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Lohberger, B; Barna, S; Glänzer, D; Eck, N; Kerschbaum-Gruber, S; Stasny, K; Leithner, A; Georg, D.
Cellular and Molecular Biological Alterations after Photon, Proton, and Carbon Ions Irradiation in Human Chondrosarcoma Cells Linked with High-Quality Physics Data.
Int J Mol Sci. 2022; 23(19): Doi: 10.3390/ijms231911464 [OPEN ACCESS]
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Führende Autor*innen der Med Uni Graz
Lohberger Birgit
Co-Autor*innen der Med Uni Graz
Eck Nicole
Glänzer Dietmar
Leithner Andreas
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Abstract:
Chondrosarcomas are particularly difficult to treat due to their resistance to chemotherapy and radiotherapy. However, particle therapy can enhance local control and patient survival rates. To improve our understanding of the basic cellular radiation response, as a function of dose and linear energy transfer (LET), we developed a novel water phantom-based setup for cell culture experiments and characterized it dosimetrically. In a direct comparison, human chondrosarcoma cell lines were analyzed with regard to their viability, cell proliferation, cell cycle, and DNA repair behavior after irradiation with X-ray, proton, and carbon ions. Our results clearly showed that cell viability and proliferation were inhibited according to the increasing ionization density, i.e., LET, of the irradiation modes. Furthermore, a prominent G2/M arrest was shown. Gene expression profiling proved the upregulation of the senescence genes CDKN1A (p21), CDKN2A (p16NK4a), BMI1, and FOXO4 after particle irradiation. Both proton or C-ion irradiation caused a positive regulation of the repair genes ATM, NBN, ATXR, and XPC, and a highly significant increase in XRCC1/2/3, ERCC1, XPC, and PCNA expression, with C-ions appearing to activate DNA repair mechanisms more effectively. The link between the physical data and the cellular responses is an important contribution to the improvement of the treatment system.
Find related publications in this database (using NLM MeSH Indexing)
Carbon - administration & dosage
Chondrosarcoma - genetics, radiotherapy
Humans - administration & dosage
Physics - administration & dosage
Proliferating Cell Nuclear Antigen - administration & dosage
Protons - administration & dosage
Water - administration & dosage
X-ray Repair Cross Complementing Protein 1 - administration & dosage

Find related publications in this database (Keywords)
chondrosarcoma
proton irradiation
carbon ions
DNA repair
cell cycle
particle therapy
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