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Modeling Colitis-Associated Cancer with Azoxymethane AOM and Dextran Sulfate Sodium DSS
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The Azoxymethane/Il10 -/- Model of Colitis-Associated Cancer (CAC)

Aaron Rothemich1, Janelle C Arthur2,3,4

  • 1Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Methods in Molecular Biology (Clifton, N.J.)
|February 25, 2019
PubMed

Insights

The azoxymethane/interleukin-10 knockout mouse model effectively mimics human colorectal cancer by integrating inflammation and gut microbiota. This study details using Escherichia coli NC101 and AOM to investigate these factors in colon tumorigenesis.

Area of Science:

  • Gastroenterology
  • Oncology
  • Microbiology

Background:

  • Mouse models are crucial for understanding human disease mechanisms.
  • The azoxymethane/interleukin-10 knockout (AOM/Il10-/-) model simulates colitis-associated colorectal cancer (CAC).
  • This model is relevant to inflammatory bowel disease (IBD)-associated colon cancer, reflecting inflammation's role in human colorectal cancer.

Purpose of the Study:

  • To detail the methodology of the AOM/Il10-/- mouse model for studying colon tumorigenesis.
  • To investigate the impact of intestinal microbiota and inflammation on colorectal cancer development.
  • To describe the process of bacterial colonization, carcinogen administration, and subsequent analysis.

Main Methods:

  • Utilizing inflammation-susceptible Il10-/- mice.
  • Administering the colon-specific carcinogen azoxymethane (AOM) intraperitoneally.
  • Colonizing mice with the pathobiont Escherichia coli strain NC101.
  • Quantifying bacterial load and performing histologic assessment of inflammation and cancer.

Main Results:

  • The AOM/Il10-/- model allows for the assessment of microbiota and inflammation's effects on colon tumorigenesis.
  • AOM induces mutagenesis and colorectal tumorigenesis in an inflammation-dependent manner in Il10-/- mice.
  • The presence and composition of the intestinal microbiota drive inflammation-induced tumorigenesis in this model.

Conclusions:

  • The AOM/Il10-/- model, combined with specific bacterial challenges like E. coli NC101, provides a robust platform for studying colorectal cancer.
  • This model recapitulates key molecular aspects of inflammation's role in human colorectal cancer.
  • Further research using this model can elucidate mechanisms linking gut microbiota, inflammation, and colon cancer progression.
Keywords:
Colitis-associated colorectal cancerEscherichia coliGnotobioticIl10−/− mouseInflammatory bowel diseasesIntestinal inflammation

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