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

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.

Absent in melanoma 2 proteins in the development of cancer

“…Among the chemically induced colitis-associated cancer (CAC) mouse models, a single injection with azoxymethane (AOM) is followed by cyclic treatment with DSS [65,66]. In this model, besides the genetic background of the mice, a number of other factors contribute to the development and progression of the disease.…”

“…Furthermore, both male and female mice develop DSS-induced colitis robustly; however, the males rapidly develop more significant and aggressive disease than the age-matched females. Thus, the development of DSS-induced colitis in mouse models and its severity may depend on the genetic background of mice, their gut microbiome composition, sex, and sex hormone levels [65][66][67].…”

“…As noted above and by others [13], the genetic background and sex-dependent alterations in colonization by microbes in inflamed gut of mice could alter serum levels of sex hormones and influence the composition of gut microbiome [65][66][67]. Because sex hormone levels are predicted to influence the ratio between p202 and Aim2 protein levels in colon epithelial and stem cells [26,55,72], additional studies will be needed to identify the molecular mechanisms through which Aim2 deficiency in the male and female mice renders them more susceptible to the development of CAC in the AOM/DSS mouse model.…”

Brown seaweeds protect against azoxymethane-induced hepatic repercussions through up-regulation of peroxisome proliferator-activated receptor gamma and attenuation of oxidative stress

“…Azoxymethane (AOM), a metabolite of 1,2-dimethylhydrazine (DMH), is a colon cancer inducing agent, which serves as a tool to evaluate colon tumour in rats and mice (Chan et al 2006). AOM has likewise been utilized as a part of the investigation of the preventive efficacy of numerous natural products on colon cancer (De Robertis et al 2011). It has been reported that the liver and lungs are the most affected organs during colon cancer induction using AOM (Chan et al 2006).…”

Endothelin-2 Differential Expression in Normal and Early-Stages of Colon Cancer Development

“…Adult male BALB/c mice were intraperitoneal injected with Azoxymethane (AOM)10 mg/Kg body weight and a week later, Dextran Sodium Sulphate (DSS) was given in the drinking water for seven days following the procedure reviewed by Rosenberg et al (2009) [12], Tanaka (2009) [13] and De Robertis et al, (2011) [14]. Control animal were injected with saline solution and were not given DSS.…”