PLUTONIUM-INDUCED PROLIFERATIVE LESIONS AND PULMONARY EPITHELIAL NEOPLASMS IN THE RAT - IMMUNOHISTOCHEMICAL AND ULTRASTRUCTURAL EVIDENCE FOR THEIR ORIGIN FROM TYPE-II PNEUMOCYTES

Immunohistochemistry and transmission electron microscopy were used to clarify the cellular origin for plutonium-239-induced pulmonary proli ferative (preneoplastic) epithelial lesions and epithelial neoplasms i n F344 rats. Examples of each histologic type of proliferative lesion and neoplasm were stained by the avidin-biotin complex immunoperoxidas e method using antibodies to rat surfactant apoprotein and Clara cell antigen. Rat surfactant apoprotein immunostaining was detected in type II pneumocytes in sections of normal lung, in the cells of the prolif erative lesions classified histologically as alveolar epithelial hyper plasia (51) and mixed foci (alveolar epithelial hyperplasia with fibro sis) (30), and in adenomas (2), adenocarcinomas (3), and adenosquamous carcinomas (2). With the exception of one adenosquamous carcinoma, Cl ara cell antigen immunostaining was not detected in any of the pulmona ry lesions but was detected in nonciliated cuboidal epithelial (Clara) cells in normal bronchioles. The epithelial cells of the proliferativ e lesions and neoplasms had ultrastructural features consistent with t ype II pneumocytes, i.e., the presence of cytoplasmic lamellar and mul tivesicular bodies. The results of these studies indicate that the maj ority of plutonium-induced proliferative epithelial lesions and neopla sms in the rat originate from alveolar type II pneumocytes.