Clara cell adenomas of the mouse lung. Interaction with alveolar type 2 cells.
Multiple pulmonary adenomas were induced in the offspring of pregnant Swiss-Webster mice by transplacental exposure to ethylnitrosourea (ENU) on the 15th day of gestation. Development and growth of tumors were followed for up to a year after birth. Morphologic assessment indicated that the majority of adenomas were of Clara-cell origin and were relatively normal on the basis of structural features. Histochemical studies, utilizing nitroblue tetrazolium reductase activity as a marker for normal Clara cells demonstrated that the Clara-cell-derived tumors possessed nearly normal enzyme activity. Microscopic studies of the tumors and adjacent parenchyma revealed a unique Type 2 cell response to the presence of Clara-cell adenomas occurring in the alveoli beyond the margins of the tumor. Otherwise normal-appearing Type 2 cells, in a narrow zone around the Clara-cell tumors, accumulated large amounts of surfactantlike osmiophilic lamellar material within cytoplasmic vacuoles as early as 30 days after birth. These changes were clearly a Clara-cell-tumor-related response, and not seen in association with other non-Clara-cell adenomas of the same lung. Furthermore, the alterations occurred exclusively in Type 2 cells. The extent of Type 2 cell change was correlated with tumor size and age. Autoradiographic studies with tritiated choline showed marked incorporation of the labeled precursor by the altered Type 2 cells. By electron microscopy, these inclusions were membrane-limited and contained osmiophilic lamellar structures similar to lamellar bodies in normal Type 2 cells. Because these Clara cell adenomas may act as a concentrated focus of normal Clara cells, the alterations seen in Type 2 cells may reflect an amplification of a normal interaction between bronchiolar Clara cells and alveolar Type 2 cells in the centriacinar and juxtabronchiolar alveoli.
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D000236:Adenoma / Q000139:chemically induced / Q000473:pathology*; D000367:Age Factors; D000818:Animals; D001345:Autoradiography; D001980:Bronchi / Q000473:pathology / Q000648:ultrastructure; D003594:Cytoplasmic Granules / Q000648:ultrastructure; D005038:Ethylnitrosourea; D005260:Female; D006651:Histocytochemistry; D002479:Inclusion Bodies / Q000648:ultrastructure; D008175:Lung Neoplasms / Q000139:chemically induced / Q000473:pathology*; D051379:Mice; D008854:Microscopy, Electron; D011247:Pregnancy; D011650:Pulmonary Alveoli / Q000473:pathology* / Q000648:ultrastructure; D013194:Staining and Labeling
D005038:Ethylnitrosourea