title: Effect of increased intake of dietary animal fat and fat energy on oxidative damage, mutation frequency, DNA adduct level and DNA repair in rat colon and liver.
abstract: The effect of high dietary intake of animal fat and an increased fat energy intake on colon and liver genotoxicity and on markers of oxidative damage and antioxidative defence in colon, liver and plasma was investigated in Big Blue rats. The rats were fed ad libitum with semi-synthetic feed supplemented with 0, 3, 10 or 30% w/w lard. After 3 weeks, the mutation frequency, DNA repair gene expression, DNA damage and oxidative markers were determined in liver, colon and plasma. The mutation frequency of the lambda gene cII did not increase with increased fat or energy intake in colon or liver. The DNA-adduct level measured by 32P-postlabelling decreased in both liver and colon with increased fat intake. In liver, this was accompanied by a 2-fold increase of the mRNA level of nucleotide excision repair (NER) gene ERCC1. In colon, a non-statistically significant increase in the ERCC1 mRNA levels was observed. Intake of lard fat resulted in increased ascorbate synthesis and affected markers of oxidative damage to proteins in liver cytosol, but not in plasma. The effect was observed at all lard doses and was not dose-dependent. However, no evidence of increased oxidative DNA damage was found in liver, colon, or urine. Thus, lard intake at the expense of other nutrients and a large increase in the fat energy consumption affects the redox state locally in the liver cytosol, but does not induce DNA-damage, systemic oxidative stress or a dose-dependent increase in mutation frequency in rat colon or liver.
authors.affiliation: National Institute of Occupational Health, Lersø Parkallé 105, DK-2100, Copenhagen, Denmark. ubv@ami.dk
authors.forename: Ulla
authors.initials: U
authors.lastname: Vogel
authors.forename: Bahram
authors.initials: B
authors.lastname: Danesvar
authors.forename: Herman
authors.initials: H
authors.lastname: Autrup
authors.forename: Lotte
authors.initials: L
authors.lastname: Risom
authors.forename: Allan
authors.initials: A
authors.lastname: Weimann
authors.forename: Henrik Enghusen
authors.initials: HE
authors.lastname: Poulsen
authors.forename: Peter
authors.initials: P
authors.lastname: Møller
authors.forename: Steffen
authors.initials: S
authors.lastname: Loft
authors.forename: Håkan
authors.initials: H
authors.lastname: Wallin
authors.forename: Lars O
authors.initials: LO
authors.lastname: Dragsted
mesh_terms: D000818:Animals; D003106:Colon / Q000378:metabolism*; D018736:DNA Adducts; D004249:DNA Damage; D045647:DNA Glycosylases / Q000235:genetics; D004260:DNA Repair / Q000502:physiology*; D004268:DNA-Binding Proteins; D004041:Dietary Fats / Q000378:metabolism*; D004720:Endonucleases; D002149:Energy Intake; D008099:Liver / Q000378:metabolism*; D008297:Male; D009154:Mutation; D018384:Oxidative Stress / Q000502:physiology*; D011506:Proteins / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D018736:DNA Adducts; D004268:DNA-Binding Proteins; D004041:Dietary Fats; D011506:Proteins; D004720:Endonucleases; D045647:DNA Glycosylases; C483741:OGG1 protein, rat