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

TLDR

The authors developed a rapid colitis‑related colon cancer model by administering a single intraperitoneal dose of azoxymethane followed by a one‑week oral course of 2 % dextran sodium sulfate to male Crj:CD‑1 mice under various protocols. At 20 weeks, the model produced 100 % adenocarcinoma incidence (5.6 ± 2.4 lesions per mouse) and 38 % adenoma incidence (0.2 ± 0.4 lesions per mouse), with lesions expressing β‑catenin, COX‑2, and iNOS but lacking p53, demonstrating that a single week of 2 % DSS after low‑dose AOM strongly promotes colon tumorigenesis in male ICR mice.

Abstract

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 β‐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.