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15. Competition effect in DNA damage response

Author

Greubel, Christoph, Hable, Volker, Drexler, Guido A., Hauptner, Andreas, Dietzel, Steffen, Strickfaden, Hilmar, Baur, Iris, Krücken, Reiner, Cremer, Thomas, Dollinger, Günther, and Friedl, Anna A.

Published
2008
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16. Proton pencil minibeam irradiation of an in-vivo mouse ear model spares healthy tissue dependent on beam size

Author

Sammer, Matthias, primary, Zahnbrecher, Esther, additional, Dobiasch, Sophie, additional, Girst, Stefanie, additional, Greubel, Christoph, additional, Ilicic, Katarina, additional, Reindl, Judith, additional, Schwarz, Benjamin, additional, Siebenwirth, Christian, additional, Walsh, Dietrich W. M., additional, Combs, Stephanie E., additional, Dollinger, Günther, additional, and Schmid, Thomas E., additional

Published
2019
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17. DNA damage interactions on both nanometer and micrometer scale determine overall cellular damage

Author

Ilicic, Katarina, Greubel, Christoph, Girst, Stefanie, Reindl, Judith, Sammer, Matthias, Schwarz, Benjamin, Siebenwirth, Christian, Walsh, Dietrich W. M., Schmid, Thomas E., Scholz, Michael, and Dollinger, Günther

Abstract

Scientific reports 8(1), 16063 (2018). doi:10.1038/s41598-018-34323-9, Published by Macmillan Publishers Limited, part of Springer Nature, [London]

Published
2018
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18. Beam size limit for pencil minibeam radiotherapy determined from side effects in an in-vivo mouse ear model

Author

Sammer, Matthias, primary, Teiluf, Katharina, additional, Girst, Stefanie, additional, Greubel, Christoph, additional, Reindl, Judith, additional, Ilicic, Katarina, additional, Walsh, Dietrich W. M., additional, Aichler, Michaela, additional, Walch, Axel, additional, Combs, Stephanie E., additional, Wilkens, Jan J., additional, Dollinger, Günther, additional, and Schmid, Thomas E., additional

Published
2019
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19. Local inhibition of rRNA transcription without nucleolar segregation after targeted ion irradiation of the nucleolus

Author

Siebenwirth, Christian, primary, Greubel, Christoph, additional, Drexler, Guido A., additional, Reindl, Judith, additional, Walsh, Dietrich W. M., additional, Schwarz, Benjamin, additional, Sammer, Matthias, additional, Baur, Iris, additional, Pospiech, Helmut, additional, Schmid, Thomas E., additional, Dollinger, Günther, additional, and Friedl, Anna A., additional

Published
2019
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20. Survival of tumor cells after proton irradiation with ultra-high dose rates

Author

Belka Claus, Schmid Thomas E, Drexler Guido A, Greubel Christoph, Hable Volker, Auer Susanne, Dollinger Günther, and Friedl Anna A

Subjects
laser acceleration, proton therapy, dose rate effects, Medical physics. Medical radiology. Nuclear medicine, R895-920, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Laser acceleration of protons and heavy ions may in the future be used in radiation therapy. Laser-driven particle beams are pulsed and ultra high dose rates of >109 Gy s-1may be achieved. Here we compare the radiobiological effects of pulsed and continuous proton beams. Methods The ion microbeam SNAKE at the Munich tandem accelerator was used to directly compare a pulsed and a continuous 20 MeV proton beam, which delivered a dose of 3 Gy to a HeLa cell monolayer within < 1 ns or 100 ms, respectively. Investigated endpoints were G2 phase cell cycle arrest, apoptosis, and colony formation. Results At 10 h after pulsed irradiation, the fraction of G2 cells was significantly lower than after irradiation with the continuous beam, while all other endpoints including colony formation were not significantly different. We determined the relative biological effectiveness (RBE) for pulsed and continuous proton beams relative to x-irradiation as 0.91 ± 0.26 and 0.86 ± 0.33 (mean and SD), respectively. Conclusions At the dose rates investigated here, which are expected to correspond to those in radiation therapy using laser-driven particles, the RBE of the pulsed and the (conventional) continuous irradiation mode do not differ significantly.

Published
2011
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21. DNA damage interactions on both nanometer and micrometer scale determine overall cellular damage

Author

Friedrich, Thomas, primary, Ilicic, Katarina, additional, Greubel, Christoph, additional, Girst, Stefanie, additional, Reindl, Judith, additional, Sammer, Matthias, additional, Schwarz, Benjamin, additional, Siebenwirth, Christian, additional, Walsh, Dietrich W. M., additional, Schmid, Thomas E., additional, Scholz, Michael, additional, and Dollinger, Günther, additional

Published
2018
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22. Live cell imaging of mitochondria following targeted irradiation in situ reveals rapid and highly localized loss of membrane potential

