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Nutrition and Cancer

Dietary Copper Affects Azoxymethane-Induced Intestinal Tumor Formation and Protein Kinase C Isozyme Protein and mRNA Expression in Colon of Rats^{1 ,2}

U.S. Department of Agriculture, Agricultural Research Service, Grand Forks Human Nutrition Research Center, Grand Forks, ND 58202-9034

³To whom correspondence should be addressed. E-mail: cdavis{at}gfhnrc.ars.usda.gov.

Previous studies have show 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 this 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 µg Cu/g diet. After 24 and 31 d of diet consumption, 30 rats/diet were administered azoxymethane (15 mg/kg i.p.) and 10 rats/diet were administered saline. Rats continued to consume their respective diets for an additional 38 wk. Rats injected with azoxymethane and fed the low copper diet had a significantly (P < 0.0001) greater small intestinal and total tumor incidence compared with rats fed adequate dietary copper. However, dietary copper did not affect colon tumor incidence. Low dietary copper significantly (P < 0.004) decreased PKC protein expression in normal but not in tumor tissue. In contrast, low dietary copper did not affect PKC or protein expression in either the normal or tumor tissue. PKC and protein and mRNA expression were lower in tumor tissue than in normal tissue. These results along with previous observations suggest that dietary copper-mediated changes in PKC , and protein expression are not as important for colon tumor promotion/progression as they are for tumor initiation.

KEY WORDS: • colon cancer • protein kinase C • copper • rats

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