Journal Article

Development of Pulmonary Tolerance in Mice Exposed to Zinc Oxide Fumes

Scott C. Wesselkamper, Lung Chi Chen and Terry Gordon

in Toxicological Sciences

Volume 60, issue 1, pages 144-151
Published in print March 2001 | ISSN: 1096-6080
Published online March 2001 | e-ISSN: 1096-0929 | DOI: http://dx.doi.org/10.1093/toxsci/60.1.144
Development of Pulmonary Tolerance in Mice Exposed to Zinc Oxide Fumes

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As a result of repeated exposures to inhaled toxicants such as zinc oxide (ZnO), numerous individuals acquire tolerance to the exposures and display reduced symptoms. To ascertain whether tolerance is developed in an animal model, NIH-Swiss mice were exposed to 1.0 mg/m3 ZnO for 1, 3, or 5 days (1X, 3X, or 5X), and polymorphonuclear leukocyte (PMN) and protein levels in bronchoalveolar lavage (BAL) were measured. Mice acquired tolerance to neutrophil infiltration into the lungs, as total PMNs returned near baseline in 5X-exposed animals as compared to that of the 1X exposure group (1X = 2.7 ± 0.4 × 104, 5X = 0.2 ± 0.1 × 104, mean ± SE, p < 0.05). Development of tolerance to changes in lavageable protein, however, was not observed (1X = 313 ± 29 μg/ml, 5X = 684 ± 71μg/ml, p < 0.05). Tolerance to PMN influx did not persist following re-exposure to ZnO after 5 days of rest. In contrast to ZnO exposure, following single and repeated exposure to aerosolized endotoxin there was development of tolerance to protein in BAL (1X = 174 ± 71 μg/ml, 5X = 166 ± 14 μg/ml, p > 0.05), but not to PMN influx (1X = 5.5 ± 1.7× 104, 13.9 ± 1.7 × 104, p < 0.05). Induction of lung metallothionein (MT) was also observed in mice exposed once or repeatedly exposed to ZnO, suggesting that MT may play a role in its molecular mechanism.

Keywords: zinc oxide; tolerance; metallothionein; metal fume fever; endotoxin; adaptation

Journal Article.  6470 words.  Illustrated.

Subjects: Medical Toxicology ; Toxicology (Non-medical)

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