Author

Walsh, Dietrich W. M., primary, Siebenwirth, Christian, additional, Greubel, Christoph, additional, Ilicic, Katarina, additional, Reindl, Judith, additional, Girst, Stefanie, additional, Muggiolu, Giovanna, additional, Simon, Marina, additional, Barberet, Philippe, additional, Seznec, Hervé, additional, Zischka, Hans, additional, Multhoff, Gabriele, additional, Schmid, Thomas E., additional, and Dollinger, Guenther, additional

Published
2017
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24. Session 23: Radiation therapy III – Particle therapy II

Author

Dollinger, Günther, primary, Greubel, Christoph, additional, Reindl, Judith, additional, Girst, Stephanie, additional, Schwarz, Benjamin, additional, Siebenwirth, Christian, additional, Walsh, Dieter, additional, Ilicic, Katarina, additional, Multhoff, Gabriele, additional, Wilkens, Jan, additional, and Schmid, Thomas E., additional

Published
2017
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25. Live cell imaging at the Munich ion microbeam SNAKE – a status report

Author

Drexler, Guido A, Siebenwirth, Christian, Drexler, Sophie E, Girst, Stefanie, Greubel, Christoph, Dollinger, Günther, and Friedl, Anna A

Subjects
Fluorescence microscopy, Ions, Cells, Radiobiology, Review, equipment and supplies, Molecular Imaging, Particles, Live-cell imaging, Oncology, Radiology Nuclear Medicine and imaging, Humans, Particle Accelerators, Micro-irradiation
Abstract

Ion microbeams are important tools in radiobiological research. Still, the worldwide number of ion microbeam facilities where biological experiments can be performed is limited. Even fewer facilities combine ion microirradiation with live-cell imaging to allow microscopic observation of cellular response reactions starting very fast after irradiation and continuing for many hours. At SNAKE, the ion microbeam facility at the Munich 14 MV tandem accelerator, a large variety of biological experiments are performed on a regular basis. Here, recent developments and ongoing research projects at the ion microbeam SNAKE are presented with specific emphasis on live-cell imaging experiments. An overview of the technical details of the setup is given, including examples of suitable biological samples. By ion beam focusing to submicrometer beam spot size and single ion detection it is possible to target subcellular structures with defined numbers of ions. Focusing of high numbers of ions to single spots allows studying the influence of high local damage density on recruitment of damage response proteins. Electronic supplementary material The online version of this article (doi:10.1186/s13014-015-0350-7) contains supplementary material, which is available to authorized users.

Published
2015

26. Depletion of Histone Demethylase Jarid1A Resulting in Histone Hyperacetylation and Radiation Sensitivity Does Not Affect DNA Double-Strand Break Repair

Author

Penterling, Corina, primary, Drexler, Guido A., additional, Böhland, Claudia, additional, Stamp, Ramona, additional, Wilke, Christina, additional, Braselmann, Herbert, additional, Caldwell, Randolph B., additional, Reindl, Judith, additional, Girst, Stefanie, additional, Greubel, Christoph, additional, Siebenwirth, Christian, additional, Mansour, Wael Y., additional, Borgmann, Kerstin, additional, Dollinger, Günther, additional, Unger, Kristian, additional, and Friedl, Anna A., additional

Published
2016
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28. A New Nanobody-Based Biosensor to Study Endogenous PARP1 In Vitro and in Live Human Cells

Author

Buchfellner, Andrea, primary, Yurlova, Larisa, additional, Nüske, Stefan, additional, Scholz, Armin M., additional, Bogner, Jacqueline, additional, Ruf, Benjamin, additional, Zolghadr, Kourosh, additional, Drexler, Sophie E., additional, Drexler, Guido A., additional, Girst, Stefanie, additional, Greubel, Christoph, additional, Reindl, Judith, additional, Siebenwirth, Christian, additional, Romer, Tina, additional, Friedl, Anna A., additional, and Rothbauer, Ulrich, additional

Published
2016
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35. Survival of tumor cells after proton irradiation with ultra-high dose rates

Author

Auer, Susanne, Hable, Volker, Greubel, Christoph, Drexler, Guido A, Schmid, Thomas E, Belka, Claus, Dollinger, Günther, and Friedl, Anna A

Subjects
lcsh:Medical physics. Medical radiology. Nuclear medicine, Time Factors, Cell Survival, lcsh:R895-920, Apoptosis, lcsh:RC254-282, laser acceleration, Neoplasms, proton therapy, Humans, Heavy Ions, Ions, Radiotherapy, Research, Lasers, X-Rays, Cell Cycle, dose rate effects, Flow Cytometry, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Microscopy, Fluorescence, Oncology, Radiology Nuclear Medicine and imaging, Particle Accelerators, Protons, Relative Biological Effectiveness, HeLa Cells
Abstract

