Yamauchi, T., Uzui, K., Ueda, T."Leukemia cells are sensitized to temozolomide, carmustine and melphalan by the inhibition of O6‑methylguanine‑DNA methyltransferase". Oncology Letters 10, no. 2 (2015): 845-849. https://doi.org/10.3892/ol.2015.3307
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