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Carcinogenesis Advance Access published online on August 2, 2006

Carcinogenesis, doi:10.1093/carcin/bgl127
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© The Author 2006. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org
Received August 8, 2005
Revised June 13, 2006
Accepted June 13, 2006

CANCER BIOLOGY

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

F. Pierre 1 *, S. Tache 1, F. Guéraud 2, A. L. Rerole 1, M.-L. Jourdan 3, and C. Petit 1

1 Ecole Nationale Vétérinaire Toulouse, UMR INRA-ENVT Xénobiotiques, 23 chemin des Capelles, 31076 Toulouse, France
2 Institut National de la Recherche Agronomique, UMR INRA-ENVT Xénobiotiques, 180 chemin de Tournefeuille, 31931 Toulouse, France
3 Inserm E 0211, Nutrition Croissance et Cancer, 10 Boulevard Tonnellé, 37032 Tours Cedex, France

* To whom correspondence should be addressed.
F. Pierre, E-mail: f.pierre{at}envt.fr


   Abstract

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.

Keywords: Colorectal carcinogenesis; haem; Apc gene; faecal water; lipid peroxidation.
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