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Tanaka, T. et al.

Tanaka, Kohno, Suzuki, Yamada, Sugie, Mori,

A novel inflammation-related mouse colon carcinogenesis model induced by azoxymethane and dextran sodium sulfate.

To develop an efficient animal model for colitis-related carcinogenesis, male Crj: CD-1 (ICR) mice were given a single intraperitoneal administration (10 mg/kg body weight) of a genotoxic colonic carcinogen, azoxymethane (AOM), and a 1-week oral exposure (2% in drinking water) to a non-genotoxic carcinogen, dextran sodium sulfate (DSS), under various protocols. At week 20, colonic neoplasms (adenocarcinomas, 100% incidence with 5.60 +/- 2.42 multiplicity; and adenomas, 38% incidence with 0.20 +/- 0.40 multiplicity) with dysplastic lesions developed in mice treated with AOM followed by DSS. Protocols in which AOM was given during or after DSS administration induced a few tubular adenomas or no tumors in the colon. Immunohistochemical investigation of such dysplasias and neoplasms revealed that all lesions were positive for beta-catenin, cyclooxygenase-2 and inducible nitric oxide synthase, but did not show p53 immunoreactivity. The results indicate that 1-week administration of 2% DSS after initiation with a low dose of AOM exerts a powerful tumor-promoting activity in colon carcinogenesis in male ICR mice, and may provide a novel mouse model for investigating colitis-related colon carcinogenesis and for identifying xenobiotics with modifying effects.[1]

References

A novel inflammation-related mouse colon carcinogenesis model induced by azoxymethane and dextran sodium sulfate. Tanaka, T., Kohno, H., Suzuki, R., Yamada, Y., Sugie, S., Mori, H. Cancer Sci. (2003) [Pubmed]

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