Abstract
PurposeTo investigate the variations in induction and repair of DNA damage along the proton path, after a previous report on the increasing biological effectiveness along clinically modulated 60-MeV proton beams.Methods and MaterialsHuman skin fibroblast (AG01522) cells were irradiated along a monoenergetic and a modulated spread-out Bragg peak (SOBP) proton beam used for treating ocular melanoma at the Douglas Cyclotron, Clatterbridge Centre for Oncology, Wirral, Liverpool, United Kingdom. The DNA damage response was studied using the 53BP1 foci formation assay. The linear energy transfer (LET) dependence was studied by irradiating the cells at depths corresponding to entrance, proximal, middle, and distal positions of SOBP and the entrance and peak position for the pristine beam.ResultsA significant amount of persistent foci was observed at the distal end of the SOBP, suggesting complex residual DNA double-strand break damage induction corresponding to the highest LET values achievable by modulated proton beams. Unlike the directly irradiated, medium-sharing bystander cells did not show any significant increase in residual foci.ConclusionsThe DNA damage response along the proton beam path was similar to the response of X rays, confirming the low-LET quality of the proton exposure. However, at the distal end of SOBP our data indicate an increased complexity of DNA lesions and slower repair kinetics. A lack of significant induction of 53BP1 foci in the bystander cells suggests a minor role of cell signaling for DNA damage under these conditions.
Highlights
Radiation therapy relies on induction of critical levels of DNA damage in the tumor cells, leading to apoptosis, necrosis, and mitotic cell death [1]
The DNA damage response along the proton beam path was similar to the response of X rays, confirming the low-linear energy transfer (LET) quality of the proton exposure
Most DNA damage induced by low-LET radiation can be efficiently repaired, high-LET radiations are associated with increased formation of repair-refractory clustered DNA lesions, misrepaired double-strand breaks (DSBs), and exchange-type chromosomal aberrations, leading to increased cellular lethality [10]
Summary
Radiation therapy relies on induction of critical levels of DNA damage in the tumor cells, leading to apoptosis, necrosis, and mitotic cell death [1]. Recent technological advances make it possible to treat tumors more precisely than before using spatially and temporally modulated beams [2]. Protons, with their superior depthedose deposition properties over photons, might offer an advantage for treatment of tumors near critical organs [3]. Better dose conformation and higher precision than with photon beams are the key advantages of using proton therapy, the quality of the DNA damage induced and its impact on the cell repair efficiency must be considered to optimize the treatments [11]
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