title: Long-term exposure to ozone increases acute pulmonary centriacinar injury by 1-nitronaphthalene: II. Quantitative histopathology.
abstract: Long-term exposure to the oxidant air pollutant ozone (O(3)) is associated with tolerance to the acute effects of oxidant injury. To test whether this resistance to acute injury extends to bioactivated pulmonary toxicants, male Sprague-Dawley rats were exposed to filtered air (FA) or 0.8 ppm O(3) (8 h/day) for 90 days and administered 1-nitronaphthalene i.p. at doses of 0, 50, or 100 mg/kg. 1-Nitronaphthalene is a pulmonary cytotoxicant requiring metabolic activation. High-resolution histopathology, transmission electron microscopy, and morphometry revealed significantly greater 1-nitronaphthalene toxicity in the central acinar region of O(3)- compared with FA-exposed rats. At 100 mg/kg, injury to terminal bronchioles in O(3)-exposed rats involved denudation of 86% of the basement membrane; 78% of the cells remaining on the epithelium were necrotic. This is compared with denudation of 4% of the basement membrane of FA-exposed rats administered 100 mg/kg 1-nitronaphthalene; only 25% of the cells remaining on the epithelium were necrotic. The key difference between FA- and O(3)-exposed rats treated with 1-nitronaphthalene was the heightened severity of ciliated cell toxicity in O(3)-exposed animals. This is despite the fact that long-term exposure to ozone produces tolerance to oxidant stress in the epithelium of the central acinus. No differences in the susceptibility of intrapulmonary airways or trachea to 1-nitronaphthalene were observed between filtered air- and ozone-exposed rats. This study demonstrates a site-selective synergy between the copollutants ozone and 1-nitronaphthalene in the production of acute lung injury.
authors.affiliation: Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California, Davis, California 95616, USA. rcpaige@ucdavis.edu
authors.forename: R C
authors.initials: RC
authors.lastname: Paige
authors.forename: V
authors.initials: V
authors.lastname: Wong
authors.forename: C G
authors.initials: CG
authors.lastname: Plopper
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D008168:Lung / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D009281:Naphthalenes / Q000633:toxicity*; D010126:Ozone / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000393:Air Pollutants; D009281:Naphthalenes; D010126:Ozone; C016614:1-nitronaphthalene