Assessment of the significance of mitochondrial DNA damage by chemotherapeutic agents

  • Authors:
    • Soo Lo
    • Berend Tolner
    • Jan-Willem Taanman
    • J. Mark Cooper
    • Mei Gu
    • John A. Hartley
    • Anthony H.V. Schapira
    • Daniel Hochhauser
  • View Affiliations

  • Published online on: August 1, 2005     https://doi.org/10.3892/ijo.27.2.337
  • Pages: 337-344
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Abstract

The pathways which are activated following damage to nuclear DNA in cancer cells are well understood. There is evidence that treatment with several chemotherapeutic agents may result in damage to mitochondrial DNA. This study investigated the contribution of mitochondrial DNA to cytotoxicity of DNA-interactive agents. To understand the significance of drug interactions with mitochondrial DNA, we investigated A549 non-small cell lung cancer cell lines and their ρ0 derivatives in which mitochondrial DNA has been eradicated. The parental cell line showed increased sensitivity to the anthracycline daunorubicin when compared with the A549 ρ0 line. In addition, the A549 ρ0 line was resistant to the rhodacyanine derivative, MKT-077, which has been shown to interact with mitochondrial DNA. Southern blotting demonstrated that MKT-077 mediated damage to mitochondrial but not nuclear DNA. Restoration of mitochondrial DNA by formation of cybrids restored sensitivity to these agents. The mitochondrial DNA damage, following treatment of A549 ρ0 cells with MKT-077, resulted in G2 arrest which was not mediated by expression of p53. Mitochondrial DNA is a critical target for MKT-077 and daunorubicin, and is a potential target for novel chemotherapeutic agents.

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August 2005
Volume 27 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Lo S, Tolner B, Taanman J, Cooper JM, Gu M, Hartley JA, Schapira AH and Hochhauser D: Assessment of the significance of mitochondrial DNA damage by chemotherapeutic agents. Int J Oncol 27: 337-344, 2005
APA
Lo, S., Tolner, B., Taanman, J., Cooper, J.M., Gu, M., Hartley, J.A. ... Hochhauser, D. (2005). Assessment of the significance of mitochondrial DNA damage by chemotherapeutic agents. International Journal of Oncology, 27, 337-344. https://doi.org/10.3892/ijo.27.2.337
MLA
Lo, S., Tolner, B., Taanman, J., Cooper, J. M., Gu, M., Hartley, J. A., Schapira, A. H., Hochhauser, D."Assessment of the significance of mitochondrial DNA damage by chemotherapeutic agents". International Journal of Oncology 27.2 (2005): 337-344.
Chicago
Lo, S., Tolner, B., Taanman, J., Cooper, J. M., Gu, M., Hartley, J. A., Schapira, A. H., Hochhauser, D."Assessment of the significance of mitochondrial DNA damage by chemotherapeutic agents". International Journal of Oncology 27, no. 2 (2005): 337-344. https://doi.org/10.3892/ijo.27.2.337