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Apc mutation induces resistance of colonic cells to lipoperoxide-triggered apoptosis induced by faecal water from haem-fed rats

Pierre, Fabrice and Taché, Sylviane and Guéraud, Françoise and Rerole, Anne-Laure and Jourdan, Marie-Lise and Petit, Claude Apc mutation induces resistance of colonic cells to lipoperoxide-triggered apoptosis induced by faecal water from haem-fed rats. (2006) Carcinogenesis (00). 1-7. ISSN 0143-3334

(Document in English)

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Official URL: http://carcin.oxfordjournals.org/cgi/reprint/bgl127v1


Recent epidemiological studies suggest that high meat intake is associated with promotion of colon cancer linked to haem-iron intake. We previously reported that dietary haem, in the form of either haemoglobin or meat, promotes precancerous lesions in the colon of rats given a low-calcium diet. The mechanism of promotion by haem is not known, but is associated with increased lipid peroxidation in faecal water and strong cytotoxic activity of faecal water on a cancerous mouse colonic epithelial cell line. To better understand the involvement of faecal water components of haem-fed rats in colon cancer promotion, we explored the effect of faecal water on normal (Apc +/+) or premalignant cells (Apc Min/+). Further, we tested if this effect was correlated to lipoperoxidation and 4-hydroxynonenal (HNE). We show here for the first time that heterozygote Apc mutation represents a strong selective advantage, via resistance to apoptosis induction (caspase 3 pathway), for colonic cells exposed to a haem-iron induced lipoperoxidation. The fact that HNE treatment of the cells provoked the same effects as the faecal water of rats fed the haem-rich diet suggests that this compound triggers apoptosis in those cells. We propose that this mechanism could be involved in the promotion of colon carcinogenesis by haem in vivo.

Item Type:Article
Additional Information:Author can archive pre-print after 12 month embargo. Thanks to Oxford University Press. The publisher version can be found at : http://carcin.oxfordjournals.org/cgi/reprint/bgl127v1
Audience (journal):International peer-reviewed journal
Uncontrolled Keywords:
Institution:French research institutions > Institut National de la Recherche Agronomique - INRA (FRANCE)
French research institutions > Institut National de la Santé et de la Recherche Médicale - INSERM (FRANCE)
Université de Toulouse > Ecole Nationale Vétérinaire de Toulouse - ENVT (FRANCE)
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Deposited On:18 Apr 2008 10:07

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