期刊
CANCERS
卷 14, 期 6, 页码 -出版社
MDPI
DOI: 10.3390/cancers14061545
关键词
53BP1; cell death; DNA damage; epidermis; gamma-H2AX; proton minibeam radiation therapy; DNA repair; skin model
类别
资金
- EU transnational access program RADIATE
Proton minibeam radiotherapy (pMBRT) can achieve tissue-sparing effects at the sub-cellular level, reducing side effects to the skin, and successfully repairing DNA damage.
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 mu m, 408 mu m and 920 mu m 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. gamma-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 mu m pMBRT induced sharply localized severe DNA damage (pan-gamma-H2AX) in cells at the dose peaks, while damage in the dose valleys was similar to sham control. pMBRT with 408 mu m and 920 mu m 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-gamma-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.
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