Considerable attention has recently been focused on the fact that the
tumor suppressor protein p53 is involved in the cellular response to r
adiation. In its wild-type form the protein appears to control a cell
cycle checkpoint, preventing entry into S-phase following DNA damage.
A number of authors observed a radiation induced G(1)-block in cells e
xpressing wild-type p53, but not in p53 mutant cells. We obtained simi
lar results with four human tumour cell lines as well as two strains o
f human fibroblasts, whose p53 status was ascertained at the protein a
s well as DNA levels. In addition to cell cycle delays in exponentiall
y growing cell cultures, we have studied the possible role of the p53
in the transition from quiescence to active proliferation. Cells were
irradiated after 6 days of serum-starvation and labelled with BrdU at
different times after addition of fresh medium. Entry into S-phase was
found to be delayed by several hours in the p53 wild-type cells, but
no such effect was observed in the p53 mutants. Where a delay occurred
, it was roughly proportional to the X-ray dose. Although it remains t
o be clarified, whether the cells were delayed only in G(1) or also in
G(0), it is interesting to note that entry into S-phase can be delaye
d by irradiation in a quiescent state immediately before serum-stimula
tion, provided the cells are wild-type with respect to p53. Certain di
fferences in the cell cycle response of transformed and untransformed
cells were noted.