Dietary copper and dimethylhydrazine affect protein kinase C isozyme protein and mRNA expression and the formation of aberrant crypts in colon of rats.
Low dietary copper has been shown to decrease the expression of various protein kinase C (PKC) isozymes and increase the risk of colon cancer development in experimental animals. The purpose of this study was to investigate the relationship between dietary copper and carcinogen administration on PKC isozyme accumulation and aberrant crypt foci (ACF) formation in rats fed 0.9 and 7.7 microg Cu/g diet. After 24 and 31 d on the diets, the rats were injected with either dimethylhydrazine (DMH) (25 mg/kg i.p.) or saline and killed at two time points (2 wk and 8 wk after DMH). Rats fed low dietary copper had significantly lower (p<0.0001) hematocrits, hemoglobin, ceruloplasmin activity and plasma and liver copper concentrations than rats fed adequate dietary copper. Ingestion of low dietary copper significantly (p<0.005) increased the formation of DMH-induced ACF (116.8 vs 59.6). Low dietary copper significantly (p<0.05) decreased the concentration of PKC alpha, delta, and zeta in the colon at 2 wk but not at 8 wk. Thus, changes in PKC isoform protein concentration may be related to increased susceptibility of copper-deficient animals to colon cancer.
Davis
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United States Department of Agriculture, Agricultural Research Service, Grand Forks Human Nutrition Research Center, Grand Forks, ND 58202-9034, USA. cdavis@gfhnrc.ars.usda.gov
Johnson
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D000818:Animals; D002273:Carcinogens / Q000494:pharmacology*; D003106:Colon / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D003110:Colonic Neoplasms / Q000209:etiology / Q000473:pathology; D003300:Copper / Q000008:administration & dosage* / Q000032:analysis / Q000172:deficiency; D004032:Diet; D004127:Dimethylhydrazines / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000737:chemistry; D008297:Male; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D020133:Reverse Transcriptase Polymerase Chain Reaction
D002273:Carcinogens; D004127:Dimethylhydrazines; D007527:Isoenzymes; D012333:RNA, Messenger; D003300:Copper; D011493:Protein Kinase C