Abstract
Long-term exposure to the oxidant air pollutant ozone (O3) 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 O3 (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 O3- compared with FA-exposed rats. At 100 mg/kg, injury to terminal bronchioles in O3-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 O3-exposed rats treated with 1-nitronaphthalene was the heightened severity of ciliated cell toxicity in O3-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.
Footnotes
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Send reprint requests to: Dr. Renee Paige, Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California, Davis, Davis, CA 95616. E-mail:rcpaige{at}ucdavis.edu
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↵1 This work is funded by National Institute on Environmental Health Sciences ES00628, ES09681, ES04311, and T32 ES07059. UC Davis is a National Institute on Environmental Health Sciences Center (ES05707) and support for core facilities used in this work is gratefully acknowledged.
- Abbreviation:
- 1-NN
- 1-nitronaphthalene
- Received May 23, 2000.
- Accepted August 15, 2000.
- The American Society for Pharmacology and Experimental Therapeutics
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