Long-term ozone exposure attenuates 1-nitronaphthalene-induced cytotoxicity in nasal mucosa.
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.
Lee
Myong Gyong
MG
Lung Research Lab L4:01, Respiratory Medicine Unit, Department of Medicine, Karolinska Institutet, 171 76 Stockholm, Sweden. asa@para-docs.org
Wheelock
Asa M
AM
Boland
Bridget
B
Plopper
Charles G
CG
D000393:Air Pollutants / Q000633:toxicity*; D000423:Alcian Blue / Q000378:metabolism; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006651:Histocytochemistry; D006863:Hydrogen-Ion Concentration; D007274:Injections, Intraperitoneal; D008297:Male; D008954:Models, Biological; D009281:Naphthalenes / Q000008:administration & dosage / Q000633:toxicity*; D009297:Nasal Mucosa / Q000378:metabolism / Q000473:pathology*; D009831:Olfactory Mucosa / Q000378:metabolism / Q000473:pathology; D010126:Ozone / Q000633:toxicity*; D010503:Periodic Acid-Schiff Reaction; D051381:Rats; D017207:Rats, Sprague-Dawley; D036401:Toxicity Tests, Chronic
D000393:Air Pollutants; D009281:Naphthalenes; D010126:Ozone; C016614:1-nitronaphthalene; D000423:Alcian Blue