The Azoxymethane/Il10 -/- Model of Colitis-Associated Cancer (CAC)

Methods Mol Biol. 2019:1960:215-225. doi: 10.1007/978-1-4939-9167-9_19.

Abstract

Mouse models have proved essential for generating a mechanistic understanding of human disease processes. The azoxymethane/interleukin-10 knockout (AOM/Il10-/-) model is a powerful tool for assessing the effects of intestinal microbiota and inflammation on colon tumorigenesis. This model of colitis-associated colorectal cancer (CAC) is particularly relevant to inflammatory bowel disease (IBD)-associated colon cancer and recapitulates many of the molecular effects underlying inflammation's influence on human colorectal cancer. The model utilizes inflammation-susceptible Il10-/- mice injected intraperitoneally (i.p.) with the colon-specific carcinogen AOM. AOM and its metabolites cause mutagenesis and colorectal tumorigenesis in an inflammation-dependent manner, which in Il10-/- mice is driven by the presence and composition of the intestinal microbiota. Here we describe bacterial colonization with the pathobiont Escherichia coli strain NC101, cancer initiation with AOM, bacterial quantification, and histologic assessment of inflammation and cancer.

Keywords: Colitis-associated colorectal cancer; Escherichia coli; Gnotobiotic; Il10−/− mouse; Inflammatory bowel diseases; Intestinal inflammation.

MeSH terms

  • Animals
  • Azoxymethane / toxicity*
  • Colitis / complications*
  • Colitis / metabolism
  • Colorectal Neoplasms / chemically induced
  • Colorectal Neoplasms / etiology*
  • Colorectal Neoplasms / metabolism
  • Disease Models, Animal
  • Germ-Free Life
  • Inflammation / immunology
  • Inflammation / metabolism
  • Inflammatory Bowel Diseases / complications
  • Inflammatory Bowel Diseases / metabolism
  • Interleukin-10 / deficiency*
  • Intestines / immunology
  • Mice, Knockout

Substances

  • Interleukin-10
  • Azoxymethane