Background Laser acceleration of protons and heavy ions may in the future be used in radiation therapy. Laser-driven particle beams are pulsed and ultra high dose rates of >109 Gy s-1may be achieved. Here we compare the radiobiological effects of pulsed and continuous proton beams. Methods The ion microbeam SNAKE at the Munich tandem accelerator was used to directly compare a pulsed and a continuous 20 MeV proton beam, which delivered a dose of 3 Gy to a HeLa cell monolayer within < 1 ns or 100 ms, respectively. Investigated endpoints were G2 phase cell cycle arrest, apoptosis, and colony formation. Results At 10 h after pulsed irradiation, the fraction of G2 cells was significantly lower than after irradiation with the continuous beam, while all other endpoints including colony formation were not significantly different. We determined the relative biological effectiveness (RBE) for pulsed and continuous proton beams relative to x-irradiation as 0.91 ± 0.26 and 0.86 ± 0.33 (mean and SD), respectively. Conclusions At the dose rates investigated here, which are expected to correspond to those in radiation therapy using laser-driven particles, the RBE of the pulsed and the (conventional) continuous irradiation mode do not differ significantly.

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36. Superresolution light microscopy shows nanostructure of carbon ion radiation-induced DNA double-strand break repair foci.

Author

Lopez Perez R, Best G, Nicolay NH, Greubel C, Rossberger S, Reindl J, Dollinger G, Weber KJ, Cremer C, and Huber PE

Subjects
Cell Line, Tumor, Gene Expression Regulation, Histones genetics, Histones metabolism, Humans, DNA Breaks, Double-Stranded, DNA Repair physiology, Heavy Ion Radiotherapy, Microscopy methods
Abstract

Carbon ion radiation is a promising new form of radiotherapy for cancer, but the central question about the biologic effects of charged particle radiation is yet incompletely understood. Key to this question is the understanding of the interaction of ions with DNA in the cell's nucleus. Induction and repair of DNA lesions including double-strand breaks (DSBs) are decisive for the cell. Several DSB repair markers have been used to investigate these processes microscopically, but the limited resolution of conventional microscopy is insufficient to provide structural insights. We have applied superresolution microscopy to overcome these limitations and analyze the fine structure of DSB repair foci. We found that the conventionally detected foci of the widely used DSB marker γH2AX (Ø 700-1000 nm) were composed of elongated subfoci with a size of ∼100 nm consisting of even smaller subfocus elements (Ø 40-60 nm). The structural organization of the subfoci suggests that they could represent the local chromatin structure of elementary DSB repair units at the DSB damage sites. Subfocus clusters may indicate induction of densely spaced DSBs, which are thought to be associated with the high biologic effectiveness of carbon ions. Superresolution microscopy might emerge as a powerful tool to improve our knowledge of interactions of ionizing radiation with cells.-Lopez Perez, R., Best, G., Nicolay, N. H., Greubel, C., Rossberger, S., Reindl, J., Dollinger, G., Weber, K.-J., Cremer, C., Huber, P. E. Superresolution light microscopy shows nanostructure of carbon ion radiation-induced DNA double-strand break repair foci., (© FASEB.)

Published
2016
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37. Differences in the kinetics of gamma-H2AX fluorescence decay after exposure to low and high LET radiation.

Author

Schmid TE, Dollinger G, Beisker W, Hable V, Greubel C, Auer S, Mittag A, Tarnok A, Friedl AA, Molls M, and Röper B

Subjects
Carbon, Cell Cycle, DNA Breaks, Double-Stranded, Fluorescent Antibody Technique, HeLa Cells, Humans, Kinetics, Heavy Ions, Histones chemistry, Linear Energy Transfer
Abstract

Purpose: In order to obtain more insight into heavy ion tumour therapy, some features of the underlying molecular mechanisms controlling the cellular response to high linear energy transfer (LET) radiation are currently analysed., Materials and Methods: We analysed the decay of the integrated fluorescence intensity of gamma-H2AX (phosphorylated histone H2AX) which is thought to reflect the repair kinetics of radiation-induced DNA double-strand breaks (DSB) using Laser-Scanning-Cytometry. Asynchronous human HeLa cells were irradiated with a single dose of either 1.89 Gy of 55 MeV carbon ions or 5 Gy of 70 kV X-rays., Results: Measurements of the gamma-H2AX-intensities from 15-60 min resulted in a 16 % decrease for carbon ions and in a 43 % decrease for X-rays. After 21 h, the decrease was 77 % for carbon ions and 85 % for X-rays. The corresponding time-effect relationship was fitted by a bi-exponential function showing a fast and a slow component with identical half-life values for both radiation qualities being 24 +/- 4 min and 13.9 +/- 0.7 h, respectively. Apparent differences in the kinetics following high and low LET irradiation could completely be attributed to quantitative differences in their contributions, with the slow component being responsible for 47 % of the repair after exposure to X-rays as compared to 80 % after carbon ion irradiation., Conclusion: gamma-H2AX loss kinetics follows a bi-exponential decline with two definite decay times independent of LET. The higher contribution of the slow component determined for carbon ion exposure is thought to reflect the increased amount of complex DSB induced by high LET radiation.

Published
2010
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