Hematite (Fe(2)O(3)) enhances benzo[a]pyrene genotoxicity in endotracheally treated rat, as determined by Comet Assay.
Since epidemiological studies have firmly implied the co-exposition between iron oxides and polycyclic aromatic hydrocarbons (PAH) as potential etiological factor involved in the excess of mortality by lung cancer in miners, experimental studies have been performed to investigate the role of iron particles on benzo[a]pyrene (B[a]P)-induced lung pathogenesis. In the present study, the alkaline single-cell gel electrophoresis (SCGE; Comet Assay) was used to measure DNA single-strand breaks in four cell types (alveolar macrophages, lung cells, peripheral lymphocytes and hepatocytes) of OFA Sprague-Dawley rats 24h after endotracheal administration of a single dose of an iron oxide (hematite; Fe(2)O(3)) (0.75mg) or B[a]P (0.75mg) or B[a]P (0.75mg) coated onto hematite particles (0.75mg). No damage was observed in cell from the four investigated organs in rats treated with iron oxide alone, while a statistically significant increase in DNA damage was observed compared with control animals in all tested cell types of rats treated with B[a]P alone or in association with hematite. The highest levels of damage were observed in lung cells and peripheral lymphocytes; the levels of damage in alveolar macrophages and hepatocytes were increased, but to a lesser extent compared with the first two cell types. The main finding was to notice a statistically significant increase of the damage in all organs of rats treated with B[a]P coated onto hematite (approximately two-fold increases; P<0.001), versus B[a]P alone. The current study shows that iron particles increase the genotoxic properties of B[a]P in the respiratory tract of endotracheally treated OFA Sprague-Dawley rats. Hence, our data may contribute to explain the excess mortality by lung cancer in epidemiological studies and overall why exposures to B[a]P coated onto Fe(2)O(3) particles resulted in higher toxicity in rodents compared with exposure to B[a]P alone.
Garry
Sébastien
S
Laboratoire de Toxicologie Génétique, Institut Pasteur de Lille, France.
Nesslany
Fabrice
F
Aliouat
ElMoukhtar
E
Haguenoer
Jean-Marie
JM
Marzin
Daniel
D
D000818:Animals; D001564:Benzo(a)pyrene / Q000008:administration & dosage / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay; D004249:DNA Damage; D004357:Drug Synergism; D005290:Ferric Compounds / Q000008:administration & dosage / Q000633:toxicity*; D022781:Hepatocytes / Q000187:drug effects; D007442:Intubation, Intratracheal; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008168:Lung / Q000187:drug effects / Q000473:pathology; D016676:Macrophages, Alveolar / Q000187:drug effects; D008297:Male; D016296:Mutagenesis; D009153:Mutagens / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
D005290:Ferric Compounds; D009153:Mutagens; C000499:ferric oxide; D001564:Benzo(a)pyrene