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Variations in the processing of DNA double-strand breaks along 60 MeV therapeutic proton beams.

Chaudhary, P*; Marshall, T I*; Currell, F J*; Kacperek, A*; Schettino, G; Prise, K M* (2016) Variations in the processing of DNA double-strand breaks along 60 MeV therapeutic proton beams. Int. J. Radiat. Oncol. Biol. Phys., 95 (1). pp. 86-94.

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Purpose and Background: Following our previous report on the significant increase in biological effectiveness for clinically modulated 60 MeV proton beams, here we investigated the variations in induction and repair of DNA damage along the proton path(1) Although proton beams are characterized by modest-low Linear Energy Transfer (LET) values, a significant increase in DNA lesion complexity might be expected towards the end of the path. Knowledge of the variation of the DNA repair processes is critical for optimization of proton therapy especially when used in combination with agents impacting the DNA repair.
Method and Materials: Human skin fibroblasts (AG01522) cells were irradiated along a mono-energetic (pristine) and a modulated (Spread Out Bragg Peak, SOBP) proton beam used for treating ocular melanoma at the Douglas Cyclotron, Clatterbridge Centre for Oncology, Wirral, UK. DNA damage response was studied using the 53BP1 foci formation assay. The LET dependence was studied by irradiating the cells at depths corresponding to entrance, proximal, middle and distal positions of SOBP and entrance, peak position for the pristine beam. Sub-population radiosensitivity was analysed through number of foci per cell distribution in the irradiated and the medium sharing bystander cells.
Results: A significant amount of persistent foci was observed at the distal end of SOBP suggesting complex residual DNA damage occurring in correspondence to the highest LET values achievable by modulated proton beams. Medium sharing bystander cells did not reveal any significant increase in foci induction.
Conclusions: Induction and repair of the DNA damage caused along the proton beam path appear to be similar to those caused by X-rays confirming the low LET quality of the proton exposure. This, however, is not the case for the positions at the far end of the beam path where data suggest an increased complexity of the DNA lesions and slow repair kinetics. The lack of significant induction of 53BP1 foci in the medium sharing bystander cells suggests a minor role of cell signalling for DNA damage under these conditions.

Item Type: Article
Keywords: proton therapy, DNA damage, bystander effect
Subjects: Ionising Radiation
Ionising Radiation > Dosimetry
Identification number/DOI: 10.1016/j.ijrobp.2015.07.2279
Last Modified: 02 Feb 2018 13:13
URI: http://eprintspublications.npl.co.uk/id/eprint/7097

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