title: Head and neck cancer cell lines exhibit differential mitochondrial repair deficiency in response to 4NQO.
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.
authors.affiliation: The John Hopkins University School of Medicine, Head and Neck Cancer Research Division, Department of Otolaryngology--Head and Neck Surgery, 601 N. Caroline Street, 6th Floor, Baltimore, MD 21287-0910, USA.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Kim
authors.forename: Chad A
authors.initials: CA
authors.lastname: Glazer
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Mambo
authors.forename: Aditi
authors.initials: A
authors.lastname: Chatterjee
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
authors.forename: David
authors.initials: D
authors.lastname: Sidransky
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Califano
mesh_terms: D015112:4-Nitroquinoline-1-oxide / Q000633:toxicity; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D018736:DNA Adducts / Q000096:biosynthesis / Q000187:drug effects; D004249:DNA Damage; D004260:DNA Repair; D004272:DNA, Mitochondrial / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D004273:DNA, Neoplasm / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology; D006801:Humans; D018384:Oxidative Stress; D016133:Polymerase Chain Reaction / Q000379:methods; D015363:Quinolones / Q000633:toxicity*; D014407:Tumor Cells, Cultured
chemical_list: C120195:4-nitroquinolone-1-oxide; D018736:DNA Adducts; D004272:DNA, Mitochondrial; D004273:DNA, Neoplasm; D015363:Quinolones; D015112:4-Nitroquinoline-1-oxide