54. Immunohistochemical Study on Cellular Origins of Rat Lung Tumors Induced by Inhalation Exposure to Plutonium Dioxide and by X-ray Irradiation
Yoichi Oghiso and Yutaka Yamada
Keywords: immunohistochemistry, rat, lung tumors, plutonium-exposure, X-ray irradiation
Immunohistochemical examinations were done on rat lung tumors induced by inhalation exposures to plutonium or by X-ray irradiation to identify and compare cellular origins or, in turn, target cells at risk for radiation carcinogenesis. Female Wistar (W/M) strain rats were either exposed to submicron-sized 239PuO2 aerosols, or irradiated locally or systemically by X-rays at 100 to 120 days after birth. Primary lung tumor specimens were selected for the present examinations from 135 plutonium-exposed and 41 X-ray irradiated rats. All of those lung tumors appeared to occur from the lower respiratory tract epithelium through bronchioles into alveoli and were histopathologically diagnosed as adenoma, adenocarcinoma, adenosquamous carcinoma, and squamous cell carcinoma. Immunohistochemical staining of neoplastic lesions using rabbit polyclonal antibodies to rat surfactant apoprotein A specific for alveolar type II pneumocytes and Clara cell antigen specific for nonciliated bronchiolar Clara cells, showed that most adenomatous and adenocarcinomatous lesions from plutonium-exposed or X-ray irradiated rats were positive for either or both antigens, while in contrast, adenosquamous and squamous lesions were mostly negative for both antigens. Even though there were some differences in the proportions and distributions of immunoreactive cells between plutonium- and X-ray-induced tumors and among neoplastic lesions, the results indicated that radiation-induced pulmonary adenomas and adenocarcinomas mostly originate from either alveolar type II pneumocytes or bronchiolar Clara cells, while adenosquamous and squamous carcinomas may be derived from other epithelial cell components, or might have lost specific antigenicity during their transforming differentiation.