Previously we have reported dose-related histological changes following administration of the metabolically activated pulmonary cytotoxicant 1-nitronaphthalene -(1-NN). In that study, slides were screened by high-resolution light microscopy on 0.5μm sections and graded by severity. Contrary to typical patterns of injury by metabolically activated xenobiotics, 1-NN injury appeared first in the minor daughter and not the terminal bronchiolar epithelium and involved both ciliated and nonciliated ("Clara") cells. To determine what ultrastractural changes were yielding necrosis of both ciliated and Clara cells, and to identify what, if any, ultrastructural changes may be present in cells appearing normal by high-resolution light microscopy, we reevaluated the original samples by transmission electron microscopy (TEM). Injury, not detectable by light microscopy, observed by TEM in Clara cells of rats administered low doses of 1-NN (25 and 50 mg/kg) included marked degeneration of mitochondria, swelling of the endoplasmic reticulum (ER) and chromatin condensation. Early degenerative changes observed in ciliated cells included swelling of perinuclear ER and increased opacity of the mitochondrial matrix. Active ciliogenesis was also observed at 50 mg/kg. These observations underscore the need for assessing acute toxicity by a variety of methods, including those of high resolution.
|Original language||English (US)|
|State||Published - Mar 20 1998|
ASJC Scopus subject areas
- Molecular Biology