Isolation of time-dependent DNA damage induced by energetic carbon ions and their fragments using fluorescent nuclear track detectors

Conor H. McFadden, Shirin Rahmanian, David B. Flint, Scott J. Bright, David S. Yoon, Daniel J. O’Brien, Aroumougame Asaithamby, Amir Abdollahi, Steffen Greilich, Gabriel O. Sawakuchi

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: High energetic carbon (C-) ion beams undergo nuclear interactions with tissue, producing secondary nuclear fragments. Thus, at depth, C-ion beams are composed of a mixture of different particles with different linear energy transfer (LET) values. We developed a technique to enable isolation of DNA damage response (DDR) in mixed radiation fields using beam line microscopy coupled with fluorescence nuclear track detectors (FNTDs). Methods: We imaged live cells on a coverslip made of FNTDs right after C-ion, proton or photon irradiation using an in-house built confocal microscope placed in the beam path. We used the FNTD to link track traversals with DNA damage and separated DNA damage induced by primary particles from fragments. Results: We were able to spatially link physical parameters of radiation tracks to DDR in live cells to investigate spatiotemporal DDR in multi-ion radiation fields in real time, which was previously not possible. We demonstrated that the response of lesions produced by the high-LET primary particles associates most strongly with cell death in a multi-LET radiation field, and that this association is not seen when analyzing radiation induced foci in aggregate without primary/fragment classification. Conclusions: We report a new method that uses confocal microscopy in combination with FNTDs to provide submicrometer spatial-resolution measurements of radiation tracks in live cells. Our method facilitates expansion of the radiation-induced DDR research because it can be used in any particle beam line including particle therapy beam lines. Category: Biological Physics and Response Prediction.

Original languageEnglish (US)
Pages (from-to)272-281
Number of pages10
JournalMedical physics
Volume47
Issue number1
DOIs
StatePublished - Jan 1 2020

Keywords

  • DNA damage response
  • DNA repair
  • fluorescent nuclear track detectors
  • live cell imaging
  • particle therapy

ASJC Scopus subject areas

  • Biophysics
  • Radiology Nuclear Medicine and imaging

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