Suppression by calcium and α-tocopherol of cured meat promotion of faecal biomarkers in human and rat is associated to protection against promotion of dimethylhydrazine-induced mucin-depleted foci in rat colons
Résumé
Epidemiology suggests that processed and red meat intake is associated with colorectal cancer risk. We have previously shown that beef, a model of cured meat, and freeze-dried ham promote carcinogen-induced preneoplasic lesions such as MDF (mucin depleted foci) in rats. We have also shown that calcium carbonate supplementation in diet inhibits beef meat promotion, and normalizes fecal lipoperoxydes and cytotoxicity, two biomarkers of heme-induced promotion. Here we tested if cured meat modulates biomarkers also in Human, and if supplementations in cured meat based-diet or directly in cured meat are efficient to protect against processed meat promotion. In a 14-day study we tested dietary compounds on their capacity to modulate fecal and urinary biomarkers. Calcium carbonate (150µmol/g) and inulin (4.5%) were added in diet. Rutin (0.1%), carnosin (0.07%), trisodique pyrophosphate (0.8%) and α-tocopherol (0.05%) were added during meat processing. The analyses of modulation of the biomarkers lead us to select calcium carbonate and α-tocopherol. These two compounds were given for 100 d to rats pretreated with dimethylhydrazine and to human volunteers in a cross-over study. Colons of rats were scored for preneoplasic lesions (ACF and MDF) and faecal and urinary biomarkers (TBARS, NOCs, Cytotoxicity) were measured in rats and Humans. Processed meat increased faecal biomarkers in Human. Calcium carbonate and α-tocopherol supplementations significantly decreased the number of MDF/colon (p=0.01). Calcium carbonate supplementations significantly decreased the fecal biomarkers (NOCs and TBARs) in rats and Humans, α-tocopherol significantly decreased NOCs in rats and TBARs in Humans. This study is the first demonstration that a short term consumption of processed meat in Human is sufficient to modulate biomarkers associated to colon carcinogenesis promotion, suggesting a risk of promotion in Human. Furthermore, we suggest that calcium supplementation in diet and α-tocopherol supplementations in cured meat might reduce colorectal cancer risk in cured meat-eaters.