Apc mutation induces resistance of colonic cells to lipoperoxide-triggered apoptosis induced by faecal water from haem-fed rats.
Recent epidemiological studies suggest that high meat intake is associated with promotion of colon cancer linked with 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 [adenomatous polyposis coli (Apc)+/+] or premalignant cells (Apc-/+). 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.
Pierre
F
F
Ecole Nationale Vétérinaire Toulouse, UMR INRA-ENVT Xénobiotiques 23 chemin des Capelles, 31076 Toulouse, France. f.pierre@envt.fr
Tache
S
S
Guéraud
F
F
Rerole
A L
AL
Jourdan
M-L
ML
Petit
C
C
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001834:Body Water; D003106:Colon / Q000166:cytology / Q000187:drug effects*; D005243:Feces; D005260:Female; D017491:Genes, APC; D006418:Heme / Q000008:administration & dosage*; D008054:Lipid Peroxides / Q000494:pharmacology*; D009154:Mutation; D051381:Rats; D011916:Rats, Inbred F344
D008054:Lipid Peroxides; D006418:Heme