Alteration in cell proliferation in mouse lung following urethane exposure. II. Effects of chronic exposure on terminal bronchiolar epithelium.

Cell proliferation in bronchiolar epithelium of normal mouse lung and of lung chronically exposed to urethane was compared. Animals treated for 10 weeks with drinking water containing 0.1% urethane and their controls were injected with (3)H-thymidine; autoradiographs were made of lung tissue and mean grain counts of labeled nuclei in terminal bronchiolar epithelium compared in the control and urethane-treated groups. In controls, the decline in mean grain counts of labeled daughter cells between 24 hours and 4 days after (3)H-thymidine injection was compatible with a mean cell cycle time of about 60 hours. In contrast, the hyperplastic bronchiolar epithelium of the urethane-treated animals showed an elevated labeling index and deficient production of labeled cells over the 6-day period as judged by decline in mean grain counts. These findings were interpreted as showing that the hyperplasia and high labeling index did not represent faster turnover or shortened cycle but reflected an increase in cell cycle time or of population renewal time.