Murine Models of Sporadic and Inflammation-Related Colon Carcinogenesis with Particular Focus on the AOM/DSS Chemically Induced Colorectal Cancer Model.

Colorectal cancer (CRC) is the third most common malignancy in the world. It is a life-threatening disease that can develop spontaneously or as a long-term complication of an inflammatory status. Inflammation can indeed provide initiating and promoting stimuli and mediators, generating a tumour-prone microenvironment. Although inflammation-linked carcinogenesis is a well accepted concept and is often observed within the gastrointestinal tract, the underlying mechanisms remain to be elucidated. Furthermore, the risk for CRC is also influenced by a genetic predisposition, which is especially high for somatic mutations of the tumor suppressor gene adenomatosis polyposis coli (APC), causing familial adenomatosis coli. Animal models are essential tools for the understanding of human CRC and for the preclinical testing of novel therapeutic options in vivo. 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. Although none of these models reflects all aspects of CRC, they complement each other to provide suitable tools for specific tasks. In this chapter, we discuss the principal features of different CRC models, con-sidering they own benefits and limits. Then we will focus our attention on the chemically-induced CRC murine models reported in the literature as highly valuable and powerful model systems. Among them, the azoxymethane/dextran sodium sulphate (AOM/DSS) murine model is considered as a reliable practical tool, since the tumor development is predictable and consistent, with a high incidence of affected animals in a narrow time frame. More importantly, this model reproduces many aspects of human CRC development and it offers the possibility to study the earliest succession of events underlying tumor initiation, when single aberrant crypts appear in colonic mucosa. For this reason, the AOM/DSS model has become an outstanding model for studying the early molecular events, still partially unknown in humans, that act in the preneoplastic phase of colon carcinogenesis and which are fundamental in CRC development, representing a powerful platform also useful in chemo preventive intervention studies.