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.
Tanaka
Takuji
T
The First Department of Pathology, Kanazawa Medical University, Uchinada, Ishikawa 920-0293. takutt@kanazawa-med.ac.jp
Kohno
Hiroyuki
H
Suzuki
Rikako
R
Yamada
Yasuhiro
Y
Sugie
Shigeyuki
S
Mori
Hideki
H
D000230:Adenocarcinoma / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D000236:Adenoma / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000925:Anticoagulants / Q000633:toxicity; D001397:Azoxymethane / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D003092:Colitis / Q000139:chemically induced / Q000473:pathology; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D051546:Cyclooxygenase 2; D003598:Cytoskeletal Proteins / Q000378:metabolism; D016264:Dextran Sulfate / Q000633:toxicity*; D004195:Disease Models, Animal; D007249:Inflammation; D007274:Injections, Intraperitoneal; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D008407:Mast Cells / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008813:Mice, Inbred ICR; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051176:beta Catenin
D000925:Anticoagulants; C495267:CTNNB1 protein, mouse; D002273:Carcinogens; D003598:Cytoskeletal Proteins; D007527:Isoenzymes; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; D051176:beta Catenin; D016264:Dextran Sulfate; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D001397:Azoxymethane