Head and neck cancer cell lines exhibit differential mitochondrial repair deficiency in response to 4NQO

Michael M. Kim, Chad A. Glazer, Elizabeth Mambo, Aditi Chatterjee, Ming Zhao, David Sidransky, Joseph A. Califano

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Constituents of tobacco can cause DNA adduct formation and are implicated in head and neck squamous cell cancer (HNSC) development. We investigated the capacity of HNSC cell lines to repair mitochondrial DNA (mtDNA) damage induced by a DNA adduct-forming agent. HNSC cell lines underwent 4-nitroquinoline 1-oxide (4NQO) exposure with subsequent rescue with normal media. Real-time quantitative PCR for nuclear DNA (nDNA) and mtDNA was performed. mtDNA to nDNA ratios were calculated and standardized to mock-treated cells to assess mtDNA repair ability. Two of three tested cancer cell lines exposed to 4NQO exhibited consistent decreases in mtDNA/nDNA ratios throughout the different repair timepoints. At 24 h mtDNA/nDNA ratios of JHU-O19 and JHU-O22 decreased to 63% and 60% of controls, respectively. Conversely, a control keratinocyte cell line exhibited overall increases in mtDNA/nDNA ratios compared to baseline suggesting intact DNA repair mechanisms. By using a DNA adduct formation and repair model featuring 4NQO and HNSC cell lines, we have implicated faulty mtDNA repair as having a potential role in HNSC.

Original languageEnglish (US)
Pages (from-to)201-207
Number of pages7
JournalOral Oncology
Volume42
Issue number2
DOIs
StatePublished - Feb 1 2006

Keywords

  • DNA adduct formation
  • DNA damage repair
  • Mitochondrial DNA
  • Oxidative injury
  • Quantitative PCR

ASJC Scopus subject areas

  • Oral Surgery
  • Oncology
  • Cancer Research

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