title: Dietary elevated sucrose modulation of diesel-induced genotoxicity in the colon and liver of Big Blue rats.
abstract: Earlier studies have indicated that sucrose possesses either co-carcinogenic or tumor-promoter effects in colon carcinogenesis induced by genotoxic carcinogens. In this study we investigated the role of sucrose on diesel exhaust particle (DEP)-induced genotoxicity in the colonic mucosa and liver. Big Blue rats were fed with DEP (0.8 ppm in feed) and/or sucrose (3.45% or 6.85% w/w in feed) for 3 weeks. DEP increased both DNA strand breaks and DNA adducts in colon. Interestingly, sucrose also increased the level of bulky DNA adducts in colon. DEP and sucrose had no effect on DNA strand-breaks and DNA adducts in liver. DEP and sucrose treatment did not have any effect on mutation frequency in colon and liver. Oxidative DNA damage detected as 8-oxodG (8-oxo-7,8-dihydro-2'-deoxyguanosine) and endonuclease III or formamidopyrimidine DNA glycosylase sensitive sites was unaltered in colon and liver. The mRNA expression levels of the DNA repair enzymes N-methylpurine DNA glycosylase ( MPG), 8-oxoguanine DNA glycosylase ( OGG1) and ERCC1 (part of the nucleotide excision repair complex) measured by reverse transcription-polymerase chain reaction were increased in liver by DEP feeding. In colon, expression was unaffected by DEP or sucrose feeding. Among biomarkers of oxidative stress, including vitamin C, malondialdehyde and protein oxidations (gamma-glutamyl semialdehyde and 2-amino adipic semialdehyde) in plasma and liver, only malondialdehyde was increased in plasma by sucrose/DEP feeding. In conclusion, sucrose feeding did not increase DEP-induced DNA damage in colon or liver.
authors.affiliation: Institute of Public Health (c/o Department of Pharmacology), University of Copenhagen, Blegdamsvej 3, 2200, Copenhagen, Denmark.
authors.forename: Lotte
authors.initials: L
authors.lastname: Risom
authors.forename: Peter
authors.initials: P
authors.lastname: Møller
authors.forename: Max
authors.initials: M
authors.lastname: Hansen
authors.forename: Herman
authors.initials: H
authors.lastname: Autrup
authors.forename: Jette
authors.initials: J
authors.lastname: Bornholdt
authors.forename: Ulla
authors.initials: U
authors.lastname: Vogel
authors.forename: Håkan
authors.initials: H
authors.lastname: Wallin
authors.forename: Henrik E
authors.initials: HE
authors.lastname: Poulsen
authors.forename: Lars O
authors.initials: LO
authors.lastname: Dragsted
authors.forename: Steffen
authors.initials: S
authors.lastname: Loft
mesh_terms: D000818:Animals; D001345:Autoradiography; D002855:Chromatography, Thin Layer; D003106:Colon / Q000473:pathology*; D004249:DNA Damage; D045647:DNA Glycosylases / Q000187:drug effects / Q000235:genetics; D004260:DNA Repair / Q000187:drug effects / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D019422:Dietary Sucrose / Q000633:toxicity*; D004720:Endonucleases / Q000378:metabolism; D008099:Liver / Q000473:pathology*; D008297:Male; D009153:Mutagens / Q000633:toxicity*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D004268:DNA-Binding Proteins; D019422:Dietary Sucrose; D009153:Mutagens; D012333:RNA, Messenger; D001335:Vehicle Emissions; D004720:Endonucleases; D045647:DNA Glycosylases; C483741:OGG1 protein, rat