DNA damage in lung after oral exposure to diesel exhaust particles in Big Blue (R) rats

Anne Kirstine Müller, E.O. Farombi, P. Møller, H.N. Autrup, U. Vogel, H. Wallin, Lars Ove Dragsted, S. Loft, Mona-Lise Binderup

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Several chemical mutagens and carcinogens, including polycyclic aromatic hydrocarbons (PAHs) and nitrated PAHs, are adsorbed to the surface of diesel exhaust particles (DEP). DEP can induce formation of reactive oxygen species and cause oxidative DNA damage as well as bulky carcinogen DNA adducts. Lung tissue is a target organ for DEP induced cancer following inhalation. Recent studies have provided evidence that the lung is also a target organ for DNA damage and cancer after oral exposure to other complex mixtures of PAHs. The genotoxic effect of oral administration of DEP was investigated, in terms of markers of DNA damage, mutations and repair, in the lung of Big Blue(R) rats fed a diet with 0, 0.2, 0.8, 2, 8, 20 or 80 mg DEP/kg feed for 21 days. There was no significant increase in the mutation frequency in the cII gene. However, an increase of DNA damage measured as DNA strand breaks (comet assay) and bulky DNA adducts (P-32 post labeling) was observed. The level of DNA strand breaks increased significantly at all dose levels while the level of DNA adducts increased significantly only at the intermediate dose levels. Similarly, the number of oxidized DNA bases measured as endonuclease III and fapyguanine glycosylase (FPG) sensitive sites increased at the intermediate dose levels. The induction of DNA damage by DEP exposure did not increase the expression of the repair genes OGG1 and ERCC1 at the mRNA level. The present study indicates that the lung is a target organ for primary DNA damage following oral exposure to DEP. DNA damage was induced following exposure to relatively low levels of DEP, but under the conditions used in the present experiment DNA damage did not result in an increased mutation rate.
Original languageEnglish
JournalMutation research
Volume550
Issue number1-2
Pages (from-to)123-132
ISSN0027-5107
Publication statusPublished - 2004

Keywords

  • DNA strand breaks
  • mutations
  • OGGI
  • ERCCI
  • oxidative DNA damage
  • diesel exhaust
  • Big Blue((R)) rats
  • bulky DNA adducts

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