Abstract
To establish the characteristics of an optimized pulmonary fibrosis model, male ICR mice were given 4 weekly sc injections of 150 or 0 mg/kg monocrotaline (MCT) and maintained without further treatment for 33 wk (Experiment 1). The final mortality in the MCT group was 64%. Epithelial cells with large bizarre nuclei and an increased incidence of alveolar/bronchiolar hyperplasias were typically observed. In areas of pulmonary fibrosis, the PCNA labeling index (LI) in the alveolar/airway epithelium was significantly elevated. DNA content analysis demonstrated a larger range (4-8C) for the ploidy pattern of alveolar epithelium with large bizarre nuclei than in the normal epithelium (2C). In Experiment 2, the relationship between pulmonary fibrosis development and lung tumorigenesis was investigated. Mice were given 4 weekly sc injections of 150 and 0 mg/kg MCT, followed by a single i.p. injection of 1,000 or 500 mg/kg urethane (UR) on week 7, then maintained without further treatment for an additional 15 wk. UR following MCT-induced inflammatory changes, fibrosis, and epithelia with large bizarre nuclei but no tumorous lesions, in spite of the fact that treatment with UR alone caused a high incidence of pulmonary tumors. Hyperplasi...Continue Reading
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