Submitted to: Journal of Federation of American Societies for Experimental Biology
Publication Type: Abstract Only
Publication Acceptance Date: 12/1/2001
Publication Date: 3/20/2002
Citation: Davis, C.D., Johnson, W.T. 2002. Low dietary copper (Cu) but not low dietary zinc (Zn) affects protein kinase C and alpha (PKC) expression in rat colon and dimethylhydrazine-induced aberrant crypt foci (ACF) formation [abstract]. The Federation of American Societies of Experimental Biology Journal. 16:A374-A375.
Technical Abstract: Decreased expression of various PKC isozymes has been linked to the development of colon cancer. Low dietary Cu has been shown to decrease the expression of PKC isozymes and increase the risk of colon cancer development in rats. Although PKC is a Zn containing protein, the effect of dietary Zn on PKC expression and colon cancer susceptibility is unknown. In the first study, 108 weanling, male Fischer-344 rats were fed two concentrations of Cu (0.9 and 5.2 ug/g diet) and 2 concentrations of Zn (5.6 and 40.3 ug/g diet) in an AIN-93 based diet. Ingestion of low dietary Cu significantly (p<0.003) increased the formation of DMH-induced ACF (258+/-22 vs 193+/-19) and decreased PKC alpha protein expression in both the cytosolic and homogenate fractions. Dietary Zn had no effects on ACF formation or on PKC expression. In the next study, 80 rats were fed diets containing either 0.8 or 5.3 ug Cu/g diet. Rats fed the low Cu diet had a significantly (p<0.0001) higher azoxymethane-induced small intestinal and total tumor incidence but no change in colon tumor incidence compared to rats fed adequate dietary Cu. Low dietary Cu significantly (p<0.004) decreased PKC alpha protein expression in normal but not in tumor tissue. These results suggest that dietary Zn does not affect colon cancer susceptibility and that dietary Cu mediated changes in PKC alpha expression are not as important for colon tumor promotion/progression as they are for tumor initiation.