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ARS Home » Plains Area » Grand Forks, North Dakota » Grand Forks Human Nutrition Research Center » Healthy Body Weight Research » Research » Publications at this Location » Publication #110612
Title: INADEQUATE DIETARY COPPER INCREASES TUMORIGENESIS IN THE MIN MOUSE

Author
item Davis, Cindy
item Newman Jr, Samuel

Submitted to: Carcinogenesis
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/26/2000
Publication Date: N/A
Citation: N/A

Interpretive Summary: Colon cancer is the second leading cause of cancer mortality in the United States and the fourth most common cause of cancer mortality worldwide. APC a gene known to suppress the formation of tumors is altered early on during colon cancer development. Familial adenomatous polyposis (FAP) is a disease that has been linked to changes in the APC gene known as mutations. Individuals possessing these mutations develop numerous intestinal polyps (precancerous lesions) at an early age. Min (multiple intestinal neoplasia) mice carry a mutation in what is equivalent to the human APC gene and develop intestinal tumors similar to those found in patients with familial adenomatous polyposis syndrome. Thus these mice are a good model for the investigation of the effects of dietary alterations on genetic susceptibility for intestinal cancer. The current study investigated the relationship between dietary copper and intestinal cancer susceptibility in Min mice. Mice that were fed a copper deficient diet had significantly higher small intestine tumor incidence and a significantly higher small intestine mass than animals fed adequate dietary copper. Therefore inadequate dietary copper can increase tumor development in a genetic model for human cancer. These results have practical implications because more than 80% of the diets consumed in the United States do not contain the recommended amount of copper.

Technical Abstract: Germline mutations of the adenomatous polypososis coli (APC) gene lead to multiple intestinal tumors in familial adenomatous polyposis patients and in multiple intestinal neoplasia (Min) mice. Thus these mice are a good model for the investigation of the effects of dietary alterations on genetic susceptibility for intestinal cancer. The current study investigated the relationship between dietary copper and intestinal cancer susceptibility in Min mice. When pups reached 1 week old, the nursing dams and their pups were placed on an AIN-93G diet containing either 1 or 6 ppm copper (by analysis, 0.76 and 5.49 ug Cu/g diet, respectively) until they were 13 weeks old. Animals fed copper deficient diets had a significantly (p<0.0003) higher small intestine tumor incidence and a significantly (p<0.04) higher small intestine tumor mass than animals fed adequate dietary copper. Therefore inadequate dietary copper can increase the spontaneous tumorigenesis that occurs in the Min mouse. These results have practical implications because more than 80% of the diets consumed in the United States do not contain the recommended amount of copper.