Cellular and Molecular Biological Alterations after Photon, Proton, and Carbon Ions Irradiation in Human Chondrosarcoma Cells Linked with High-Quality Physics Data
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...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-09-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/19/11464 |
| _version_ | 1797479028490240000 |
|---|---|
| author | Birgit Lohberger Sandra Barna Dietmar Glänzer Nicole Eck Sylvia Kerschbaum-Gruber Katharina Stasny Andreas Leithner Dietmar Georg |
| author_facet | Birgit Lohberger Sandra Barna Dietmar Glänzer Nicole Eck Sylvia Kerschbaum-Gruber Katharina Stasny Andreas Leithner Dietmar Georg |
| author_sort | Birgit Lohberger |
| collection | DOAJ |
| description | 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 G<sub>2</sub>/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. |
| first_indexed | 2024-03-09T21:40:02Z |
| format | Article |
| id | doaj.art-49cd8d052b044a9597a021c4a1143424 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T21:40:02Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-49cd8d052b044a9597a021c4a11434242023-11-23T20:33:40ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-09-0123191146410.3390/ijms231911464Cellular and Molecular Biological Alterations after Photon, Proton, and Carbon Ions Irradiation in Human Chondrosarcoma Cells Linked with High-Quality Physics DataBirgit Lohberger0Sandra Barna1Dietmar Glänzer2Nicole Eck3Sylvia Kerschbaum-Gruber4Katharina Stasny5Andreas Leithner6Dietmar Georg7Department of Orthopaedics and Trauma, Medical University of Graz, 8036 Graz, AustriaDepartment of Radiation Oncology, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Orthopaedics and Trauma, Medical University of Graz, 8036 Graz, AustriaDepartment of Orthopaedics and Trauma, Medical University of Graz, 8036 Graz, AustriaDepartment of Radiation Oncology, Medical University of Vienna, 1090 Vienna, AustriaMedAustron Ion Therapy Center, 2700 Wiener Neustadt, AustriaDepartment of Orthopaedics and Trauma, Medical University of Graz, 8036 Graz, AustriaDepartment of Radiation Oncology, Medical University of Vienna, 1090 Vienna, AustriaChondrosarcomas 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 G<sub>2</sub>/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.https://www.mdpi.com/1422-0067/23/19/11464chondrosarcomaproton irradiationcarbon ionsDNA repaircell cycleparticle therapy |
| spellingShingle | Birgit Lohberger Sandra Barna Dietmar Glänzer Nicole Eck Sylvia Kerschbaum-Gruber Katharina Stasny Andreas Leithner Dietmar Georg Cellular and Molecular Biological Alterations after Photon, Proton, and Carbon Ions Irradiation in Human Chondrosarcoma Cells Linked with High-Quality Physics Data International Journal of Molecular Sciences chondrosarcoma proton irradiation carbon ions DNA repair cell cycle particle therapy |
| title | Cellular and Molecular Biological Alterations after Photon, Proton, and Carbon Ions Irradiation in Human Chondrosarcoma Cells Linked with High-Quality Physics Data |
| title_full | Cellular and Molecular Biological Alterations after Photon, Proton, and Carbon Ions Irradiation in Human Chondrosarcoma Cells Linked with High-Quality Physics Data |
| title_fullStr | Cellular and Molecular Biological Alterations after Photon, Proton, and Carbon Ions Irradiation in Human Chondrosarcoma Cells Linked with High-Quality Physics Data |
| title_full_unstemmed | Cellular and Molecular Biological Alterations after Photon, Proton, and Carbon Ions Irradiation in Human Chondrosarcoma Cells Linked with High-Quality Physics Data |
| title_short | Cellular and Molecular Biological Alterations after Photon, Proton, and Carbon Ions Irradiation in Human Chondrosarcoma Cells Linked with High-Quality Physics Data |
| title_sort | cellular and molecular biological alterations after photon proton and carbon ions irradiation in human chondrosarcoma cells linked with high quality physics data |
| topic | chondrosarcoma proton irradiation carbon ions DNA repair cell cycle particle therapy |
| url | https://www.mdpi.com/1422-0067/23/19/11464 |
| work_keys_str_mv | AT birgitlohberger cellularandmolecularbiologicalalterationsafterphotonprotonandcarbonionsirradiationinhumanchondrosarcomacellslinkedwithhighqualityphysicsdata AT sandrabarna cellularandmolecularbiologicalalterationsafterphotonprotonandcarbonionsirradiationinhumanchondrosarcomacellslinkedwithhighqualityphysicsdata AT dietmarglanzer cellularandmolecularbiologicalalterationsafterphotonprotonandcarbonionsirradiationinhumanchondrosarcomacellslinkedwithhighqualityphysicsdata AT nicoleeck cellularandmolecularbiologicalalterationsafterphotonprotonandcarbonionsirradiationinhumanchondrosarcomacellslinkedwithhighqualityphysicsdata AT sylviakerschbaumgruber cellularandmolecularbiologicalalterationsafterphotonprotonandcarbonionsirradiationinhumanchondrosarcomacellslinkedwithhighqualityphysicsdata AT katharinastasny cellularandmolecularbiologicalalterationsafterphotonprotonandcarbonionsirradiationinhumanchondrosarcomacellslinkedwithhighqualityphysicsdata AT andreasleithner cellularandmolecularbiologicalalterationsafterphotonprotonandcarbonionsirradiationinhumanchondrosarcomacellslinkedwithhighqualityphysicsdata AT dietmargeorg cellularandmolecularbiologicalalterationsafterphotonprotonandcarbonionsirradiationinhumanchondrosarcomacellslinkedwithhighqualityphysicsdata |