title: Beef meat promotion of dimethylhydrazine-induced colorectal carcinogenesis biomarkers is suppressed by dietary calcium.
abstract: Red meat consumption is associated with increased risk of colorectal cancer. We have previously shown that haemin, Hb and red meat promote carcinogen-induced preneoplastic lesions: aberrant crypt foci (ACF) and mucin-depleted foci (MDF) in rats. We have also shown that dietary Ca, antioxidant mix and olive oil inhibit haemin-induced ACF promotion, and normalize faecal lipoperoxides and cytotoxicity. Here we tested if these strategies are effective also against red meat promotion in dimethylhydrazine-induced rats. Three diets with 60 % beef meat were supplemented with calcium phosphate (31 g/kg), antioxidant agents (rutin and butylated hydroxyanisole, 0.05 % each) and olive oil (5 %). ACF, MDF, faecal water cytotoxicity, thiobarbituric acid reactive substances (TBARS) and urinary 1,4-dihydroxynonane mercapturic acid (DHN-MA) were measured. Beef meat diet increased the number of ACF (+30 %) and MDF (+100 %) (P < 0.001), which confirms our previous findings. Promotion was associated with increased faecal water TBARs ( x 4) and cytotoxicity ( x 2), and urinary DHN-MA excretion ( x 15). Ca fully inhibited beef meat-induced ACF and MDF promotion, and normalized faecal TBARS and cytotoxicity, but did not reduce urinary DHN-MA. Unexpectedly, high-calcium control diet-fed rats had more MDF and ACF in the colon than low-Ca control diet-fed rats. Antioxidant mix and olive oil did not normalize beef meat promotion nor biochemical factors. The results confirm that haem causes promotion of colon carcinogenesis by red meat. They suggest that Ca can reduce colorectal cancer risk in meat-eaters. The results support the concept that toxicity associated with the excess of a useful nutrient may be prevented by another nutrient.
authors.affiliation: UMR1089 Xénobiotiques, INRA-ENVT, 23 ch Capelles, Toulouse, France. f.pierre@envt.fr
authors.forename: Fabrice
authors.initials: F
authors.lastname: Pierre
authors.forename: Raphaëlle
authors.initials: R
authors.lastname: Santarelli
authors.forename: Sylviane
authors.initials: S
authors.lastname: Taché
authors.forename: Françoise
authors.initials: F
authors.lastname: Guéraud
authors.forename: Denis E
authors.initials: DE
authors.lastname: Corpet
mesh_terms: D019813:1,2-Dimethylhydrazine; D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000652:urine; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D001835:Body Weight / Q000187:drug effects; D002136:Calcium, Dietary / Q000627:therapeutic use*; D002417:Cattle; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D004032:Diet; D004435:Eating / Q000187:drug effects; D005243:Feces / Q000737:chemistry; D005260:Female; D006418:Heme / Q000378:metabolism; D008460:Meat / Q000009:adverse effects*; D000069463:Olive Oil; D010938:Plant Oils / Q000627:therapeutic use; D051381:Rats; D011916:Rats, Inbred F344; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: C501116:1,4-dihydroxynonene mercapturic acid; D000975:Antioxidants; D002136:Calcium, Dietary; D000069463:Olive Oil; D010938:Plant Oils; D017392:Thiobarbituric Acid Reactive Substances; D006418:Heme; D019813:1,2-Dimethylhydrazine; D000111:Acetylcysteine