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.
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.
authors.affiliation: Toxalim, Université de Toulouse, INRA, INP-ENVT, INP-EI-Purpan, Université de Toulouse 3 Paul Sabatier, 180 chemin de Tournefeuille, F-31027 Toulouse, France.|Université de Toulouse III, INP, ENVT, UPS, TOXALIM, F-31027 Toulouse, France.
authors.forename: Reggie
authors.initials: R
authors.lastname: Surya
authors.affiliation: Toxalim, Université de Toulouse, INRA, INP-ENVT, INP-EI-Purpan, Université de Toulouse 3 Paul Sabatier, 180 chemin de Tournefeuille, F-31027 Toulouse, France.|Université de Toulouse III, INP, ENVT, UPS, TOXALIM, F-31027 Toulouse, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Héliès-Toussaint
authors.affiliation: Toxalim, Université de Toulouse, INRA, INP-ENVT, INP-EI-Purpan, Université de Toulouse 3 Paul Sabatier, 180 chemin de Tournefeuille, F-31027 Toulouse, France.|Université de Toulouse III, INP, ENVT, UPS, TOXALIM, F-31027 Toulouse, France.
authors.forename: Océane C
authors.initials: OC
authors.lastname: Martin
authors.affiliation: Toxalim, Université de Toulouse, INRA, INP-ENVT, INP-EI-Purpan, Université de Toulouse 3 Paul Sabatier, 180 chemin de Tournefeuille, F-31027 Toulouse, France.|Université de Toulouse III, INP, ENVT, UPS, TOXALIM, F-31027 Toulouse, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Gauthier
authors.affiliation: Toxalim, Université de Toulouse, INRA, INP-ENVT, INP-EI-Purpan, Université de Toulouse 3 Paul Sabatier, 180 chemin de Tournefeuille, F-31027 Toulouse, France.|Université de Toulouse III, INP, ENVT, UPS, TOXALIM, F-31027 Toulouse, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Guéraud
authors.affiliation: Toxalim, Université de Toulouse, INRA, INP-ENVT, INP-EI-Purpan, Université de Toulouse 3 Paul Sabatier, 180 chemin de Tournefeuille, F-31027 Toulouse, France.|Université de Toulouse III, INP, ENVT, UPS, TOXALIM, F-31027 Toulouse, France.
authors.forename: Sylviane
authors.initials: S
authors.lastname: Taché
authors.affiliation: Toxalim, Université de Toulouse, INRA, INP-ENVT, INP-EI-Purpan, Université de Toulouse 3 Paul Sabatier, 180 chemin de Tournefeuille, F-31027 Toulouse, France.|Université de Toulouse III, INP, ENVT, UPS, TOXALIM, F-31027 Toulouse, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Naud
authors.affiliation: Toxalim, Université de Toulouse, INRA, INP-ENVT, INP-EI-Purpan, Université de Toulouse 3 Paul Sabatier, 180 chemin de Tournefeuille, F-31027 Toulouse, France.|Université de Toulouse III, INP, ENVT, UPS, TOXALIM, F-31027 Toulouse, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Jouanin
authors.affiliation: INRA, UMR1213 Herbivores, F-63112 Saint-Genès-Champanelle, France.|Université de Lyon - VetAgro Sup, UMR1213 Herbivores, F-69280 Marcy l'Etoile, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Chantelauze
authors.affiliation: INRA, UMR1213 Herbivores, F-63112 Saint-Genès-Champanelle, France.|Université de Lyon - VetAgro Sup, UMR1213 Herbivores, F-69280 Marcy l'Etoile, France.
authors.forename: Denys
authors.initials: D
authors.lastname: Durand
authors.affiliation: INRA, UMR1019, Plateforme d'Exploration du Métabolisme, F-63000 Clermont-Ferrand, France and.|INRA, UMR1019, UNH, F-63000 Clermont-Ferrand, France.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Joly
authors.affiliation: INRA, UMR1019, Plateforme d'Exploration du Métabolisme, F-63000 Clermont-Ferrand, France and.|INRA, UMR1019, UNH, F-63000 Clermont-Ferrand, France.
authors.forename: Estelle
authors.initials: E
authors.lastname: Pujos-Guillot
authors.affiliation: Toxalim, Université de Toulouse, INRA, INP-ENVT, INP-EI-Purpan, Université de Toulouse 3 Paul Sabatier, 180 chemin de Tournefeuille, F-31027 Toulouse, France.|Université de Toulouse III, INP, ENVT, UPS, TOXALIM, F-31027 Toulouse, France.
authors.forename: Fabrice H
authors.initials: FH
authors.lastname: Pierre
authors.affiliation: Toxalim, Université de Toulouse, INRA, INP-ENVT, INP-EI-Purpan, Université de Toulouse 3 Paul Sabatier, 180 chemin de Tournefeuille, F-31027 Toulouse, France.|Université de Toulouse III, INP, ENVT, UPS, TOXALIM, F-31027 Toulouse, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Huc
mesh_terms: D000447:Aldehydes; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D017209:Apoptosis; D003106:Colon / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000209:etiology*; D005243:Feces; D006454:Hemoglobins / Q000494:pharmacology*; D008658:Inactivation, Metabolic; D008297:Male; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D011230:Precancerous Conditions / Q000378:metabolism / Q000473:pathology; D011916:Rats, Inbred F344; D000069466:Red Meat / Q000009:adverse effects*
chemical_list: D000447:Aldehydes; D000975:Antioxidants; D006454:Hemoglobins; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; C027576:4-hydroxy-2-nonenal