Planar Proton Minibeam Irradiation Elicits Spatially Confined DNA Damage in a Human Epidermis Model

Cancers

Sarah Rudigkeit¹  Matthias Sammer¹  Jan Grundhöfer¹  Nicole Matejka¹  Judith Reindl¹  Jessica Müller²  Steffen Müller²  Stephanie-Quinta Wagner²  Matthias Port²  Harry Scherthan²  Sarah Schoof² 

[1] Angewandte Physik und Messtechnik, Universität der Bundeswehr München, Werner-Heisenberg-Weg 39, 85577 Neubiberg, Germany;Institut für Radiobiologie der Bundeswehr in Verb. mit der Universität Ulm, Neuherbergstr. 11, 80937 München, Germany;

关键词: 53BP1;    cell death;    DNA damage;    epidermis;    γ-H2AX;    proton minibeam radiation therapy;   

DOI  :  10.3390/cancers14061545

来源: DOAJ

【 摘 要 】

Purpose: High doses of ionizing radiation in radiotherapy can elicit undesirable side effects to the skin. Proton minibeam radiotherapy (pMBRT) may circumvent such limitations due to tissue-sparing effects observed at the macro scale. Here, we mapped DNA damage dynamics in a 3D tissue context at the sub-cellular level. Methods: Epidermis models were irradiated with planar proton minibeams of 66 µm, 408 µm and 920 µm widths and inter-beam-distances of 2.5 mm at an average dose of 2 Gy using the scanning-ion-microscope SNAKE in Garching, GER. γ-H2AX + 53BP1 and cleaved-caspase-3 immunostaining revealed dsDNA damage and cell death, respectively, in time courses from 0.5 to 72 h after irradiation. Results: Focused 66 µm pMBRT induced sharply localized severe DNA damage (pan-γ-H2AX) in cells at the dose peaks, while damage in the dose valleys was similar to sham control. pMBRT with 408 µm and 920 µm minibeams induced DSB foci in all cells. At 72 h after irradiation, DNA damage had reached sham levels, indicating successful DNA repair. Increased frequencies of active-caspase-3 and pan-γ-H2AX-positive cells revealed incipient cell death at late time points. Conclusions: The spatially confined distribution of DNA damage appears to underlie the tissue-sparing effect after focused pMBRT. Thus, pMBRT may be the method of choice in radiotherapy to reduce side effects to the skin.

【 授权许可】

Unknown