Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA, 94720, USA,
Pathol Oncol Res. 2013 Oct;19(4):657-66. doi: 10.1007/s12253-013-9626-0. Epub 2013 Mar 28.
A large body of epidemiological data indicates that obesity increases the risk of colon cancer in humans. There are limited studies using rodent models where the relationship between obesity and colon cancer has been studied. In this study, wild-type diet-induced obese (DIO) mice and lean wild-type controls were used to investigate the influence of obesity on the risk of colon cancer. We hypothesized that the obese phenotype would exhibit increased colonic tumorigenesis. Colon cancer was chemically induced by injecting the mice with azoxymethane (AOM) at levels that we experimentally determined to result in equivalent AOM concentrations in circulating blood. Risk of colon cancer was assessed via microscopic examination of entire colons for aberrant crypts, aberrant crypt foci and proliferation levels. The DIO mice were found to have significantly more aberrant crypts and aberrant crypt foci as well as increased proliferation of colonocytes per mouse compared to wild-type control mice, supporting the epidemiological data that obesity increases the risk of colonic tumorigenesis.
大量的流行病学数据表明,肥胖会增加人类患结肠癌的风险。使用啮齿动物模型进行的研究有限,这些研究探讨了肥胖与结肠癌之间的关系。在这项研究中,使用野生型饮食诱导肥胖(DIO)小鼠和瘦野生型对照小鼠来研究肥胖对结肠癌风险的影响。我们假设肥胖表型会表现出结肠肿瘤发生的增加。通过向小鼠注射偶氮甲烷(AOM)来化学诱导结肠癌,我们实验确定了注射的 AOM 水平可使循环血液中的 AOM 浓度达到等效。通过对整个结肠进行显微镜检查以评估异常隐窝、异常隐窝灶和增殖水平来评估结肠癌的风险。与野生型对照小鼠相比,DIO 小鼠的异常隐窝和异常隐窝灶明显更多,并且每个小鼠的结肠细胞增殖增加,这支持了肥胖会增加结肠肿瘤发生风险的流行病学数据。