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

• Published in: Medical physics (Lancaster) 2020-01, Vol.47 (1), p.272-281
• Main Authors: McFadden, Conor H., Rahmanian, Shirin, Flint, David B., Bright, Scott J., Yoon, David S., O’Brien, Daniel J., Asaithamby, Aroumougame, Abdollahi, Amir, Greilich, Steffen, Sawakuchi, Gabriel O.
• Format: Article
• Language: English
• Subjects: DNA damage response; DNA repair; fluorescent nuclear track detectors; live cell imaging; particle therapy
• ISSN: 0094-2405; 2473-4209
• DOI: 10.1002/mp.13897

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.