title: 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 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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Université de Toulouse, French National Institute For Agricultural Research, Joint Research Unit 1331 Xénobiotiques, Toulouse, France (FHFP, OCBM, RLS, ST, NN, FG, MA, JD, and DEC); the French Pork and Pig Institute-Institut du Porc, Paris, France (RLS and J-LV); the INRA, UMR 1019, Human Nutrition Unit, Research Center for Human Nutrition Auvergne, Clermont-Ferrrand, France (NM, DA, and NC); the University hospital Clermont-Ferrand, Service de Nutrition, Clermont-Ferrrand, France (NM and NC); the Eppley Institute for Research in Cancer, University of Nebraska Medical Center, Omaha, NE (SSM); and the Department of Food and Nutritional Sciences, University of Reading, Reading, United Kingdom (GCGK).
authors.forename: Fabrice H F
authors.initials: FH
authors.lastname: Pierre
authors.forename: Océane C B
authors.initials: OC
authors.lastname: Martin
authors.forename: Raphaelle L
authors.initials: RL
authors.lastname: Santarelli
authors.forename: Sylviane
authors.initials: S
authors.lastname: Taché
authors.forename: Nathalie
authors.initials: N
authors.lastname: Naud
authors.forename: Françoise
authors.initials: F
authors.lastname: Guéraud
authors.forename: Marc
authors.initials: M
authors.lastname: Audebert
authors.forename: Jacques
authors.initials: J
authors.lastname: Dupuy
authors.forename: Nathalie
authors.initials: N
authors.lastname: Meunier
authors.forename: Didier
authors.initials: D
authors.lastname: Attaix
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Vendeuvre
authors.forename: Sidney S
authors.initials: SS
authors.lastname: Mirvish
authors.forename: Gunter C G
authors.initials: GC
authors.lastname: Kuhnle
authors.forename: Noel
authors.initials: N
authors.lastname: Cano
authors.forename: Denis E
authors.initials: DE
authors.lastname: Corpet
mesh_terms: D045784:Abietanes / Q000008:administration & dosage; D000111:Acetylcysteine / Q000652:urine; D000328:Adult; D000368:Aged; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D002097:C-Reactive Protein / Q000032:analysis / Q000378:metabolism; D002136:Calcium, Dietary / Q000008:administration & dosage*; D063646:Carcinogenesis / Q000139:chemically induced / Q000473:pathology*; D002273:Carcinogens / Q000633:toxicity; D002784:Cholesterol / Q000097:blood; D003106:Colon / Q000187:drug effects* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000517:prevention & control; D003404:Creatinine / Q000097:blood; D018592:Cross-Over Studies; D004127:Dimethylhydrazines / Q000008:administration & dosage / Q000009:adverse effects; D011756:Diphosphates / Q000008:administration & dosage; D005243:Feces / Q000737:chemistry; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007444:Inulin / Q000008:administration & dosage; D008461:Meat Products / Q000009:adverse effects*; D008875:Middle Aged; D051381:Rats; D011916:Rats, Inbred F344; D012431:Rutin / Q000008:administration & dosage; D016037:Single-Blind Method; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis / Q000378:metabolism; D024502:alpha-Tocopherol / Q000008:administration & dosage*
chemical_list: D045784:Abietanes; D015415:Biomarkers; D001786:Blood Glucose; D002136:Calcium, Dietary; D002273:Carcinogens; D004127:Dimethylhydrazines; D011756:Diphosphates; D017392:Thiobarbituric Acid Reactive Substances; C068623:carnosol; D012431:Rutin; D007444:Inulin; D002097:C-Reactive Protein; D002784:Cholesterol; D003404:Creatinine; D024502:alpha-Tocopherol; C003319:sodium pyrophosphate; D000111:Acetylcysteine
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