Proliferation of mouse lung epithelial cells after inhalation exposure to 239PuO2

The aim of this study was to investigate cell proliferation in mouse lungs up to 12 weeks after exposure to 239PuO2. CBA mice were exposed (nose-only) to 239PuO2 to give an initial alveolar deposit of 500 Bq. The main morphological change observed was hypertrophy of Type II cells. The labeling index (LI) of alveolar cells, which was monitored by immunocytochemical detection of DNA-incorporated 5-bromo-2'-deoxyuridine (BrdU), increased with time after exposure and was eight times that of controls by the end of the study. The LI of the bronchiolar cells was increased markedly after exposure but declined thereafter. The cell proliferation patterns of the alveolar and bronchiolar cells (mainly Type II and Clara cells, respectively) could be related to the distribution and clearance patterns of the deposited particles of 239PuO2 and to the effects of alpha-particle radiation on these cells. This study showed that significant cellular changes, particularly cell proliferation, occurred at early times after exposure of mouse lung to 239PuO2. However, the relevance of these results to the late carcinogenic effects of 239Pu could not be assessed because of the limited duration of this study.