MORPHOLOGICAL-CHANGES AND PROLIFERATIVE ACTIVITY OF ALVEOLAR EPITHELIUM IN MOUSE LUNGS TREATED WITH URETHANE

We have observed sequential cellular changes in type II pneumocytes in mouse lungs following oral administration of 0.1% urethan solution. H istologically, scatterings of swollen alveolar cells were first notice d 25 days after administration. These cells continued to swell further , after which they aggregated more compactly to form a papillary struc ture by day 75. After day 100, distinct tumour nodules were found with atypical large cells in some areas. Necrotic foci appeared in large t umours of more than 4 mm diameter. At day 250, nucleoli became distinc t and large bizarre and multinucleated cells were intermingled with so me mitotic figures. These morphologies correspond to conventional desc riptions; that is, hyperplasia (day 25-75), benign neoplastic changes (day 75-100) and malignant neoplastic changes (day 100-250). The proli ferating cell nuclear antigen (PCNA) and nucleolar organizer regions ( AgNOR) scores in these lesions increased with time, and proliferative activities during tumour progression seemed continuous. However, proli ferative activity of the cells on specific days did not differ statist ically from the values on neighboring days. We speculate that the hype rplasia-like lesions seen in our mice are neoplastic in nature from th eir outset.