Mitochondrial DNA is a sensitive surrogate and oxidative stress target in oral cancer cells.

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  • Author(s): Tan J;Tan J; Dong X; Dong X; Liu H; Liu H; Liu H
  • Source:
    PloS one [PLoS One] 2024 Sep 03; Vol. 19 (9), pp. e0304939. Date of Electronic Publication: 2024 Sep 03 (Print Publication: 2024).
  • Publication Type:
    Journal Article
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
    • Publication Information:
      Original Publication: San Francisco, CA : Public Library of Science
    • Subject Terms:
      DNA, Mitochondrial*/genetics ; DNA, Mitochondrial*/metabolism ; Oxidative Stress*/drug effects ; Mouth Neoplasms*/genetics ; Mouth Neoplasms*/pathology ; Mouth Neoplasms*/metabolism ; DNA Damage* ; Hydrogen Peroxide*/pharmacology ; Reactive Oxygen Species*/metabolism; Humans ; Cell Line, Tumor ; DNA Repair ; Apoptosis/drug effects ; DNA Copy Number Variations
    • Abstract:
      Cellular oxidative stress mediated by intrinsic and/or extrinsic reactive oxygen species (ROS) is associated with disease pathogenesis. Oxidative DNA damage can naturally be substituted by mitochondrial DNA (mtDNA), leading to base lesion/strand break formation, copy number changes, and mutations. In this study, we devised a single test for the sensitive quantification of acute mtDNA damage, repair, and copy number changes using supercoiling-sensitive quantitative PCR (ss-qPCR) and examined how oxidative stress-related mtDNA damage responses occur in oral cancer cells. We observed that exogenous hydrogen peroxide (H2O2) induced dynamic mtDNA damage responses, as reflected by early structural DNA damage, followed by DNA repair if damage did not exceed a particular threshold. However, high oxidative stress levels induced persistent mtDNA damage and caused a 5-30-fold depletion in mtDNA copy numbers over late responses. This dramatic depletion was associated with significant growth arrest and apoptosis, suggesting persistent functional consequences. Moreover, oral cancer cells responded differentially to oxidative injury when compared with normal cells, and different ROS species triggered different biological consequences under stress conditions. In conclusion, we developed a new method for the sensitive detection of mtDNA damage and copy number changes, with exogenous H2O2 inducing dynamic mtDNA damage responses associated with functional changes in stressed cancer cells. Finally, our method can help characterize oxidative DNA damage in cancer and other human diseases.
      Competing Interests: The authors have declared that no competing interests exist.
      (Copyright: © 2024 Tan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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    • Accession Number:
      0 (DNA, Mitochondrial)
      BBX060AN9V (Hydrogen Peroxide)
      0 (Reactive Oxygen Species)
    • Publication Date:
      Date Created: 20240903 Date Completed: 20240903 Latest Revision: 20240906
    • Publication Date:
      20240906
    • Accession Number:
      PMC11371132
    • Accession Number:
      10.1371/journal.pone.0304939
    • Accession Number:
      39226291