ABSENCE OF RADIATION-INDUCED G(1) ARREST IN 2 CLOSELY-RELATED HUMAN LYMPHOBLAST CELL-LINES THAT DIFFER IN P53 STATUS

In order to examine more precisely the role of p53 in the activation o f the G(1)/S checkpoint by ionizing radiation, we examined two human l ymphoblast cell lines derived from the same donor. The TK6 line had a doubling time of 12.2 h and expressed wild type p53, while the WTK1 li ne had a doubling time of 12.7 h and expressed mutant p53, The two lin es differ significantly in their susceptibility to radiation-induced c ell killing and apoptosis, Cells were examined by flow cytometry at re gular intervals from 0 to 12 h after irradiation with two different do ses designed to yield equivalent survival levels in both cell lines. I n some experiments, cells were incubated with colcemid to block them i n the first postirradiation mitosis and prevent contamination of the f low cytometric profiles with second cycle cells. There was no signific ant difference between the two cell lines in the progression of irradi ated cells out of G(1) and into the S and G(2) phases of the cell cycl e, In particular, there was no evidence for a prolonged arrest in G(1) in the TK6 cell line expressing wild type p53, Furthermore, expressio n of the p53 downstream genes WAF1/CIP1 and RE appeared normal in TK6 cells, These results suggest that factors other than those in the p53 signal transduction pathway alone may be required to activate the G(1) /S checkpoint in irradiated human cells and that apoptosis and G(1) ar rest may utilize different pathways.