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Carcinogenesis

Title:		Red meat and colorectal cancer: Nrf2-dependent antioxidant response contributes to the resistance of preneoplastic colon cells to fecal water of hemoglobin- and beef-fed rats
Author(s):		Surya R; Helies-Toussaint C; Martin OC; Gauthier T; Gueraud F; Tache S; Naud N; Jouanin I; Chantelauze C; Durand D; Joly C; Pujos-Guillot E; Pierre FH; Huc L;
Address:		"Toxalim, Universite de Toulouse, INRA, INP-ENVT, INP-EI-Purpan, Universite de Toulouse 3 Paul Sabatier, 180 chemin de Tournefeuille, F-31027 Toulouse, France. Universite de Toulouse III, INP, ENVT, UPS, TOXALIM, F-31027 Toulouse, France. INRA, UMR1213 Herbivores, F-63112 Saint-Genes-Champanelle, France. Universite de Lyon - VetAgro Sup, UMR1213 Herbivores, F-69280 Marcy l'Etoile, France. INRA, UMR1019, Plateforme d'Exploration du Metabolisme, F-63000 Clermont-Ferrand, France and. INRA, UMR1019, UNH, F-63000 Clermont-Ferrand, France"
Journal Title:		Carcinogenesis
Year:		2016
Volume:		20160318
Issue:		6
Page Number:		635 - 645
DOI:		10.1093/carcin/bgw035
ISSN/ISBN:		1460-2180 (Electronic) 0143-3334 (Linking)
Abstract:		"Epidemiological studies have associated red meat intake with risk of colorectal cancer. Experimental studies explain this positive association by the oxidative properties of heme iron released in the colon. This latter is a potent catalyst for lipid peroxidation, resulting in the neoformation of deleterious aldehydes in the fecal water of heme-fed rats. The toxicity of fecal water of heme-fed rats was associated to such lipid peroxidation. This study demonstrated that fecal water of hemoglobin- and beef-fed rats preferentially induced apoptosis in mouse normal colon epithelial cells than in those carrying mutation on Apc (Adenomatous polyposis coli) gene, considered as preneoplastic. Highlighting the importance of lipid peroxidation and neoformation of secondary aldehydes like 4-hydroxy-2-nonenal (HNE), we optimized the depletion of carbonyl compounds in the fecal water which turned out to abolish the differential apoptosis in both cell lines. To explain the resistance of preneoplastic cells towards fecal water toxicity, we focused on Nrf2, known to be activated by aldehydes, including HNE. Fecal water activated Nrf2 in both cell lines, associated with the induction of Nrf2-target genes related to aldehydes detoxification. However, the antioxidant defense appeared to be higher in preneoplastic cells, favoring their survival, as evidenced by Nrf2 inactivation. Taken together, our results suggest that Nrf2-dependent antioxidant response was involved in the resistance of preneoplastic cells upon exposure to fecal water of hemoglobin- and beef-fed rats. This difference could explain the promoting effect of red meat and heme-enriched diet on colorectal cancer, by initiating positive selection of preneoplastic cells"
Keywords:		"Aldehydes Animals Antioxidants/*metabolism Apoptosis Colon/metabolism/pathology Colorectal Neoplasms/*etiology Feces Hemoglobins/*pharmacology Inactivation, Metabolic Male Mice NF-E2-Related Factor 2/genetics/*metabolism Precancerous Conditions/metabolism;"
Notes:		"MedlineSurya, Reggie Helies-Toussaint, Cecile Martin, Oceane C Gauthier, Thierry Gueraud, Francoise Tache, Sylviane Naud, Nathalie Jouanin, Isabelle Chantelauze, Celine Durand, Denys Joly, Charlotte Pujos-Guillot, Estelle Pierre, Fabrice H Huc, Laurence eng Research Support, Non-U.S. Gov't England 2016/03/20 Carcinogenesis. 2016 Jun; 37(6):635-645. doi: 10.1093/carcin/bgw035. Epub 2016 Mar 18"