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Updated: Jul 4, 2026

Non-invasive Assessment of the Efficacy of New Therapeutics for Intestinal Pathologies Using Serial Endoscopic Imaging of Live Mice
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DNA damage induced by chronic inflammation contributes to colon carcinogenesis in mice

Lisiane B Meira1, James M Bugni, Stephanie L Green

  • 1Department of Biological Engineering and Center for Environmental Health Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.

The Journal of Clinical Investigation
|June 4, 2008
PubMed

Insights

DNA repair enzyme alkyladenine DNA glycosylase (Aag) prevents colon cancer by fixing DNA damage caused by inflammation. Aag-deficient mice showed increased DNA damage and tumor development, highlighting Aag's protective role.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Inflammation Biology

Background:

  • Chronic inflammation is a known risk factor for cancer development.
  • Reactive oxygen and nitrogen species (RONS) produced during inflammation can cause DNA damage.
  • The role of DNA damage from RONS in inflammation-driven tumorigenesis is not fully understood.

Purpose of the Study:

  • To investigate the impact of DNA damage from RONS on tumor development during chronic inflammation.
  • To determine the role of alkyladenine DNA glycosylase (Aag) in repairing RONS-induced DNA lesions and preventing inflammation-associated cancer.

Main Methods:

  • A mouse model of episodic inflammatory bowel disease induced by dextran sulfate sodium.
  • Assessment of Aag-mediated DNA repair in response to colonic inflammation.
  • Evaluation of colonic epithelial damage and tumorigenesis in Aag-deficient and wild-type mice.
  • A separate study using a Helicobacter pylori infection model in Aag-deficient and wild-type mice to assess gastric lesions.

Main Results:

  • Aag-mediated DNA repair significantly reduced colonic epithelial damage and the severity of dextran sulfate sodium-induced colon tumorigenesis.
  • Aag-deficient mice accumulated higher levels of RONS-induced DNA base lesions during colonic inflammation.
  • Aag-deficient animals exhibited more severe gastric lesions, precursors to gastric cancer, after chronic Helicobacter pylori infection.

Conclusions:

  • The repair of DNA lesions generated by RONS during chronic inflammation, mediated by Aag, is crucial for preventing colon carcinogenesis.
  • Aag plays a protective role against DNA damage and subsequent tumor development in the context of chronic inflammation and infection.

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