Naturally occurring and N-
nitrosomethylurea-induced lung
tumors were studied in male F344/NCr rats by sequential histological, electron microscopic, and immunohistochemical methods. Rats were given one injection at 6 weeks of age of N-
nitrosomethylurea at a dosage level of 41.2 mg/kg
body weight i.v. Groups of rats were sacrificed at 20, 33, and 52 weeks, while some were sacrificed while moribund. Nine lung
tumors from aged F344/NCr male rats were also studied. For determining localization of pulmonary
antigens, sections of lungs were stained by the
avidin-
biotin-
peroxidase complex immunocytochemical technique using
antibodies to rat
surfactant apoprotein or rat
Clara cell antigen. At 20 weeks, in rats receiving N-
nitrosomethylurea, focal alveolar type II cell
hyperplasia,
adenoma in focal alveolar type II cell
hyperplasia, and
adenoma were found in 15 (100%), 1 (7%), and 2 (13%) of 15 rats, respectively. At 33 weeks, there were 19 rats (95%) with focal alveolar type II cell
hyperplasias, 10 rats (50%) with
adenoma in focal alveolar type II cell
hyperplasia, and 2 rats (10%) with
adenomas in 20 rats. In 53 rats allowed to live up to 52 weeks, there were 10 (19%)
adenomas and 3 (6%)
carcinomas, as well as 49 (92%) rats with focal
hyperplasia and 31 (58%) with
adenomas in focal type II cell
hyperplasia. Rat
surfactant apoprotein was found in the cytoplasm of normal alveolar type II cells and the majority of cells in focal alveolar type II cell
hyperplasias,
adenomas in hyperplastic lesions,
adenomas, and
carcinomas. The ultrastructure of these lesions supported immunocytochemical findings with evidence of lamellar bodies. All nine naturally occurring lung
tumors studied contained rat
surfactant apoprotein. Rat
Clara cell antigen was found, however, only focally within one
adenoma induced by N-
nitrosomethylurea and one
adenoma in a hyperplastic lesion, and also focally in three
neoplasms which occurred naturally. This study provided morphological, immunohistochemical, and ultrastructural evidence that the vast majority of N-
nitrosomethylurea-induced and naturally occurring
pulmonary neoplasms of F344 rats are alveolar type II cell
adenomas and
carcinomas and that a portion of these
tumors arise within focal alveolar type II cell
hyperplasias.