ULTRASTRUCTURE AND CELL PROLIFERATIVE ACTIVITIES OF KARYOMEGALIC ALVEOLAR EPITHELIAL-CELLS IN EARLY PULMONARY INFLAMMATORY LESIONS OF SYRIAN GOLDEN-HAMSTERS INDUCED BY N-METHYL-N-NITROSOURETHANE

To clarify the biological behavior of karyomegalic alveolar epithelial cells induced by N-methyl-N-nitrosourethane (MNUR) and whether these cells progress to lung tumors, female Syrian golden hamsters, 6 weeks old, were given five subcutaneous injections of 0.6 mg/animal of MNUR at two week intervals and their lungs were examined at weeks 1, 4, 8 a nd 12 after the termination of treatment. At week I, in severely affec ted areas where marked multifocal thickening of alveolar walls due to interstitial edema and cellular infiltration was observed, some regene rative alveolar epithelial cells had abundant eosinophilic cytoplasm a nd gigantic bizarre nuclei. The cells were confirmed ultrastructurally to be derived from alveolar type II cells. The number of these karyom egalic epithelial cells became significantly decreased thereafter, tog ether with the reduction of inflammatory changes. On AgNOR staining, n ormal alveolar epithelial cells had 1.8+/-0.03 black dots within their nuclei while the karyomegalic epithelial cells had 4 black dots or mo re, from I week. The PCNA labeling index of the karyomegalic epithelia l sells at week I was 14.6+/-2.4, and was significantly decreased from 4 week. This epithelial cell population also displayed a wider range of DNA contents (2.1-5.5C) than normal epithelial cells (1.6-2.3C). Th ese results suggest that karyomegalic alveolar epithelial cells may be mutant cells which occur after initiation with MNUR, but the possibil ity that they can act as progenitors of alveolar epithelial cell tumor s was considered to be extremely low.