The proliferation of normal non-tumourigenic mouse fibroblasts is stri
ngently controlled by regulatory mechanisms located in the postmitotic
stage of G(1) (which we have designated G(1)pm). Upon exposure to gro
wth factor depletion or a lowered de novo protein synthesis, the norma
l cells leave the cell cycle from G(1)pm and enter G(0). The G(1)pm ph
ase is characterized by a remarkably constant length (the duration of
which is 3 h in Swiss 3T3 cells), whereas the intercellular variabilit
y of intermitotic time is mainly ascribable to late G(1) or pre S phas
e (G(1)ps) (Zetterberg and Larsson (1985) Proc. Nail. Acad. Sci. USA 8
2, 5365). As shown in the present study two tumour-transformed derivat
ives of mouse fibroblasts, i.e. BPA31 and SVA31, did not respond at al
l, or only responded partially, respectively, to serum depletion and i
nhibition of protein synthesis. If the tumour cells instead were subje
cted to 25-hydroxycholesterol (an inhibitor of 3-hydroxy-3 methyglutar
yl coenzyme A reductase activity), their growth was blocked as measure
d by growth curves and [H-3]-thymidine uptake. Time-lapse analysis rev
ealed that the cells were blocked specifically in early G(1) (3-4h aft
er mitosis), and DNA cytometry confirmed that the arrested cells conta
ined a G(1) amount of DNA. Closer kinetic analysis revealed that the d
uration of the postmitotic phase containing cells responsive to 25-hyd
roxycholesterol was constant. These data suggest that transformed 3T3
cells also contain a 'G(1)pm program', which has to be completed befor
e commitment to mitosis. By repeating the experiments on a large numbe
r of tumour-transformed cells, including human carcinoma cells and gli
oma cells, it was demonstrated that all of them possessed a G(1)pm-lik
e stage. Our conclusion is that G(1)pm is a general phenomenon in mamm
alian cells, independent of whether the cells are normal or neoplastic
.