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Meat and cancer: haemoglobin and haemin in a low calcium diet promote colorectal carcinogenesis at the aberrant crypt stage in rats

Pierre, Fabrice and Taché, Sylviane and Petit, Claude and Van der Meer, Roleof and Corpet, Denis E. Meat and cancer: haemoglobin and haemin in a low calcium diet promote colorectal carcinogenesis at the aberrant crypt stage in rats. (2003) Carcinogenesis. 1683-1690.

(Document in English)

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Official URL: http://carcin.oxfordjournals.org/cgi/reprint/24/10/1683


High intake of red meat, but not of white meat, is associated with an increased risk of colon cancer. However, red meat does not promote cancer in rodents. Haemin, added to low-calcium diets, increases colonic proliferation, and haemoglobin, added to high-fat diets, increases the colon tumour incidence in rats, an effect possibly due to peroxyl radicals. We thus speculated that haem might be the promoting agent in meat, and that prevention strategies could use calcium and antioxidants. These hypotheses were tested in rats at the aberrant crypt foci (ACF) stage at 100 days. F344 rats (n = 124) were given an injection of azoxymethane and were then randomized to 11 groups fed with low-calcium (20 micro mol/g) AIN76-based diets, containing 5% safflower oil. Haemin (0.25, 0.5 and 1.5 micro mol/g) or haemoglobin (1.5 and 3 micro mol haem/g) was added to five experimental diets, compared with a control diet without haem. Three other high-haemin diets (1.5 micro mol/g) were supplemented with calcium (250 micro mol/g), antioxidant butylated hydroxyanisole and rutin (0.05% each), and olive oil, which replaced safflower oil. Faecal water was assayed for lipid peroxidation by thiobarbituric acid reactive substances (TBARs) test, and for cytolytic activity. Haemin strikingly increased the ACF size, dose-dependently, from 2.6 to 11.4 crypts/ACF (all P < 0.001). The high-haemin diet also increased the number of ACF per colon (P < 0.001). Promotion was associated with increased faecal water TBARs and cytotoxicity. Calcium, olive oil and antioxidants each inhibited the haemin-induced ACF promotion, and normalized the faecal TBARs and cytotoxicity. The haemoglobin diets increased the number of ACF and faecal TBARs, but not the ACF size or the faecal cytotoxicity. In conclusion, dietary haemin is the most potent known ACF promoter. Haemoglobin is also a potent promoter of colorectal carcinogenesis. The results suggest that myoglobin in red meat could promote colon cancer. Diets high in calcium, or in oxidation-resistant fats, may prevent the possible cancer-promoting effect of red meat.

Item Type:Article
Additional Information:Thanks to Oxford University Press. The definitive version is available at http://carcin.oxfordjournals.org/ The original PDF of the article can be found at Carcinogenesis website : http://carcin.oxfordjournals.org/cgi/reprint/24/10/1683
Audience (journal):International peer-reviewed journal
Uncontrolled Keywords:
Institution:French research institutions > Institut National de la Recherche Agronomique - INRA (FRANCE)
Other partners > Wageningen Centre for Food Sciences - WCFS (NETHERLANDS)
Université de Toulouse > Ecole Nationale Vétérinaire de Toulouse - ENVT (FRANCE)
Laboratory name:
Deposited On:16 Sep 2009 09:00

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