Ars moriendi: Proteases as sculptors of cellular suicide

Heib, Michelle; Weiß, Jonas; Saggau, Carina; Hoyer, Justus; Chico, Johaiber Fuchslocher; Voigt, Susann; Adam, Dieter

doi:10.1016/j.bbamcr.2021.119191

Cited by 2 publications

(1 citation statement)

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“…Previous analyses have shown that minibeam irradiations with X-rays or protons lead to higher cell viabilities relative to wide-field irradiation, as assayed by the MTT assay [28]. To further investigate whether focused pMBRT is associated with cell killing and to determine whether late-appearing pan-γ-H2AX-positive cell nuclei mark cells that undergo cell death, we investigated the spatial and temporal occurrence of cells expressing pan-γ-H2AX and dying cells expressing the activated form of the executioner caspase 3 [36] (act. cas 3) in the epidermis models (Figure 8A).…”

Section: Cell Death After Proton Minibeam Irradiationmentioning

confidence: 99%

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

Scherthan

Wagner

Grundhöfer

et al. 2022

Cancers

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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.

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Section: Cell Death After Proton Minibeam Irradiationmentioning

confidence: 99%