Heme iron amplifies azoxymethane initiating effect on rat colon preneoplastic lesions
Résumé
Objective Colorectal cancer is a major public health issue for which dietary factors such as red and processed meat consumption seem to play a prominent role. Heme iron, which is present in important concentration in those food products, was reported to play a role in colorectal cancer promotion in animal studies. However, its role in colorectal cancer initiation remains to be established. Methods Male Fischer 344 rats were given experimental diets (control diet, ferric citrate-supplemented diet or hemin-supplemented diet) for 2 weeks before being initiated for colon cancer with azoxymethane. Rats were then fed a control diet for 8 weeks. Preneoplastic lesions, lipid peroxidation, genotoxicity and oxidative stress markers, together with gut microbiota, were analyzed. Results Heme iron, given in the rat diet for only 2 weeks before the colorectal cancer initiating event, increased two types of preneoplastic lesions in the rat colon, namely aberrant crypt foci and mucin-depleted foci, when compared to a control diet containing the same amount of iron in a non-heminic form. This heme iron concentration in the diet, representative of human consumption, induced at the same time a huge increase in luminal lipid peroxidation, a significant increase in RNA/DNA oxidative damage and an increase in the expression of antioxidant defenses in colon mucosa, accompanied by epithelial cell proliferation together with a reduction in colon mucus cells, and a gut dysbiosis. Conclusion These results, obtained in an animal model, suggest that iron, only in its heminic form, has a co-initiating effect on colorectal carcinogenesis. Significance statement Heme iron from red meat could play a role in colon cancer initiation in addition to its promoting effect.
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