Table 1.
Common mouse models of colitis-associated carcinogenesis. For more detailed reviews on mouse models of IBD see [261–263].
| Model | Specification | Mechanism | Reference |
|---|---|---|---|
| DSS | Chemical-induced (Supplementation of drinking water) |
Disruption of the epithelial barrier. DSS polymers are not genotoxic, but directly toxic to colonic epithelial cells of the basal crypts. Protocols exist for acute and chronic colitis. Colitis induced within 2 (acute) to 8 (chronic) weeks. Development of dysplasia and colon cancers requires several months. In the acute phase inflammation is mainly driven by innate immunity. | [264] |
| DSS + AOM | Chemical-induced (Supplementation of drinking water) |
Carcinogen-induced. Initial dose of AOM in combination with DSS. Bioactivation of AOM to mutagenic methyldiazonium ion. Tumor formation within 10 weeks. Useful to study the role of inflammation after carcinogen-induced tumor-initiation. | [265] |
| TNBS in ethanol | Chemical-induced (intrarectal administration) |
Hapten-induced hypersensitivity. Activation of a T-cell-mediated response against hapten-modified autologous proteins/luminal antigens. Protocols for acute and chronic colitis. Colitis induced within 2 weeks. Inflammation dependent on innate and adaptive immunity (Th1- and Th17-type). | [264] |
| Il-10−/− mice | Genetic | Disruption of anti-inflammatory signaling. Mild disease progression. Development of a spontaneous CD4+ Th1-driven enterocolitis. Dependent on IFN-γ in the initial phase and Il12 for disease progression. Development of adenocarcinoma after ~6 months. | [266,267] |
| Gpx1/2−/− mice | Genetic | Interference with antioxidant response. GPx1/2 detoxify H2O2 by glutathione oxidation. Development of ileocolitis between 2–7 weeks of age. Dysplasia and adenocarcinoma after ~4 months. | [120] |
| H.h.-infected Rag2−/−mice | Genetic + infection | Lack of adaptive immunity causes disturbed pathogen response. Induction of chronic typhlocolitis 10 weeks p.i. with first occurrence of colon carcinomas 20 weeks p.i. Since Rag2−/− mice lack adaptive immunity, inflammation is driven by innate immunity. | [25–28] |
AOM, azoxymethane; DSS, dextran sodium sulfate; TNBS, 2,4,6-trinitro benzene sulfonic acid; GPx, glutathione peroxidase; H.h., Helicobacter hepaticus; p.i., post infection.