Mariangela De Robertis1, Emanuela Massi1, Maria Luana Poeta2, Simone Carotti3, Sergio Morini3, Loredana Cecchetelli4, Emanuela Signori5, Vito Michele Fazio6
1Laboratory of Molecular Medicine and Biotechnology, CIR, Campus Bio-Medico University of Rome, Via Álvaro del Portillo 21 – 00128 Rome, Italy
2Department of General and Environmental Physiology and Center of Excellence in Comparative Genomics (CEGBA), University of Bari, 70126, Bari, Italy
3Department of Biomedical Research (CIR), University Campus Bio-Medico of Rome, Via Álvaro del Portillo 21 – 00128 Rome, Italy
4IBI Istituto Biochimico Italiano Giovanni Lorenzini, Via Fossignano, 2 – 04011 Aprilia (LT), Italy
5Institute of Translational Pharmacology. Laboratory of Molecular Pathology and Experimental Oncology. National Research Council (CNR), Via Fosso del Cavaliere 100, 00133 Rome, Italy
6Laboratory of Molecular Medicine and Biotechnology, CIR, Campus Bio-Medico University of Rome, Via Álvaro del Portillo 21 – 00128 Rome; Laboratory of Oncology, IRCCS ‘Casa Sollievo della Sofferenza,’ Viale Padre Pio, 71013 San Giovanni Rotondo (FG), Italy
DOI: 10.4103/1477-3163.78279
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-pronemicroenvironment. 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. Keywords: Animal model, chemical carcinogens, colorectal carcinogenesis, preclinical studies