Cells of Origin of Primary Pulmonary Neoplasms in Mice: Morphologic and Histochemical Studies

Urethane-induced pulmonary adenomas in mice have two distinct histologic growth patterns--solid and papillary. The development of these tumors between 14 and 56 weeks was investigated in A/J mice. Solid tumor multiplicity remained constant from 14 to 56 weeks, whereas papillary and total tumor multiplicities increased in parallel between 14 and 28 weeks and remained constant through 56 weeks. The simplest explanation of these results is that solid and papillary adenomas arise independently, possibly from different cell types. The cell type of origin of these primary mouse lung tumors was investigated histochemically. Succinate dehydrogenase (SDH) histochemistry readily stained bronchiolar epithelial cells, but alveolar epithelial cells exhibited only slight enzymatic activity. Urethane-induced papillary adenomas exhibited intense SDH staining, whereas solid adenomas stained very lightly. Since Clara cells and type II pneumocytes are the only cells capable of proliferation in the bronchiolar and alveolar epithelia, respectively, the relative SDH activities of these adenomas is consistent with a hypothesis that solid tumors arise from type II pneumocytes and papillary tumors arise from Clara cells.