title: Sucrose, glucose and fructose have similar genotoxicity in the rat colon and affect the metabolome.
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.
authors.affiliation: The National Food Institute, Technical University of Denmark, 19 Mørkhøj Bygade, DK-2860 Søborg, Denmark. mxh@dfvf.dk
authors.forename: M
authors.initials: M
authors.lastname: Hansen
authors.forename: D
authors.initials: D
authors.lastname: Baunsgaard
authors.forename: H
authors.initials: H
authors.lastname: Autrup
authors.forename: U B
authors.initials: UB
authors.lastname: Vogel
authors.forename: P
authors.initials: P
authors.lastname: Møller
authors.forename: R
authors.initials: R
authors.lastname: Lindecrona
authors.forename: H
authors.initials: H
authors.lastname: Wallin
authors.forename: H E
authors.initials: HE
authors.lastname: Poulsen
authors.forename: S
authors.initials: S
authors.lastname: Loft
authors.forename: L O
authors.initials: LO
authors.lastname: Dragsted
mesh_terms: D000818:Animals; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D004249:DNA Damage; D005632:Fructose / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009152:Mutagenicity Tests; D009154:Mutation / Q000187:drug effects*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D013395:Sucrose / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D013549:Sweetening Agents / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*
chemical_list: D013549:Sweetening Agents; D005632:Fructose; D013395:Sucrose; D005947:Glucose