Submitted to: Journal of Federation of American Societies for Experimental Biology
Publication Type: Abstract Only
Publication Acceptance Date: 12/10/1999
Publication Date: 3/15/2000
Citation: Davis, C.D., Johnson, W.T. 2000. Dietary copper and dimethylhydrazine (DMH) affect protein kinase C (PKC) isozyme expression in rat colon [abstract]. The Federation of American Societies for Experimental Biology Journal. 14:A169. Interpretive Summary:
Technical Abstract: Low dietary copper has been shown to decrease the expression of various PKC isozymes and increase the risk of colon cancer development in experimental animals. Decreased expression of various PKC isozymes has also been linked to the pathogenesis of colon cancer. The purpose of this study was to investigate the relationship between dietary copper and carcinogen administration on PKC isozyme expression and aberrant crypt foci (ACF) formation (a preneoplastic lesion for colon cancer) in 88 weanling rats fed two concentrations of copper (0.9 and 7.7 ug/g diet) in an AIN-93 based diet. The rats were injected twice with either DMH or saline (25 mg/kg, i.p.) and killed at 2 time points (1 wk and 11 wk after DMH). Ingestion of low dietary copper significantly (p<0.005) increased the formation of DMH-induced ACF (116.8 vs. 59.6). Western blot analysis revealed that low dietary copper significantly (p<0.05) decreased the expression of PKC alpha, PKC delta and PKC zeta at 1 wk but not at 11 wk. At both time points, animals fed the low copper diets had significantly (p<0.0005) decreased ceruloplasmin activities, hemoglobin, hematocrit and liver copper, plasma copper and colon copper concentrations. DMH administration significantly (p<0.05) decreased the expression of PKC alpha at both time points, and decreased PKC delta and PKC zeta expression at 11 wk. Rats given DMH had significantly (p<0.05) lower final weights, and colon copper and zinc concentrations but significantly (p<0.05) higher plasma copper concentrations than saline injected animals. Neither dietary copper nor DMH treatment affected p53 expression. These results suggest that alterations in PKC expression may be related to increased susceptibility of copper-deficient animals to ACF formation.