CELL-KINETICS OF URETHANE-INDUCED MURINE PULMONARY ADENOMATA .2. GROWTH FRACTION AND CELL LOSS FACTOR

Continuous labeling of urethane induced pulmonary adenomas in adult male A2G mice at intervals up to 20 wk showed that the growth fraction fell progressively from 18% at 7 wk to 7% at 20 wk. This fall appears to be responsible for the decrease in production of adenoma cells with age. A fraction labeled mitoses curve was constructed for pulmonary adenomas at 14 wk posturethane. Only the 1st peak was apparent, giving median t2 and ts values of 2 and 9 h respectively. The cell cycle time was calculated at 45 h and the growth fraction at 6.2%, while the cell loss factor was estimated at 31%. Other cell loss values were calculated from data on the rate of entry into DNA synthesis obtained previously by double labeling. These values remained constant with time at 83-95%, suggesting that cell loss is in some way linked to cell production. The development of polyploidy in adenoma cells could not be eliminated. No areas of necrosis were seen in the adenomas at any time although karyorrhexis occurred in isolated cells. The labeling characteristics of alveolar wall cells in the same lung sections as the adenomas did not vary with time and the continuous labeling curve gave a growth fraction of 1.8%, a DNA synthetic time of 10 h and a cell cycle time of 30 h.