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 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 (32P 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.