Impact of p210(Bcr-Abl) on ultraviolet C wavelength-induced DNA damage and repair

Clin Cancer Res. 2003 Sep 1;9(10 Pt 1):3722-30.

Abstract

Recently, it was shown that both Bcr and Bcr-Abl can interact with xeroderma pigmentosum group B (XPB/ERCC3), a protein implicated in DNA repair after UV-induced damage. To further analyze the effect of Bcr-Abl on the DNA damage response, we used cell lines stably transfected with the BCR-ABL gene and their parental counterparts (MBA-1 versus MO7E and Bcr-AblT1 versus 4A2(+)-pZAP) and several assays reflecting DNA repair: the comet assay, a radioimmunoassay for cyclobutane pyrimidine dimers, and clonogenic assays. After exposure to UVC (0.5-5.0 joules m(-2)), the Comet assay demonstrated greater efficiency of DNA repair in the BCR-ABL-positive cells (both MBA-1 and Bcr-AblT1) when compared with their parental counterparts. Furthermore, there was less production of the UV-induced DNA adduct-cyclobutane pyrimidine dimers-as well as a more rapid rate of disappearance of these adducts and greater UV survival (clonogenic assays) in MBA-1 cells as compared with MO7E cells. Apoptosis (annexin V-FITC/propidium iodide staining) was markedly reduced in the BCR-ABL-positive cells. These results indicate that BCR-ABL confers enhanced resistance to UV radiation-induced damage and increased efficiency of DNA repair and that these changes are associated with a protective antiapoptotic effect.

MeSH terms

  • Annexin A5 / pharmacology
  • Apoptosis
  • Cell Line
  • Comet Assay
  • DNA Damage / drug effects*
  • DNA Repair / drug effects*
  • Dimerization
  • Enzyme Inhibitors / pharmacology
  • Fluorescein-5-isothiocyanate / pharmacology
  • Fusion Proteins, bcr-abl / genetics
  • Fusion Proteins, bcr-abl / therapeutic use*
  • Genetic Vectors
  • Humans
  • Pyrimidine Dimers / chemistry
  • Radioimmunoassay
  • Time Factors
  • Transfection
  • Ultraviolet Rays*

Substances

  • Annexin A5
  • Enzyme Inhibitors
  • Pyrimidine Dimers
  • Fusion Proteins, bcr-abl
  • Fluorescein-5-isothiocyanate