Differences in DNA Repair Capacity, Cell Death and Transcriptional Response after Irradiation between a Radiosensitive and a Radioresistant Cell Line

Sci Rep. 2016 Jun 1;6:27043. doi: 10.1038/srep27043.

Abstract

Normal tissue toxicity after radiotherapy shows variability between patients, indicating inter-individual differences in radiosensitivity. Genetic variation probably contributes to these differences. The aim of the present study was to determine if two cell lines, one radiosensitive (RS) and another radioresistant (RR), showed differences in DNA repair capacity, cell viability, cell cycle progression and, in turn, if this response could be characterised by a differential gene expression profile at different post-irradiation times. After irradiation, the RS cell line showed a slower rate of γ-H2AX foci disappearance, a higher frequency of incomplete chromosomal aberrations, a reduced cell viability and a longer disturbance of the cell cycle when compared to the RR cell line. Moreover, a greater and prolonged transcriptional response after irradiation was induced in the RS cell line. Functional analysis showed that 24 h after irradiation genes involved in "DNA damage response", "direct p53 effectors" and apoptosis were still differentially up-regulated in the RS cell line but not in the RR cell line. The two cell lines showed different response to IR and can be distinguished with cell-based assays and differential gene expression analysis. The results emphasise the importance to identify biomarkers of radiosensitivity for tailoring individualized radiotherapy protocols.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological
  • B-Lymphocytes / cytology
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / radiation effects*
  • Cell Cycle / genetics
  • Cell Cycle / radiation effects*
  • Cell Death / radiation effects
  • Cell Line, Transformed
  • Cell Survival / radiation effects
  • DNA Damage
  • DNA Repair / radiation effects*
  • Dose-Response Relationship, Radiation
  • Gamma Rays / adverse effects
  • Gene Expression Profiling
  • Gene Expression Regulation / radiation effects*
  • Histones / genetics
  • Histones / metabolism
  • Humans
  • Molecular Sequence Annotation
  • Radiation Tolerance
  • Signal Transduction
  • Transcription, Genetic / radiation effects*
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • H2AX protein, human
  • Histones
  • Tumor Suppressor Protein p53