An ultrastructural study of the acute effects of 4-nitroquinoline 1-oxide on the hamster lung

The alterations, visible by light and electron microscopy, in the distal airway cells of Syrian golden hamsters were analyzed at several time intervals, from 6 hr to 4 weeks, after a single subcutaneous injection (120 mg/kg body wt) of 4-nitroquinoline 1-oxide (4NQO), a potent carcinogen. 4NQO induced injurious effects selectively on the bronchiolo-alveolar region, and morphological changes were recognizable within 12 hr after the injection. Both ciliated and nonciliated (Clara) cells of the bronchiole revealed degeneration, especially marked proliferation and dilation of smooth endoplasmic reticulum of the latter cell. Alveolar epithelial and endothelial cells were damaged, showing diffuse exudative inflammation. These regressive changes were most prominent on the third day of the experiment. After the fourth day, large cuboidal cells with scanty organelles in their abundant cytoplasm proliferated along the alveolar surfaces in the process of repairing the damaged lung tissue, and then tubular structures in the alveoli were formed. Mitotic activity appeared in the epithelium around the bronchiolo-alveolar junctional area, and immature cells with a few organelles were formed. After 2 weeks, the inflammatory changes and cell renewal in the alveoli disappeared, and bronchiolization was established as a result of atypical maturation of the respiratory cells just around the bronchiolo-alveolar junctional area.