Particles with similar LET values generate DNA breaks of different complexity and reparability: a high-resolution microscopy analysis of gamma H2AX/53BP1 foci

0492530 - BFÚ 2019 RIV GB eng J - Článek v odborném periodiku
Ježková, L. - Zadneprianetc, M. - Kulikova, E. - Smirnova, E. - Bulanova, T. - Depeš, Daniel - Falková, Iva - Boreyko, A. - Krasavin, E. - Davídková, Marie - Kozubek, Stanislav - Valentová, O. - Falk, Martin
Particles with similar LET values generate DNA breaks of different complexity and reparability: a high-resolution microscopy analysis of gamma H2AX/53BP1 foci.
Nanoscale. Roč. 10, č. 3 (2018), s. 1162-1179. ISSN 2040-3364. E-ISSN 2040-3372
Grant CEP: GA ČR(CZ) GA16-12454S; GA MZd NV16-29835A
Institucionální podpora: RVO:68081707 ; RVO:61389005
Klíčová slova: double-strand breaks * linear-energy-transfer * transmission electron-microscopy * induced chromosome-aberrations * histone h2ax phosphorylation
Obor OECD: Biophysics; Nuclear physics (UJF-V)
Impakt faktor: 6.970, rok: 2018

Biological effects of high-LET (linear energy transfer) radiation have received increasing attention, particularly in the context of more efficient radiotherapy and space exploration. Efficient cell killing by high-LET radiation depends on the physical ability of accelerated particles to generate complex DNA damage, which is largely mediated by LET. However, the characteristics of DNA damage and repair upon exposure to different particles with similar LET parameters remain unexplored. We employed high-resolution confocal microscopy to examine phosphorylated histone H2AX (gamma H2AX)/p53-binding protein 1 (53BP1) focus streaks at the microscale level, focusing on the complexity, spatiotemporal behaviour and repair of DNA double-strand breaks generated by boron and neon ions accelerated at similar LET values (similar to 135 keV mu m(-1)) and low energies (8 and 47 MeV per n, respectively). Cells were irradiated using sharp-angle geometry and were spatially (3D) fixed to maximize the resolution of these analyses. Both high-LET radiation types generated highly complex gamma H2AX/53BP1 focus clusters with a larger size, increased irregularity and slower elimination than low-LET gamma-rays. Surprisingly, neon ions produced even more complex gamma H2AX/53BP1 focus clusters than boron ions, consistent with DSB repair kinetics. Although the exposure of cells to gamma-rays and boron ions eliminated a vast majority of foci (94% and 74%, respectively) within 24 h, 45% of the foci persisted in cells irradiated with neon. Our calculations suggest that the complexity of DSB damage critically depends on (increases with) the particle track core diameter. Thus, different particles with similar LET and energy may generate different types of DNA damage, which should be considered in future research.
Trvalý link: http://hdl.handle.net/11104/0286030