Dietary copper affects azoxymethane-induced intestinal tumor formation and protein kinase C isozyme protein and mRNA expression in colon of rats

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 [micro]g 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 [alpha] protein expression in normal but not in tumor tissue. In contrast, 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. These results along with previous observations suggest that dietary copper-mediated changes in PKC [alpha], [delta] and [zeta] protein expression are not as important for colon tumor promotion/progression as they are for tumor initiation. J. Nutr. 132: 1018-1025, 2002. KEY WORDS: * colon cancer * protein kinase C * copper * rats