Role of Rad52 in fractionated irradiation induced signaling in A549 lung adenocarcinoma cells

Mutat Res. 2012 Jan 3;729(1-2):61-72. doi: 10.1016/j.mrfmmm.2011.09.007. Epub 2011 Oct 4.

Abstract

The effect of fractionated doses of γ-irradiation (2Gy per fraction over 5 days), as delivered in cancer radiotherapy, was compared with acute doses of 10 and 2Gy, in A549 cells. A549 cells were found to be relatively more radioresistant if the 10Gy dose was delivered as a fractionated regimen. Microarray analysis showed upregulation of DNA repair and cell cycle arrest genes in the cells exposed to fractionated irradiation. There was intense activation of DNA repair pathway-associated genes (DNA-PK, ATM, Rad52, MLH1 and BRCA1), efficient DNA repair and phospho-p53 was found to be translocated to the nucleus of A549 cells exposed to fractionated irradiation. MCF-7 cells responded differently in fractionated regimen. Silencing of the Rad52 gene in fractionated group of A549 cells made the cells radiosensitive. The above result indicated increased radioresistance in A549 cells due to the activation of Rad52 gene.

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma of Lung
  • Cell Cycle Checkpoints / radiation effects
  • Cell Line, Tumor / radiation effects
  • DNA Repair / radiation effects
  • DNA-Activated Protein Kinase / genetics
  • DNA-Activated Protein Kinase / radiation effects
  • Dose Fractionation, Radiation
  • Dose-Response Relationship, Radiation
  • Gamma Rays
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Gene Silencing
  • Humans
  • Lung Neoplasms / metabolism*
  • Oligonucleotide Array Sequence Analysis
  • Rad52 DNA Repair and Recombination Protein / genetics*
  • Rad52 DNA Repair and Recombination Protein / metabolism
  • Radiation Tolerance / genetics
  • Signal Transduction / radiation effects*
  • Up-Regulation / radiation effects

Substances

  • RAD52 protein, human
  • Rad52 DNA Repair and Recombination Protein
  • DNA-Activated Protein Kinase