Assessment of genotoxic effect of benzo[a]pyrene in endotracheally treated rat using the comet assay.
Although benzo[a]pyrene (B[a]P) is a well-known genotoxic agent, little is known about the extent of DNA effects induced by B[a]P in rat tissues after pulmonary exposure. The alkaline single-cell gel electrophoresis (comet assay) was used to measure DNA single-strand breaks in alveolar macrophages, lung cells, peripheral lymphocytes and hepatocytes of OFA Sprague-Dawley rats exposed to a single dose of B[a]P by endotracheal administration. Statistically significant damage was observed in all organs tested after 3, 24 and 48h of pulmonary exposure to 3mg of B[a]P per animal, with a time-dependent relationship. The maximum damage was observed in the four cell types 24h after exposure. The higher level of damage was observed both in lung cells and peripheral lymphocytes; in alveolar macrophages and hepatocytes the level of damage was increased, but at a lower level than in the two other cell types. Furthermore, B[a]P demonstrated a clear dose-related genotoxic activity in the lung cells when tested at doses of 0.75, 1.5 and 3mg. The current study shows that B[a]P caused DNA single-strand breaks in the respiratory tract of endotracheally treated OFA Sprague-Dawley rats. The study also suggests that pulmonary exposure to B[a]P can induce a high level of DNA damage in peripheral lymphocytes. The clear relationship between lung exposure to B[a]P and consequences observed in lymphocytes suggests that the comet assay in peripheral lymphocytes can be used as a sensitive marker in human monitoring studies.
Garry
Sébastien
S
Laboratoire de Toxicologie Génétique, Institut Pasteur de Lille, 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*; D020552:Comet Assay / Q000379:methods*; D004249:DNA Damage / Q000187:drug effects / Q000235:genetics; D004277:DNA, Single-Stranded / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D022781:Hepatocytes / Q000187:drug effects; D007442:Intubation, Intratracheal; D007700:Kinetics; D008168:Lung / Q000166:cytology / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects; D016676:Macrophages, Alveolar / Q000187:drug effects; D008297:Male; D009152:Mutagenicity Tests; D009153:Mutagens / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
D004277:DNA, Single-Stranded; D009153:Mutagens; D001564:Benzo(a)pyrene