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

Eftychia Sagkrioti; Gökay Mehmet Biz; Işıl Takan; Seyedehsadaf Asfa; Zacharenia Nikitaki; Vassiliki Zanni; Rumeysa Hanife Kars; Christine E Hellweg; Edouard I Azzam; Stella Logotheti; Athanasia Pavlopoulou; Alexandros G Georgakilas

doi:10.3390/antiox11112286

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

Antioxidants (Basel). 2022 Nov 18;11(11):2286. doi: 10.3390/antiox11112286.

Authors

Affiliations

¹ DNA Damage Laboratory, Physics Department, School of Applied Mathematical and Physical Sciences, National Technical University of Athens (NTUA), Zografou, 15780 Athens, Greece.
² Biology Department, National and Kapodistrian University of Athens (NKUA), 15784 Athens, Greece.
³ Department of Technical Programs, Izmir Vocational School, Dokuz Eylül University, Buca, Izmir 35380, Turkey.
⁴ Izmir Biomedicine and Genome Center (IBG), Balcova, Izmir 35340, Turkey.
⁵ Izmir International Biomedicine and Genome Institute, Dokuz Eylül University, Balcova, Izmir 35340, Turkey.
⁶ Department of Biomedical Engineering, Istanbul Medipol University, Istanbul 34810, Turkey.
⁷ German Aerospace Center (DLR), Institute of Aerospace Medicine, Radiation Biology, Linder Höhe, D-51147 Köln, Germany.
⁸ Canadian Nuclear Laboratories, Chalk River, ON K0J 1J0, Canada.

Abstract

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.

Keywords: bioinformatics; gene signature; oxidative stress; radiation response; radiobiology database; transcriptomics.

Grants and funding

AGG was funded from the project 21GRD02 BIOSPHERE, which has received funding from the European Partnership on Metrology, co-financed by the European Union’s Horizon Europe Research and Innovation Programme and by the Participating States. Funder ID: 10.13039/100019599. Grant number: 21GRD02 BIOSPHERE.