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Selective decrease in the DNA base excision repair pathway in squamous cell cancer of the esophagus.

Pramod Bonde1, Daqing Gao, Lei Chen

  • 1Cardiothoracic-Renal Research Program, Johns Hopkins University School of Medicine, Baltimore, Md 21205, USA.

The Journal of Thoracic and Cardiovascular Surgery
|January 3, 2007
PubMed
Summary
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Oxidative DNA damage is elevated in esophageal tumors. The DNA repair enzyme 8-oxoguanine glycosylase is upregulated in adenocarcinoma but decreased in squamous cell carcinoma, indicating pathway alterations.

Area of Science:

  • Oncology
  • Molecular Biology
  • DNA Repair

Background:

  • Oxidative damage generates 8-oxoguanine, a mutagenic lesion mispairing with adenine.
  • 8-Oxoguanine glycosylase initiates DNA base excision repair (BER) in mammalian cells.
  • No prior studies investigated oxidative DNA damage or repair in esophageal cancer.

Purpose of the Study:

  • To investigate DNA damage and repair pathways in esophageal cancer.
  • To assess 8-oxoguanine glycosylase expression in reflux- and mutagen-induced esophageal tumors.
  • To correlate DNA damage and repair with apoptosis in esophageal cancer models.

Main Methods:

  • Rats underwent surgical induction of gastroduodenal reflux, with half receiving methyl-n-amyl nitrosamine.
  • Control rats (n=10) received no surgical or chemical treatment.

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  • Immunohistochemistry and Western blot analyzed 8-oxoguanine and 8-oxoguanine glycosylase expression at 30 weeks.

    • Main Results:

    • Significantly increased 8-oxoguanine expression (DNA damage) in both adenocarcinoma and squamous cell carcinoma compared to controls.
    • 8-Oxoguanine glycosylase was upregulated in adenocarcinoma but significantly decreased in squamous cell carcinoma.
    • Active apoptosis pathways correlated with 8-oxoguanine expression in both cancer types.

    Conclusions:

    • Demonstrates elevated oxidative DNA damage in esophageal tumors.
    • Highlights a selective decrease in the DNA base excision repair pathway in squamous cell carcinoma.
    • Suggests distinct DNA repair alterations in different esophageal cancer subtypes.