Visualization of complex DNA double-strand breaks in a tumor treated with carbon ion radiotherapy

Sci Rep. 2016 Mar 1;6:22275. doi: 10.1038/srep22275.

Abstract

Carbon ion radiotherapy shows great potential as a cure for X-ray-resistant tumors. Basic research suggests that the strong cell-killing effect induced by carbon ions is based on their ability to cause complex DNA double-strand breaks (DSBs). However, evidence supporting the formation of complex DSBs in actual patients is lacking. Here, we used advanced high-resolution microscopy with deconvolution to show that complex DSBs are formed in a human tumor clinically treated with carbon ion radiotherapy, but not in a tumor treated with X-ray radiotherapy. Furthermore, analysis using a physics model suggested that the complexity of radiotherapy-induced DSBs is related to linear energy transfer, which is much higher for carbon ion beams than for X-rays. Visualization of complex DSBs in clinical specimens will help us to understand the anti-tumor effects of carbon ion radiotherapy.

Publication types

  • Case Reports
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biopsy
  • Cell Death / radiation effects
  • DNA / ultrastructure*
  • DNA Breaks, Double-Stranded* / radiation effects
  • Female
  • Heavy Ion Radiotherapy*
  • Humans
  • Linear Energy Transfer
  • Microscopy
  • Tumor Burden / radiation effects
  • Tumor Suppressor p53-Binding Protein 1 / immunology
  • Uterine Cervical Neoplasms / radiotherapy*
  • Uterine Cervical Neoplasms / ultrastructure
  • X-Ray Therapy

Substances

  • TP53BP1 protein, human
  • Tumor Suppressor p53-Binding Protein 1
  • DNA