Heavy ions and X-rays in brain tumor treatment : a comparison of their biological effects on tissue slice cultures

  • Background: In this interdisciplinary project, the biological effects of heavy ions are compared to those of X-rays using tissue slice culture preparations from rodents and humans. Advantages of this biological model are the conservation of an organotypic environment and the independency from genetic immortalization strategies used to generate cell lines. Its open access allows easy treatment and observation via live-imaging microscopy. Materials and methods: Rat brains and human brain tumor tissue are cut into 300 micro m thick tissue slices. These slices are cultivated using a membrane-based culture system and kept in an incubator at 37°C until treatment. The slices are treated with X-rays at the radiation facility of the University Hospital in Frankfurt at doses of up to 40 Gy. The heavy ion irradiations were performed at the UNILAC facility at GSI with different ions of 11.4 A MeV and fluences ranging from 0.5–10 x 106 particles/cm². Using 3D-confocal microscopy, cell-death and immune cell activation of the irradiated slices are analyzed. Planning of the irradiation experiments is done with simulation programs developed at GSI and FIAS. Results: After receiving a single application of either X-rays or heavy ions, slices were kept in culture for up to 9d post irradiation. DNA damage was visualized using gamma H2AXstaining. Here, a dose-dependent increase and time-dependent decrease could clearly be observed for the X-ray irradiation. Slices irradiated with heavy ions showed less gamma H2AX-positive cells distributed evenly throughout the slice, even though particles were calculated to penetrate only 90–100 micro m into the slice. Conclusions: Single irradiations of brain tissue, even at high doses of 40 Gy, will result neither in tissue damage visible on a macroscopic level nor necrosis. This is in line with the view that the brain is highly radio-resistant. However, DNA damage can be detected very well in tissue slices using gamma H2AX-immuno staining. Thus, slice cultures are an excellent tool to study radiation-induced damage and repair mechanisms in living tissues.

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Author:Mareike MüllerGND, Felicitas Merz, Marco DuranteORCiDGND, Volker SeifertORCiD, Johannes RiegerGND, Michel Guy André MittelbronnORCiDGND, Patrick Nikolaus HarterORCiDGND, Igor N. MishustinORCiDGND, Igor A. PshenichnovORCiD, Franz RödelORCiDGND, Horst StöckerORCiDGND, Kosta Schopow, Faramarz Dehghani, Gisela Taucher-Scholz, Ingo Bechmann
Parent Title (German):PTCOG 48. Meeting of the Particle Therapy Co-Operative Group. Heidelberg, 28.09.-03.10.2009
Publisher:German Medical Science GMS Publishing House
Place of publication:Düsseldorf
Document Type:Article
Date of Publication (online):2009/10/13
Date of first Publication:2009/09/24
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Contributing Corporation:Particle Therapy Co-Operative Group
Release Date:2009/10/13
Page Number:2
© 2009 Müller et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.
Source:PTCOG 48. Meeting of the Particle Therapy Co-Operative Group. Heidelberg, 28.09.-03.10.2009. Düsseldorf: German Medical Science GMS Publishing House; 2009. Doc09ptcog142 DOI: 10.3205/09ptcog142, URN: urn:nbn:de:0183-09ptcog1420
Institutes:Physik / Physik
Medizin / Medizin
Fachübergreifende Einrichtungen / Zentrum für Arzneimittelforschung, Entwicklung und Sicherheit (ZAFES)
Wissenschaftliche Zentren und koordinierte Programme / Frankfurt Institute for Advanced Studies (FIAS)
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung-Nicht kommerziell-Keine Bearbeitung 3.0