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Title: Long-term ozone exposure attenuates 1-nitronaphthalene-induced cytotoxicity in nasal mucosa.

Authors: Lee, Myong Gyong; Wheelock, Asa M; Boland, Bridget; Plopper, Charles G

Published In Am J Respir Cell Mol Biol, (2008 Mar)

Abstract: 1-Nitronaphthalene (1-NN) and ozone are cytotoxic air pollutants commonly found as components of photochemical smog. The mechanism of toxicity for 1-NN involves bioactivation by cytochrome P450s and subsequent adduction to proteins. Previous studies have shown that 1-NN toxicity in the lung is considerably higher in rats after long-term exposure to ozone compared with the corresponding filtered air-exposed control rats. The aim of the present study was to establish whether long-term exposure to ozone alters the susceptibility of nasal mucosa to the bioactivated toxicant, 1-NN. Adult male Sprague-Dawley rats were exposed to filtered air or 0.8 ppm ozone for 8 hours per day for 90 days, followed by a single treatment with 0, 12.5, or 50.0 mg/kg 1-NN by intraperitoneal injection. The results of the histopathologic analyses show that the nasal mucosa of rats is a target of systemic 1-NN, and that long-term ozone exposure markedly lessens the severity of injury, as well as the protein adduct formation by reactive 1-NN metabolites. The antagonistic effects were primarily seen in the nasal transitional epithelium, which corresponds to the main site of histologic changes attributed to ozone exposure (goblet cell metaplasia and hyperplasia). Long-term ozone exposure did not appear to alter susceptibility to 1-NN injury in other nasal regions. This study shows that long-term ozone exposure has a protective effect on the susceptibility of nasal transitional epithelium to subsequent 1-NN, a result that clearly contrasts with the synergistic toxicological effect observed in pulmonary airway epithelium in response to the same exposure regimen.

PubMed ID: 17901409 Exiting the NIEHS site

MeSH Terms: Air Pollutants/toxicity*; Alcian Blue/metabolism; Animals; Dose-Response Relationship, Drug; Histocytochemistry; Hydrogen-Ion Concentration; Injections, Intraperitoneal; Male; Models, Biological; Naphthalenes/administration & dosage; Naphthalenes/toxicity*; Nasal Mucosa/metabolism; Nasal Mucosa/pathology*; Olfactory Mucosa/metabolism; Olfactory Mucosa/pathology; Ozone/toxicity*; Periodic Acid-Schiff Reaction; Rats; Rats, Sprague-Dawley; Toxicity Tests, Chronic

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