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A Meta-Analysis of the Effects of High-LET Ionizing Radiations in Human Gene Expression

Michalettou, Theodora-Dafni and Michalopoulos, Ioannis and Costes, Sylvain V. and Hellweg, Christine E. and Hada, Megumi and Georgakilas, Alexandros G. (2021) A Meta-Analysis of the Effects of High-LET Ionizing Radiations in Human Gene Expression. Life, 11 (2), p. 115. Multidisciplinary Digital Publishing Institute (MDPI). doi: 10.3390/life11020115. ISSN 2075-1729.

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Official URL: http://dx.doi.org/10.3390/life11020115

Abstract

The use of high linear energy transfer (LET) ionizing radiation (IR) is progressively being incorporated in radiation therapy due to its precise dose localization and high relative biological effectiveness. At the same time, these benefits of particle radiation become a high risk for astronauts in the case of inevitable cosmic radiation exposure. Nonetheless, DNA Damage Response (DDR) activated via complex DNA damage in healthy tissue, occurring from such types of radiation, may be instrumental in the induction of various chronic and late effects. An approach to elucidating the possible underlying mechanisms is studying alterations in gene expression. To this end, we identified differentially expressed genes (DEGs) in high Z and high energy (HZE) particle-, γ-ray- and X-rayexposed healthy human tissues, utilizing microarray data available in public repositories. Differential gene expression analysis (DGEA) was conducted using the R programming language. Consequently, four separate meta-analyses were conducted, after DEG lists were grouped depending on radiation type, radiation dose and time of collection post-irradiation. To highlight the biological background of each meta-analysis group, functional enrichment analysis and biological network construction were conducted. For HZE particle exposure at 8–24 h post-irradiation, the most interesting finding is the variety of DNA repair mechanisms that were downregulated, a fact that is probably correlated with complex DNA damage formation. Simultaneously, after X-ray exposure during the same hours after irradiation, DNA repair mechanisms continue to take place. Finally, in a further comparison of lowand high-LET radiation effects, the most prominent result is that autophagy mechanisms seem to persist and that adaptive immune induction seems to be present. Such bioinformatics approaches may aid in obtaining an overview of the cellular response to high-LET particles. Understanding these response mechanisms can consequently aid in the development of countermeasures for future space missions and ameliorate heavy ion treatments.

Item URL in elib:https://elib.dlr.de/140921/
Document Type:Article
Title:A Meta-Analysis of the Effects of High-LET Ionizing Radiations in Human Gene Expression
Authors:
AuthorsInstitution or Email of AuthorsAuthor's ORCID iD
Michalettou, Theodora-DafniDNA Damage Laboratory, Physics Department, School of Applied Mathematical and Physical Sciences, National Technical University of Athens and Centre of Systems Biology, Biomedical Research Foundation, Academy of Athens, Greece; daphnelettos (at) biol.uoa.grhttps://orcid.org/0000-0003-2119-1099
Michalopoulos, IoannisCentre of Systems Biology, Biomedical Research Foundation, Academy of Athens, 115 27 Athens, Greece; imichalop (at) bioacademy.grhttps://orcid.org/0000-0001-8991-8712
Costes, Sylvain V.NASA Ames Research Center, Space Biosciences, Moffett Field, CA 94035, USA; sylvain.v.costes (at) nasa.govhttps://orcid.org/0000-0002-8542-2389
Hellweg, Christine E.Radiation Biology Department, Institute of Aerospace Medicine, German Aerospace Center (DLR), Linder Höhe, Cologne, Germany; Christine.Hellweg (at) dlr.dehttps://orcid.org/0000-0002-2223-3580
Hada, MegumiRadiation Institute for Science & Engineering, Prairie View A&M University, Prairie View, TX 77446, USA; mehada (at) pvamu.eduhttps://orcid.org/0000-0002-8523-9111
Georgakilas, Alexandros G.DNA Damage Laboratory, Physics Department, School of Applied Mathematical and Physical Sciences, National Technical University of Athens, 157 80 Athens, Greece;alexg (at) mail.ntua.grhttps://orcid.org/0000-0002-5971-0010
Date:3 February 2021
Journal or Publication Title:Life
Refereed publication:Yes
Open Access:Yes
Gold Open Access:Yes
In SCOPUS:Yes
In ISI Web of Science:Yes
Volume:11
DOI :10.3390/life11020115
Page Range:p. 115
Publisher:Multidisciplinary Digital Publishing Institute (MDPI)
ISSN:2075-1729
Status:Published
Keywords:microarrays; high-LET; space radiation; differential gene expression; meta-analysis; computational radiobiology; DNA damage response; functional enrichment analysis
HGF - Research field:Aeronautics, Space and Transport
HGF - Program:Space
HGF - Program Themes:Research under Space Conditions
DLR - Research area:Raumfahrt
DLR - Program:R FR - Research under Space Conditions
DLR - Research theme (Project):R - Project ISS LIFE 2.0
Location: Köln-Porz
Institutes and Institutions:Institute of Aerospace Medicine > Radiation Biology
Deposited By: Kopp, Kerstin
Deposited On:18 Feb 2021 15:55
Last Modified:14 Apr 2021 14:30

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