title: The yield of DNA double strand breaks determined after exclusion of those forming from heat-labile lesions predicts tumor cell radiosensitivity to killing.
abstract: OBJECTIVE
  The radiosensitivity to killing of tumor cells and in-field normal tissue are key determinants of radiotherapy response. In vitro radiosensitivity of tumor- and normal-tissue-derived cells often predicts radiation response, but high determination cost in time and resources compromise utility as routine response-predictor. Efforts to use induction or repair of DNA double-strand-breaks (DSBs) as surrogate-predictors of cell radiosensitivity to killing have met with limited success. Here, we re-visit this issue encouraged by our recent observations that ionizing radiation (IR) induces not only promptly-forming DSBs (prDSBs), but also DSBs developing after irradiation from the conversion to breaks of thermally-labile sugar-lesions (tlDSBs).
  
  
  METHODS
  We employ pulsed-field gel-electrophoresis and flow-cytometry protocols to measure total DSBs (tDSB=prDSB+tlDSBs) and prDSBs, as well as γH2AX and parameters of chromatin structure.
  
  
  RESULTS
  We report a fully unexpected and in many ways unprecedented correlation between yield of prDSBs and radiosensitivity to killing in a battery of ten tumor cell lines that is not matched by yields of tDSBs or γH2AX, and cannot be explained by simple parameters of chromatin structure.
  
  
  CONCLUSIONS
  We propose the introduction of prDSBs-yield as a novel and powerful surrogate-predictor of cell radiosensitivity to killing with potential for clinical application.
authors: Institute of Medical Radiation Biology, University of Duisburg-Essen Medical School, Germany.
authors: Yanlei
authors: Y
authors: Cheng
authors: Institute of Medical Radiation Biology, University of Duisburg-Essen Medical School, Germany.
authors: Fanghua
authors: F
authors: Li
authors: Institute of Medical Radiation Biology, University of Duisburg-Essen Medical School, Germany.
authors: Emil
authors: E
authors: Mladenov
authors: Institute of Medical Radiation Biology, University of Duisburg-Essen Medical School, Germany. Electronic address: Georg.Iliakis@uk-essen.de.
authors: George
authors: G
authors: Iliakis
mesh_terms: D045744:Cell Line, Tumor; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects*; D016521:Electrophoresis, Gel, Pulsed-Field; D005260:Female; D005434:Flow Cytometry; D006358:Hot Temperature; D006801:Humans; D008297:Male; D011836:Radiation Tolerance / Q000235:genetics / Q000502:physiology* / Q000528:radiation effects
keywords: DNA double strand breaks (DSB); Heat labile lesions; Ionizing radiation (IR); Predictive assays