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DNA damage and repair after exposure to ionizing radiation with different linear energy transfer

Ježková  Lucie, Ing., Ph.D. Istitute of Chemical Technology Prague


Scientific journal
Dissertation thesis at the UCT in Prague

Ionizing radiation is a very efficient way how to damage biological structures and tissue. Linear energy transfer (LET) is one of the characteristics of the radiation and it defines the amount of energy transferred to the surrounding environment per unit of distance. The efficiency of the radiation and its unique ability to cause complex DNA damage leading to more effective induction of mutations,
chromosomal aberrations or cell death, usually increases with the increasing LET value. The question of how extensive and complex DNA damage is induced by ionizing radiation with different LET values, and to which extent can an exposed can eliminate such damage correctly remains unanswered. We were focused on the characterization of the impact of the radiation with different LET values on the degree of DNA damage and its repair in normal human fibroblasts. The immunofluorescence detection of ionizing-radiation induced γH2AX/53BP1 foci formed in the sites of DNA double-strand breaks (DSB) has been used for the analysis. This method together with the advantages of high-resolution
confocal microscopy and detailed 3D analysis of γH2AX/53BP1 foci represent highly efficient utility for the description of a damage on a microscopic level in situ. For the evaluation of how the degree of damage correlates with the cell response, the observations have been supplemented by the detection of the programmed cell death induction - apoptosis. Using eight types of ionizing radiation we observed significant impact of LET on the degree of DNA damage complexity that reflects on various possibilities of γH2AX/53BP1 foci elimination. Detail
curves of elimination kinetics show that efficiency and kinetics of the DSB repair generally decreases with the increasing LET value. We prove that LET parameter can be suitable for the estimation of the DNA damage degree, but it does not consider spatial distribution of ionizations that is given mainly by ion energy and ion charge. This case includes low-energy radiation mediated by boron or neon ions that despite of comparable LET values, induce formation of different repairable DSBs. Slower and less efficient γH2AX/53BP1 foci elimination has been observed in the cells inducted by neon ions with slightly higher energy. Subsequent micro-morphological analyzes also revealed significant differences in
the complexity as well as in morphology of these foci. Higher efficiency of neon ions is attributed to a more dense spatial distribution of ionizations in micro-surrounding of particle track that was based on calculations and simulations wider for neon ions. In accordance with the efficient DSB repair, the cells underwent apoptosis after γ-rays in a much lower proportion in comparison with the high-LET radiation. In case of different types of radiation with high-LET values, induction of apoptosis does not correlate with increasing LET and damage complexity, but rather with an average number of particles passed through the cell core.

Cite article as:
L. Ježková , "DNA damage and repair after exposure to ionizing radiation with different linear energy transfer", Dissertation thesis at the UCT in Prague (2018)