Effects of Acute no, Exposure in the Weanling Ferret Lung

Abstract

Because of its rapid growth from weanling to adult, and the similarity of the lung to primates, the ferret has been proposed as a model for use in inhalation toxicology The studies reported here were designed to evaluate this possibility. Weanling domestic ferrets (Mustela poturius furo) 6 wk of age were exposed nose-only for 4 h to atmospheres containing NO₂ at concentrations up to 20 ppm. At times up to 1 wk later, lungs were lavaged to recover free cells and the fixed lungs were examined by light microscopy for morphological changes. A dose-related influx of cells into the lung, mostly macrophages and neutrophils, was seen immediately post-exposure, and persisted up to 48 h. Cell recovery from the lung declined with time postexposure, reaching near control levels at 1 wk. A transient increase in eosino-phils was seen at 48 h postexposure. Protein content of the lung lavage fluid was not significantly different between NO₂-exposed and clean-air-exposed control animals. Morphometric measurements of lung parenchyma indicated dose-related decreased alveolar size and thickened alveolar walls at 48 h postexposure, suggestive of lung edema. Measurement of cellular proliferation by incorporation of [³H]thymidine and autoradiography showed a litter-specific, highly variable labeling index in the lung parenchyma, which obscured the analysis of any possible effects of the gas exposure on cell proliferation. This observation may be due to partial synchrony of cell division within litters. The conclusions were that the weanling ferret lung is sensitive to NO₂ over the same range of concentrations that affect other species, and that this animal model may be suited for studies of the effects of air pollutants on lung development.