Kinetics of pulmonary epithelial proliferation during prenatal growth of the mouse lung

Autoradiographic methods were used to analyze cell kinetics in peripheral epithelium of the fetal mouse lung, days 15-18. The 3H labeling index decreased in proportion to increases in fetal lung and body weight from day 15 to day 18. Cell-cycle determination estimated from the percent of labeled metaphases at intervals after 3H thymidine injection showed the shortest cell-cycle time (12.25 hours) on day 15 during the precanal stage of growth. Total cycle time (Tc) increased by approximately one hour on each subsequent day. Between days 15 and 16 Tc increased due to a 1-hour increase in the post mitotic interphase (G1); thereafter, increases in Tc could be ascribed almost entirely to lengthening of the DNA symthetic period. A comparison of cell-cycle time in central and peripheral tubules of the same lungs on day 15 showed a slower cell cycle in the central tubules than in the peripheral branches. An estimate of the growth fraction (GF) on each day based on calculated and ovserved cell-cycle time showed that GF was 1 on days 15 and 16, decreasing to 0.69 on day 17 and 0.27 on day 18. Thus cell-cycle time increases with lung maturation and it increases from peripheral to central zones of the bronchial tree. The greater part of the observed decline in growth rate as the prenatal phase of growth is completed was due largely to a decrease in the fraction of cells in the cell cycle.