1. Calcium and α-tocopherol suppress cured-meat promotion of chemically induced colon carcinogenesis in rats and reduce associated biomarkers in human volunteers.
- Author
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Pierre FH, Martin OC, Santarelli RL, Taché S, Naud N, Guéraud F, Audebert M, Dupuy J, Meunier N, Attaix D, Vendeuvre JL, Mirvish SS, Kuhnle GC, Cano N, and Corpet DE
- Subjects
- Abietanes administration & dosage, Acetylcysteine urine, Adult, Aged, Animals, Biomarkers blood, Blood Glucose analysis, C-Reactive Protein analysis, C-Reactive Protein metabolism, Carcinogenesis chemically induced, Carcinogens toxicity, Cholesterol blood, Colon pathology, Colorectal Neoplasms drug therapy, Colorectal Neoplasms prevention & control, Creatinine blood, Cross-Over Studies, Dimethylhydrazines administration & dosage, Dimethylhydrazines adverse effects, Diphosphates administration & dosage, Feces chemistry, Female, Healthy Volunteers, Humans, Inulin administration & dosage, Middle Aged, Rats, Rats, Inbred F344, Rutin administration & dosage, Single-Blind Method, Thiobarbituric Acid Reactive Substances analysis, Thiobarbituric Acid Reactive Substances metabolism, Calcium, Dietary administration & dosage, Carcinogenesis pathology, Colon drug effects, Meat Products adverse effects, alpha-Tocopherol administration & dosage
- Abstract
Background: Processed meat intake has been 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: We investigated 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 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 14 d, and fecal biomarkers were measured. On the basis of these results, calcium and tocopherol were kept for the following additional 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 crossover study (180 g/d for 4 d). Rat colons were scored for mucin-depleted foci, putative precancer lesions. Biomarkers of nitrosation, lipoperoxidation, and cytotoxicity were measured in the urine and feces of rats and volunteers., Results: Cured meat increased nitroso compounds and lipoperoxidation in human stools (both P < 0.05). Calcium normalized both biomarkers in rats and human feces, whereas tocopherol only decreased nitro compounds in rats and lipoperoxidation in feces of volunteers (all P < 0.05). Last, calcium and tocopherol reduced the number of mucin-depleted foci per colon in rats compared with nonsupplemented cured meat (P = 0.01)., Conclusion: Data suggest that the addition of calcium carbonate to the diet or α-tocopherol to cured meat may reduce colorectal cancer risk associated with cured-meat intake. This trial was registered at clinicaltrials.gov as NCT00994526.
- Published
- 2013
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