title: DNA adduct formation and oxidative stress in colon and liver of Big Blue rats after dietary exposure to diesel particles.
abstract: Exposure to diesel exhaust particles (DEP) via the gastrointestinal route may impose risk of cancer in the colon and liver. We investigated the effects of DEP given in the diet to Big Blue rats by quantifying a panel of markers of DNA damage and repair, mutation, oxidative damage to proteins and lipids, and antioxidative defence mechanisms in colon mucosa cells, liver tissue and the blood compartment. Seven groups of rats were fed a diet with 0, 0.2, 0.8, 2, 8, 20 or 80 mg DEP/kg feed for 21 days. DEP induced a significant increase in DNA strand breaks in colon and liver. There was no effect on oxidative DNA damage (8-oxodG) in colon or liver DNA or in the urine. However, the mRNA expression of OGG1, encoding an enzyme involved in repair of 8-oxodG, was increased by DEP in both liver and colon. DNA adduct levels measured by 32P-post-labelling were elevated in colon and liver, and the expression of ERCC1 gene was affected in liver, but not in colon. In addition to these effects, DEP exposure induced apoptosis in liver. There was no significant change in mutation frequency in colon or liver. The levels of oxidative protein modifications (oxidized arginine and proline residues) were increased in liver accompanied by enhanced vitamin C levels. In plasma, we found no significant effects on oxidative damage to proteins and lipids, antioxidant enzymes or vitamin C levels. Our data indicate that gastrointestinal exposure to DEP induces DNA adducts and oxidative stress resulting in DNA strand breaks, enhanced repair capacity of oxidative base damage, apoptosis and protein oxidation in colon mucosa cells and liver.
authors.affiliation: Department of Chemical Work Environment, National Institute of Occupational Health, Copenhagen, Denmark. md@ami.dk
authors.forename: Marianne
authors.initials: M
authors.lastname: Dybdahl
authors.forename: Lotte
authors.initials: L
authors.lastname: Risom
authors.forename: Peter
authors.initials: P
authors.lastname: Møller
authors.forename: Herman
authors.initials: H
authors.lastname: Autrup
authors.forename: Håkan
authors.initials: H
authors.lastname: Wallin
authors.forename: Ulla
authors.initials: U
authors.lastname: Vogel
authors.forename: Jette
authors.initials: J
authors.lastname: Bornholdt
authors.forename: Bahram
authors.initials: B
authors.lastname: Daneshvar
authors.forename: Lars Ove
authors.initials: LO
authors.lastname: Dragsted
authors.forename: Allan
authors.initials: A
authors.lastname: Weimann
authors.forename: Henrik Enghusen
authors.initials: HE
authors.lastname: Poulsen
authors.forename: Steffen
authors.initials: S
authors.lastname: Loft
mesh_terms: D000818:Animals; D001483:Base Sequence; D001835:Body Weight; D003106:Colon / Q000378:metabolism*; D018736:DNA Adducts / Q000096:biosynthesis*; D004249:DNA Damage; D045647:DNA Glycosylases / Q000235:genetics; D017931:DNA Primers; D004260:DNA Repair; D004268:DNA-Binding Proteins; D004032:Diet; D004305:Dose-Response Relationship, Drug; D004720:Endonucleases; D020287:In Situ Nick-End Labeling; D008099:Liver / Q000378:metabolism*; D009929:Organ Size; D018384:Oxidative Stress; D011506:Proteins / Q000235:genetics; D051381:Rats; D001335:Vehicle Emissions
chemical_list: D018736:DNA Adducts; D017931:DNA Primers; D004268:DNA-Binding Proteins; D011506:Proteins; D001335:Vehicle Emissions; D004720:Endonucleases; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human