Tritiated thymidine-labeled bronchioloalveolar cells and radiation dose following inhalation of plutonium in rats.

The goal of this study is to show the relationship of inhaled Pu particle distribution and alveolar-bronchiolar target-cell response with respect to the formation of pulmonary carcinoma. The proliferation of type 2 alveolar epithelium and nonciliated bronchiolar epithelium appears critical in the induction of lung tumors associated from inhaled 239PuO2. Female, Wistar rats were either sham-exposed (40 rats) or given a single inhalation to 169Yb-239PuO2 (99 rats, ILB, 3.9 +/- 1.2 kBq) and examined at 20 time intervals from 1 day to 700 days postexposure for Pu particle distribution in airways by SEM quantitative autoradiography and for cell labeling with tritiated thymidine. Initially, deposited Pu particles were rapidly cleared from the surface of the trachea, bronchi, and bronchioles within a few days. Thereafter, about 5 times more alpha track exposure to the bronchiolar epithelium was delivered from Pu particles found in peribronchiolar alveoli than from Pu particles being cleared from bronchiolar surfaces. Exposure of bronchiolar epithelium at later times was due mostly to the formation of peribronchiolar Pu particle aggregates. A maximal increase in labeled alveolar wall cells was seen at 60 days after exposure, decreasing gradually to control levels by 400 days. Cell labeling in focal alveolar regions of Pu aggregation was about 5 fold higher. Increased bronchiolar epithelium labeling appeared in two phases. The first phase was seen 15 days after exposure, associated with initial deposition and clearance of Pu particles. The second phase slowly reached a maximum at 250 days and was associated with peribronchiolar Pu aggregate formation. The temporal-spatial dose-distribution pattern for inhaled Pu particles is an important aspect of Pu-induced pulmonary carcinogenesis.