Calcium and α-Tocopherol Suppress Cured Meat Promotion of Chemically-Induced Colon Carcinogenesis in Rats and Reduce Associated Biomarkers in Human Volunteers

Abstract

Background: Processed meat intake is associated with increased colorectal cancer risk. We have shown that cured meat promotes carcinogen-induced preneoplastic lesions and increases specific biomarkers in the colon of rats. Objectives: To investigate whether cured meat modulates biomarkers of cancer risk in human volunteers, and whether specific agents can suppress cured meat induced preneoplastic lesions in rats, and associated biomarkers in rats and in humans. Design: Six additives (calcium carbonate, inulin, rutin, carnosol, α-tocopherol and trisodium pyrophosphate) were added to cured meat given to groups of rats for fourteen days, then fecal biomarkers were measured. Based on these results, calcium and tocopherol were kept for further experiments: cured meat, with or without calcium or tocopherol, was given to dimethylhydrazine-initiated rats (47% meat diet for 100 d), and to human volunteers in a cross-over study (180 g/d for 4 d). Rat colons were scored for mucin depleted foci, putative pre-cancer lesions. Biomarkers of nitrosation, lipoperoxidation, and cytotoxicity were measured in rats and volunteers’ urine and feces. Results: Cured meat increased nitroso-compounds and lipoperoxidation in humans stools (both P<0.05). Calcium normalized both biomarkers in rats and humans’ feces, while tocopherol only decreased nitro-compounds in rats and lipoperoxidation in volunteers’ feces (all p<0.05). Lastly, calcium and tocopherol reduced the number of mucin depleted foci per colon in rats compared with non supplemented cured meat (P=0.01). Conclusion: The data suggest that addition of calcium carbonate to the diet or of α-tocopherol to cured meat may reduce colorectal cancer risk associated with cured meat intake.