The type II pneumocyte cell cycle was studied in vivo and in vitro thr
ough bivariate flow cytometric analysis of DNA content vs. incorporate
d 5-bromo-2-deoxyuridine (BrdUrd). The cell cycle phase durations T-s
(7.8 h) and T-G2/M (1.1 h), measured in vivo, agreed well with earlier
estimates obtained by thymidine labeling. Left unilateral pneumonecto
my increased the BrdUrd labeling index of type II cells in the remaini
ng lung from an initial value of 1.9 +/- 0.3% to 4.8 +/- 1.0%, but had
no effect on T-s or T-G2/M in vivo. In both normal and pneumonectomiz
ed animals, BrdUrd-positive cells in vivo rapidly completed mitosis bu
t did not enter a second S-phase. These results demonstrate that proli
ferating type II cells do not form a continuously cycling population i
n the normal or regenerating adult lung. When cell cycle parameters we
re measured in vitro immediately after type II cell isolation, T-s inc
reased a-fold and T-G2/M rose up to 10-fold above the value obtained i
n vivo. After 2 d of primary culture under customary plating condition
s, T-s had returned to the same value as that in vivo, but T-GB/M rema
ined elevated. Little variability was observed in the duration of S-ph
ase within each treatment group. In contrast, type II cells exhibited
considerable heterogeneity in the rate of G2/M-phase traverse, especia
lly in vitro. These data suggest that the inability of adult rat type
II pneumocytes to proliferate in primary culture is related to delayed
G2/M-phase transit and imply the existence of pneumocyte subpopulatio
ns which differ in susceptibility to growth arrest. (C) 1994 Wiley-Lis
s, Inc.