RADIATION-INDUCED G(1)-BLOCK AND P53 STATUS IN 6 HUMAN CELL-LINES

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.