Dosimetry of heavy ion exposure to human cells using nanoscopic imaging of double strand break repair protein clusters

0554301 - ÚJF 2023 RIV DE eng J - Journal Article
Reindl, J. - Kundrát, Pavel - Girst, S. - Sammer, M. - Schwarz, B. - Dollinger, G.
Dosimetry of heavy ion exposure to human cells using nanoscopic imaging of double strand break repair protein clusters.
Scientific Reports. Roč. 12, č. 1 (2022), č. článku 1305. ISSN 2045-2322. E-ISSN 2045-2322
Institutional support: RVO:61389005
Keywords : high-LET particles * DNA damage * tumor therapy methods
OECD category: Radiology, nuclear medicine and medical imaging
Impact factor: 4.6, year: 2022
Method of publishing: Open access
https://doi.org/10.1038/s41598-022-05413-6

The human body is constantly exposed to ionizing radiation of different qualities. Especially the exposure to high-LET (linear energy transfer) particles increases due to new tumor therapy methods using e.g. carbon ions. Furthermore, upon radiation accidents, a mixture of radiation of different quality is adding up to human radiation exposure. Finally, long-term space missions such as the mission to mars pose great challenges to the dose assessment an astronaut was exposed to. Currently, DSB counting using gamma H2AX foci is used as an exact dosimetric measure for individuals. Due to the size of the gamma H2AX IRIF of similar to 0.6 mu m, it is only possible to count DSB when they are separated by this distance. For high-LET particle exposure, the distance of the DSB is too small to be separated and the dose will be underestimated. In this study, we developed a method where it is possible to count DSB which are separated by a distance of similar to 140 nm. We counted the number of ionizing radiation-induced pDNA-PKcs (DNA-PKcs phosphorylated at T2609) foci (size = 140 nm +/- 20 nm) in human HeLa cells using STED super-resolution microscopy that has an intrinsic resolution of 100 nm. Irradiation was performed at the ion microprobe SNAKE using high-LET 20 MeV lithium (LET= 116 keV/mu m) and 27 MeV carbon ions (LET= 500 keV/mu m). pDNA-PKcs foci label all DSB as proven by counterstaining with 53BP1 after low-LET gamma-irradiation where separation of individual DSB is in most cases larger than the 53BP1 gross size of about 0.6 mu m. Lithium ions produce (1.5 +/- 0.1) IRIF/mu m track length, for carbon ions (2.2 +/- 0.2) IRIF/mu m are counted. These values are enhanced by a factor of 2-3 compared to conventional foci counting of high-LET tracks. Comparison of the measurements to PARTRAC simulation data proof the consistency of results. We used these data to develop a measure for dosimetry of high-LET or mixed particle radiation exposure directly in the biological sample. We show that proper dosimetry for radiation up to a LET of 240 keV/mu m is possible.
Permanent Link: http://hdl.handle.net/11104/0328935