Sucrose, glucose and fructose have similar genotoxicity in the rat colon and affect the metabolome. |
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Authors: | M. Hansen,D. Baunsgaard,H. Autrup,U.B. Vogel,P. Mø ller,R. Lindecrona,H. Wallin,H.E. Poulsen,S. Loft,L.O. Dragsted |
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Affiliation: | 1. The National Food Institute, Technical University of Denmark, 19 Mørkhøj Bygade, DK-2860 Søborg, Denmark;2. Department of Protein Structure and Biophysics Novo Nordisk A/S, Novo Nordisk Park, DK-2760 Måløv, Denmark;3. Department of Environmental and Occupational Medicine, Vennelyst Boulevard 6, Building 260, Aarhus University, DK-8000 Aarhus C, Denmark;4. National Institute of Occupational Health, Lersø Parkallé 105, DK-2100 Copenhagen Ø, Denmark;5. Institute of Public Health, University of Copenhagen, Øster Farimagsgade 5A, 2-floor, 1014 Copenhagen K, Denmark;6. LEO Pharma A/S, Department of Preclinical Safety, Industriparken 55, DK-2750 Ballerup, Denmark;g Department of Clinical Pharmacology Q, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen Ø, Denmark;h Institute of Human Nutrition, University of Copenhagen, 30 Rolighedsvej DK-1958 Frederiksberg C, Denmark |
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Abstract: | We have shown previously that a high sucrose intake increases the background level of somatic mutations and the level of bulky DNA adducts in the colon epithelium of rats. The mechanism may involve either glucose or fructose formed by hydrolysis of sucrose. Male Big Blue rats were fed 30% sucrose, glucose, fructose or potato starch as part of the diet. Mutation rates and bulky DNA adduct levels were determined in colon and liver. The concentration of short-chain fatty acids and pH were determined in caecum, C-peptide was determined in plasma, biomarkers for oxidative damage and proliferation were determined in colon, and a metabonomic analysis was performed in plasma and urine. The sugars increased the mutation rates in colon and the bulky adduct levels in colon and liver to a similar extent. All sugars decrease the caecal concentration of acetic acid and propionic acid. The metabonomic studies indicated disturbed amino acid metabolism and decrease in plasma and urinary acetate as a common feature for all sugars and confirmed triglyceridemic effects of fructose. In conclusion, the genotoxicity may be related to the altered chemical environment in the caecum and thereby also in the colon but we found no related changes in insulin resistance or oxidative stress. |
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Keywords: | AAS, 2-amino adipic semialdehyde O-PLS-D, orthogonal projections to latent structures discriminant O-PLS-DA, orthogonal projections to latent structures discriminant analysis PCA, principal components analysis PCNA, proliferating cell nuclear antigen SCFA, short-chain fatty acid VLDL, very low density lipoprotein |
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