The AOM/DSS murine model for the study of colon carcinogenesis: From pathways to diagnosis and therapy studies

Mariangela Robertis, Emanuela Massi, Maria Poeta, Simone Carotti, Sergio Morini, Loredana Cecchetelli, Emanuela Signori, Vito Fazio

Research output: Contribution to journalArticlepeer-review

Abstract

Colorectal cancer (CRC) is a major health problem in industrialized countries. Although inflammation-linked carcinogenesis is a well accepted concept and is often observed within the gastrointestinal tract, the underlying mechanisms remain to be elucidated. Inflammation can indeed provide initiating and promoting stimuli and mediators, generating a tumour-prone microenvironment. Many murine models of sporadic and inflammation-related colon carcinogenesis have been developed in the last decade, including chemically induced CRC models, genetically engineered mouse models, and xenoplants. Among the chemically induced CRC models, the combination of a single hit of azoxymethane (AOM) with 1 week exposure to the inflammatory agent dextran sodium sulphate (DSS) in rodents has proven to dramatically shorten the latency time for induction of CRC and to rapidly recapitulate the aberrant crypt foci-adenoma-carcinoma sequence that occurs in human CRC. Because of its high reproducibility and potency, as well as the simple and affordable mode of application, the AOM/DSS has become an outstanding model for studying colon carcinogenesis and a powerful platform for chemopreventive intervention studies. In this article we highlight the histopathological and molecular features and describe the principal genetic and epigenetic alterations and inflammatory pathways involved in carcinogenesis in AOM/DSS-treated mice; we also present a general overview of recent experimental applications and preclinical testing of novel therapeutics in the AOM/DSS model.

Original languageEnglish
Article number9
JournalJournal of Carcinogenesis
Volume10
DOIs
Publication statusPublished - 2011

Keywords

  • Animal model
  • chemical carcinogens
  • colorectal carcinogenesis
  • preclinical studies

ASJC Scopus subject areas

  • Cancer Research
  • Health, Toxicology and Mutagenesis
  • Oncology

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