Since epidemiological studies have firmly implicated co-exposure to
iron oxides and
polycyclic aromatic hydrocarbons as a potential etiological factor involved in the excess mortality due to
lung cancer in miners, experimental studies have been performed to investigate the role of
iron particles in
benzo[a]pyrene (B[a]P)-induced lung pathogenesis. In a previous study using the Comet assay in vivo in the rat, we demonstrated that
iron particles enhanced B[a]P genotoxicity. To determine whether co-exposure (B[a]P/
iron oxides) induces a real genotoxic activity or is only due to inhibition of DNA repair, the unscheduled
DNA synthesis (UDS) assay was implemented in vivo in the rat. The UDS assay was used to measure DNA repair in two cell types (lung cells and hepatocytes) of OFA Sprague-Dawley rats, 24 h after endotracheal administration of a single dose of an
iron oxide (
hematite, Fe2O3) (0.75 mg), of B[a]P (0.75 mg) or of B[a]P (0.75 mg) coated on
hematite particles (0.75 mg). No difference in UDS was observed in the two organs investigated in rats treated with
iron oxide alone compared with control animals, while a significant increase in UDS was observed in lungs and liver of rats treated with B[a]P alone compared with control animals. The main finding was a significant increase in UDS observed in both lung and liver cells of rats treated with B[a]P coated on
hematite when compared with those treated with B[a]P alone. The current study demonstrates (i) that
iron particles did not inhibit UDS in lung cells and hepatocytes of OFA Sprague-Dawley treated rats with B[a]P coated on
hematite and (ii) a potent genotoxic activity of co-exposure to B[a]P coated on
hematite. Therefore, our data may contribute to explaining the excess mortality due to
lung cancer in epidemiological studies and overall why exposure to B[a]P coated on Fe2O3 particles resulted in a higher
tumor incidence in rodents compared with exposure to B[a]P alone.