Abstract

The inhibition of replicative DNA synthesis, in which p53 has a pivotal role, is an important component of the cellular response to radiation-induced DNA damage. In this study we have examined the relationship between p53 levels before and after irradiation, radiation-induced cell cycle delays and radiosensitivity in a panel of 8 human tumour cell lines. The cell lines differed widely in their clonogenic survival after radiation, (SF2=0.18–0.82). Constitutive p53 protein levels varied from 2.2±0.4 to 6.3±0.3 OD units per 10<sup>6</sup> cells. p53 after irradiation (6 Gy) also varied among the cell lines, ranging from no induction to a 1.6 fold increase in p53 levels 4 hours after treatment. Overall cellular radiosensitivity correlates well with the level of radiation-induced Gl arrest (r=0.856, <i>P</i>=0.0067), with p53 constitutive levels (r=0.874, <i>P</i>=0.0046) and with p53 protein fold induction (r=–0.882, <i>P</i>=0.0038). The mechanistic basis of these correlations remains to be elucidated in these cells, but the data do suggest that both the constitutive p53 level, and the p53 protein response to radiation, may be good predictive tests for radiosensitivity in some cell types.

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