Influence of exposure regimen on nitrogen dioxide-induced morphological changes in the rat lung.
Experiments were performed to study the influence of concentration, exposure pattern, and length of exposure on the degree and extent of morphological alterations in the NO2-exposed rat lung. Four weeks of continuous exposure to 20 mg NO2/m3 consecutively revealed damage and loss of cilia, replacement of desquamated type I pneumocytes by type II pneumocytes resulting in a cuboidal epithelial lining, an influx of alveolar macrophages, and hypertrophy and hyperplasia of the bronchiolar epithelium. The animals recovered almost completely from the induced lesions within 8 days. Continuous exposure to 1, 2.5, or 5 mg/m3 displayed minimal alterations in the 5 mg/m3 group. The effects increased with exposure time. Intermittent or continuous exposure to 20 mg NO2/m3 resulted in minor differences after 4 weeks. The onset of the lesions was delayed and the massive influx of alveolar macrophages in the continuously exposed animals failed to appear in the intermittently exposed animals. This work demonstrates that in subacute experiments: Concentration plays a more important role in inducing pulmonary lesions than exposure time when the product of concentration and time is kept constant. This effect is stronger during intermittent exposure than during continuous exposure. Continuous exposure seems to be a more important factor with regard to a macrophage response than intermittent exposure. The rat lung has a large capacity to repair almost completely from damage caused by short-term NO2 exposure.
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006965:Hyperplasia; D008168:Lung / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D008264:Macrophages / Q000473:pathology; D008297:Male; D008855:Microscopy, Electron, Scanning; D009585:Nitrogen Dioxide / Q000008:administration & dosage / Q000633:toxicity*; D011656:Pulmonary Emphysema / Q000139:chemically induced; D051381:Rats; D011919:Rats, Inbred Strains
D009585:Nitrogen Dioxide