Assessment of DNA damage produced by 125I-triplex-forming oligonucleotides in cells

Int J Radiat Biol. 2004 Nov-Dec;80(11-12):927-31. doi: 10.1080/09553000400017648.


Purpose: Triplex-forming oligodeoxyribonucleotides (TFOs) bind specifically to their target sequences by forming hydrogen bonds within the major groove of the target duplex. When labeled with Auger-electron-emitting radioisotopes, TFOs are able to damage the target gene in a process named antigene radiotherapy. We compared radiotoxicity and the amount of DNA damage produced within cultured cells by two 125I-labeled TFOs, one with a single target in the genome and another with multiple targets.

Materials and methods: Radiotoxicity was measured by clonogenic assay while DNA damage was assessed by the number of histone gamma-H2AX foci formed at the sites of DNA double strand breaks (DSBs).

Results: The TFO with multiple nuclear targets was 1.7 fold more radiotoxic and produced on average 1.9 fold more gamma-H2AX foci per cell than the TFO with a single target.

Conclusion: Since the two methods gave comparable results, measuring the number of gamma-H2AX foci per decay may be a useful procedure for the assessment of cytotoxic effects and the intranuclear localization of radionuclides when they produce DSBs.

Publication types

  • Comparative Study

MeSH terms

  • Cell Line
  • Cell Line, Tumor / radiation effects
  • Cell Survival / radiation effects*
  • DNA / adverse effects*
  • DNA / radiation effects*
  • DNA / ultrastructure
  • DNA Damage*
  • Dose-Response Relationship, Radiation
  • Fibrosarcoma / genetics
  • Fibrosarcoma / metabolism
  • Fibrosarcoma / pathology*
  • Histones / genetics
  • Histones / metabolism
  • Humans
  • Iodine Radioisotopes / adverse effects*
  • Radiation Dosage
  • Radiopharmaceuticals / adverse effects


  • H2AX protein, human
  • Histones
  • Iodine Radioisotopes
  • Radiopharmaceuticals
  • triplex DNA
  • DNA