Inactivation of p53 in normal human cells increases G2/M arrest and sensitivity to DNA-damaging agents

Int J Cancer. 1998 Jan 30;75(3):432-8. doi: 10.1002/(sici)1097-0215(19980130)75:3<432::aid-ijc17>;2-a.


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 G2/M arrest which is temporally linked to p53-protein induction. To study the contribution of p53 to this G2/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 G2/M phase, but also to a decreased fraction of cells in the G1 phase. We propose that p53 does not induce G2/M arrest directly, and that the extent of this arrest may depend on the fraction of cells that do not stop at the G1 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 DNA-damaging agents in normal human cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Base Sequence
  • Cells, Cultured
  • Cisplatin / pharmacology*
  • DNA / drug effects
  • DNA / metabolism
  • DNA / radiation effects
  • DNA Damage*
  • Drug Screening Assays, Antitumor
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Fibroblasts / radiation effects
  • G2 Phase / drug effects
  • G2 Phase / physiology*
  • G2 Phase / radiation effects
  • Gene Expression Regulation / physiology*
  • Genes, p53*
  • Humans
  • Mitosis / drug effects
  • Mitosis / physiology*
  • Mitosis / radiation effects
  • Molecular Sequence Data
  • Mutation
  • Oligonucleotides, Antisense / pharmacology*
  • Radiation Tolerance / physiology*
  • Tumor Suppressor Protein p53 / biosynthesis
  • Ultraviolet Rays / adverse effects


  • Antineoplastic Agents
  • Oligonucleotides, Antisense
  • Tumor Suppressor Protein p53
  • DNA
  • Cisplatin

Associated data

  • GENBANK/X01405
  • GENBANK/X52470