Functional inactivation of p53 by HPV-E6 transformation is associated with a reduced expression of radiation-induced potentially lethal damage

Int J Radiat Biol. 1999 Mar;75(3):285-91. doi: 10.1080/095530099140465.

Abstract

Purpose: To examine the effect of functional loss of p53 on radiation sensitivity and potentially lethal damage repair (PLDR).

Materials and methods: Radiation sensitivity and PLDR were examined in an isogenic pair of human tumour cell lines created by HPV-E6 transformation.

Results: Inactivation of p53 by E6 transformation resulted in a cell line that was more resistant to killing by radiation but showed little enhancement in survival (PLDR) when plateau-phase cells were held non-cycling after radiation exposure. Holding p53-normal cells in plateau-phase after radiation exposure not only led to enhanced survival, but also to a reduction in the proportion of cells that blocked in G1 subsequent to release.

Conclusions: These results suggest that p53 expression influences that component of radiation sensitivity associated with PLDR.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology
  • Adenocarcinoma / virology*
  • Cell Survival / radiation effects
  • Cell Transformation, Viral / genetics*
  • Gene Expression Regulation, Neoplastic / radiation effects*
  • Genes, p53*
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Lung Neoplasms / virology*
  • Neoplasms, Radiation-Induced / genetics
  • Neoplasms, Radiation-Induced / pathology
  • Neoplasms, Radiation-Induced / virology
  • Oncogene Proteins, Viral / genetics*
  • Papillomaviridae / genetics*
  • Radiation Tolerance
  • Repressor Proteins*
  • Tumor Cells, Cultured

Substances

  • E6 protein, Human papillomavirus type 16
  • Oncogene Proteins, Viral
  • Repressor Proteins