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Radiation Type- and Dose-Specific Transcriptional Responses across Healthy and Diseased Mammalian Tissues

ORCID
0000-0002-7414-546X
Affiliation
DNA Damage Laboratory, Physics Department, School of Applied Mathematical and Physical Sciences, National Technical University of Athens (NTUA), Zografou, 15780 Athens, Greece
Sagkrioti, Eftychia;
ORCID
0000-0003-1275-0020
Affiliation
Department of Technical Programs, Izmir Vocational School, Dokuz Eylül University, Buca, Izmir 35380, Turkey
Biz, Gökay Mehmet;
ORCID
0000-0002-0269-6625
Affiliation
Izmir Biomedicine and Genome Center (IBG), Balcova, Izmir 35340, Turkey
Takan, Işıl;
Affiliation
Izmir Biomedicine and Genome Center (IBG), Balcova, Izmir 35340, Turkey
Asfa, Seyedehsadaf;
ORCID
0000-0003-4168-7737
Affiliation
DNA Damage Laboratory, Physics Department, School of Applied Mathematical and Physical Sciences, National Technical University of Athens (NTUA), Zografou, 15780 Athens, Greece
Nikitaki, Zacharenia;
Affiliation
DNA Damage Laboratory, Physics Department, School of Applied Mathematical and Physical Sciences, National Technical University of Athens (NTUA), Zografou, 15780 Athens, Greece
Zanni, Vassiliki;
ORCID
0000-0002-2865-0414
Affiliation
Department of Biomedical Engineering, Istanbul Medipol University, Istanbul 34810, Turkey
Kars, Rumeysa Hanife;
ORCID
0000-0002-2223-3580
Affiliation
German Aerospace Center (DLR), Institute of Aerospace Medicine, Radiation Biology, Linder Höhe, D-51147 Köln, Germany
Hellweg, Christine E.;
Affiliation
Canadian Nuclear Laboratories, Chalk River, ON K0J 1J0, Canada
Azzam, Edouard I.;
ORCID
0000-0001-8249-2202
Affiliation
DNA Damage Laboratory, Physics Department, School of Applied Mathematical and Physical Sciences, National Technical University of Athens (NTUA), Zografou, 15780 Athens, Greece
Logotheti, Stella;
Affiliation
Izmir Biomedicine and Genome Center (IBG), Balcova, Izmir 35340, Turkey
Pavlopoulou, Athanasia;
ORCID
0000-0002-5971-0010
Affiliation
DNA Damage Laboratory, Physics Department, School of Applied Mathematical and Physical Sciences, National Technical University of Athens (NTUA), Zografou, 15780 Athens, Greece
Georgakilas, Alexandros G.

Ionizing radiation (IR) is a genuine genotoxic agent and a major modality in cancer treatment. IR disrupts DNA sequences and exerts mutagenic and/or cytotoxic properties that not only alter critical cellular functions but also impact tissues proximal and distal to the irradiated site. Unveiling the molecular events governing the diverse effects of IR at the cellular and organismal levels is relevant for both radiotherapy and radiation protection. Herein, we address changes in the expression of mammalian genes induced after the exposure of a wide range of tissues to various radiation types with distinct biophysical characteristics. First, we constructed a publicly available database, termed RadBioBase, which will be updated at regular intervals. RadBioBase includes comprehensive transcriptomes of mammalian cells across healthy and diseased tissues that respond to a range of radiation types and doses. Pertinent information was derived from a hybrid analysis based on stringent literature mining and transcriptomic studies. An integrative bioinformatics methodology, including functional enrichment analysis and machine learning techniques, was employed to unveil the characteristic biological pathways related to specific radiation types and their association with various diseases. We found that the effects of high linear energy transfer (LET) radiation on cell transcriptomes significantly differ from those caused by low LET and are consistent with immunomodulation, inflammation, oxidative stress responses and cell death. The transcriptome changes also depend on the dose since low doses up to 0.5 Gy are related with cytokine cascades, while higher doses with ROS metabolism. We additionally identified distinct gene signatures for different types of radiation. Overall, our data suggest that different radiation types and doses can trigger distinct trajectories of cell-intrinsic and cell-extrinsic pathways that hold promise to be manipulated toward improving radiotherapy efficiency and reducing systemic radiotoxicities.

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