Inactivation of p53 in normal human cells increases G2/M arrest and sensitivity to DNA-damaging agents
✍ Scribed by Jocelyn Céraline; Gaël Deplanque; Brigitte Duclos; Jean-Marc Limacher; Amor Hajri; Francine Noel; Christophe Orvain; Thierry Frébourg; Claudine Klein-Soyer; Jean-Pierre Bergerat
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- French
- Weight
- 206 KB
- Volume
- 75
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
p53 mutations are found in about 70% of human cancers. In order to evaluate the role of these mutations in response to chemotherapeutic agents, it is important to distinguish between p53 response to DNA-damaging agents in normal and in tumour cells. Here, using normal human fibroblasts (NHFs), we show that cisplatin and UV radiation induce G 2 /M arrest which is temporally linked to p53-protein induction. To study the contribution of p53 to this G 2 /M arrest, we inhibited p53 induction in NHFs using p53 anti-sense oligonucleotides. Following exposure of NHFs to UV radiation, the inhibition of p53-protein induction leads to a greater accumulation of cells in the G 2 /M phase, but also to a decreased fraction of cells in the G 1 phase. We propose that p53 does not induce G 2 /M arrest directly, and that the extent of this arrest may depend on the fraction of cells that do not stop at the G 1 phase following exposure to DNA-damaging agents. Furthermore, inhibition of p53-protein induction leads to increased sensitivity of NHFs to UV radiation. These results suggest that inhibition of p53 protein enhances sensitivity to DNAdamaging agents in normal human cells.