Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/14/2002
Publication Date: 5/1/2004
Citation: Davis, C.D., Johnson, W.T. 2002. Dietary copper affects azoxymethane-induced intestinal tumor formation and protein kinase C isozyme protein and MRNA expression in colon of rats. Journal of Nutrition. 132:1018-1025.
Interpretive Summary: Colon cancer is the second leading cause of cancer deaths in the United States and the fourth most common cause of cancer deaths worldwide. Low dietary copper has been shown to increase the risk of development of precancerous lesions for colon cancer in experimental animals and to decrease the expression of various protein kinase C isozymes. Protein kinase C is a series of proteins involved in the signal transduction pathway within the cell. The current study investigated the relationship between dietary copper and carcinogen administration on protein kinase C expression and the appearance of intestinal tumors. Low dietary copper increased the formation of small intestinal tumors and total intestinal tumors but not colon tumors compared to rats fed adequate dietary copper. However, dietary copper mediated changes in protein kinase C expression did not appear to be important for the effect of dietary copper on intestinal tumor formation. These results have practical implications because many o the diets consumed in the United States do not contain the recommended amount of copper.
Technical Abstract: Previous studies have shown that changes in protein kinase C (PKC) isoform expression may be related to increased susceptibility of copper-deficient rats to aberrant crypt formation. The purpose of the current study was to determine whether dietary copper would affect azoxymethane-induced intestinal tumor formation and PKC isozyme expression in normal colonic mucosa and tumor samples. Eighty weanling Fischer-344 rats were randomly assigned to diets that contained either 0.8 or 5.3 ug Cu/g diet. After 24 and 31 d on the diets, 30 rats/diet were administered azoxymethane (15 mg/kg i.p.) and 10 rats/diet were administered saline. Rats fed the low copper diet had a significantly (p<0.0001) higher small intestinal and total tumor incidence but no change in colon tumor incidence compared to rats fed adequate dietary copper. Low dietary copper significantly (p<0.004) decreased PKC alpha protein expression in normal but not tumor tissue. However, low dietary copper did not affect PKC delta or zeta protein expression in either the normal or tumor tissue. PKC alpha and delta protein and mRNA expression were lower in tumor tissue than in normal tissue. This suggests that dietary copper mediated changes in PKC alpha, delta and zeta protein expression are not important for colon tumor formation.