Carcinogenesis Advance Access published online on September 30, 2004
Carcinogenesis, doi:10.1093/carcin/bgh292
© 2004 by Oxford University Press
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1 The Oncologic Pathology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 920-0293
Heterocyclic amines are known to be important environmental carcinogens in several organs including colon. Because a lack of sufficient animal models using these for colon carcinogenesis, the aim of this study was to induce colonic epithelial malignancies within a short-term period and analyze the expression of cycooxygenase-2, inducible nitric oxide synthase and
Revised September 15, 2004
Accepted September 17, 2004
CARCINOGENESIS
Colonic adenocarcinomas rapidly induced by the combined treatment with 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and dextran sodium sulfate in male ICR mice possess
-catenin gene mutations and increases immunoreactivity for -catenin, cyclooxygenase-2, and inducible nitric oxide synthase
2 The Oncologic Pathology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 920-0293; Resarch Fellow of the Japan Science for the Promotion of Science, National Cancer Research Institute, 5-1-1 Tsukiji, Chuoku, Tokyo 104-0045, Japan
3 Cancer Prevention Basic Research Project, National Cancer Research Institute, 5-1-1 Tsukiji, Chuoku, Tokyo 104-0045, Japan
Abstract 
-catenin, and mutation of -catenin gene in induced tumors. Male ICR mice were given a single intragastric administration (200 mg/kg body weight) of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine or 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, and followed by 2% dextran sodium sulfate in drinking water for a week. The expression of -catenin, cyclooxygenase-2 and inducible nitric oxide synthase was immunohistochemically assessed in colonic epithelial lesions and the -catenin gene mutations in colonic adenocarcinomas induced were analyzed by the single strand conformation polymorphism method, restriction enzyme fragment length polymorphism and direct sequencing. At week 16, a high incidence of colonic neoplasms with dysplastic lesions developed in mice received 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and dextran sodium sulfate, but a few in those given 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline and dextran sodium sulfate Immunohistochemically, the adenocarcinomas induced were all positive for three proteins. All 7 adenocarcinomas induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and dextran sodium sulfate have mutations. The findings suggest that dextran sodium sulfate exerts a powerful tumor-promoting effects on 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine-initiated colon carcinogenesis in mice and this mouse model is useful for investigating environment-related colon carcinogenesis within a short-term period.-Catenin.
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