RELATIONSHIP BETWEEN P53 STATUS AND RADIOSENSITIVITY IN HUMAN TUMOR-CELL LINES

We examined the relationship between p53 levels before and after irrad iation, radiation-induced cell cycle delays, apoptotic cell death and radiosensitivity in a panel of eight human tumour cell lines. The cell lines differed widely in their clonogenic survival after radiation, ( surviving Fraction at 2 Gy: SF2=0.18-0.82). Constitutive p53 protein l evels varied from 2.2 +/- 0.4 to 6.3 +/- 0.3 optical density units (OD ) per 10(6) cells, p53 after irradiation (6 Gy) also varied between th e cell lines, ranging from no induction to a 1.6-fold increase in p53 levels 4 h after treatment. p53 function was also assessed by G(1) cel l cycle arrest after irradiation. The cellular response to radiation, measured as G(0)/G(1) arrest, and the induction of apoptosis were in g ood agreement. However, a trace amount of DNA ladder formation was fou nd in two cell lines lacking G(1) arrest. Overall cellular radiosensit ivity correlated well with the level of radiation-induced G(1) arrest (correlation coefficient r=0.856; P=0.0067), with p53 constitutive lev els (r=0.874, P=0.0046), and with p53 protein fold induction (r=-0.882 , P=0.0038). Our data suggest that (1) the constitutive p53 level, (2) G(1) arrest after irradiation, or (3) the p53 protein response to rad iation may be good predictive tests for radiosensitivity in some cell types.