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High susceptibility to azoxymethane‐induced colorectal carcinogenesis in obese KK‐ A y mice
Author(s) -
Teraoka Naoya,
Mutoh Michihiro,
Takasu Shinji,
Ueno Toshiya,
Nakano Katsuya,
Takahashi Mami,
Imai Toshio,
Masuda Shuichi,
Sugimura Takashi,
Wakabayashi Keiji
Publication year - 2010
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.25711
Subject(s) - azoxymethane , aberrant crypt foci , colorectal cancer , leptin , medicine , carcinogenesis , adenocarcinoma , endocrinology , crypt , angiogenesis , obesity , cancer , cancer research , colonic disease
Obesity is associated with colon carcinogenesis. However, not much information is available regarding the mechanisms of obesity‐associated colorectal cancer, and there are only few useful animal models for investigating the underlying mechanism between obesity and colorectal cancer. KK‐ A y mice exhibit severe obesity. Amount of visceral fat assessed by micro‐computed tomography was almost 15 times higher than that of same aged C57BL/6J mice. Treatment with azoxymethane (AOM; 200 μg/mouse injected once a week for 3 times) resulted in markedly increased colon aberrant crypt foci (ACF) development (≈70 ACF/mouse) in KK‐ A y mice compared with lean C57BL/6J mice (≈9 ACF/mouse). Moreover, administration of AOM at a dose of 200 μg/mouse once a week for 6 times developed colorectal adenocarcinomas within only 7 weeks after the last AOM injection. The incidence of adenocarcinoma was 88% in KK‐ A y mice and was markedly higher than the 4% observed in C57BL/6J mice. The number of tumors/mouse was 7.80 in KK‐ A y mice and also markedly higher than the 0.12 in the C57BL/6J case. Interestingly, adenocarcinomas were observed in most of the AOM‐treated KK‐ A y mice along with remarkable tumor angiogenesis, and some showed submucosal invasion. These results indicate that the KK‐ A y mouse, featuring intact leptin and leptin receptor Ob‐Rbl, could be a useful animal model to investigate obesity‐associated cancer.