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Article

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

1
DNA Damage Laboratory, Physics Department, School of Applied Mathematical and Physical Sciences, National Technical University of Athens, 157 80 Athens, Greece
2
Centre of Systems Biology, Biomedical Research Foundation, Academy of Athens, 115 27 Athens, Greece
3
NASA Ames Research Center, Space Biosciences, Moffett Field, CA 94035, USA
4
Radiation Biology Department, Institute of Aerospace Medicine, German Aerospace Center (DLR), Linder Hoehe, 51147 Cologne, Germany
5
Radiation Institute for Science & Engineering, Prairie View A&M University, Prairie View, TX 77446, USA
*
Authors to whom correspondence should be addressed.
Academic Editor: Giorgio Russo
Life 2021, 11(2), 115; https://doi.org/10.3390/life11020115
Received: 31 December 2020 / Revised: 31 January 2021 / Accepted: 31 January 2021 / Published: 3 February 2021
(This article belongs to the Special Issue Radiobiology in Space)
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-ray-exposed 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 low- and 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. View Full-Text
Keywords: microarrays; high-LET; space radiation; differential gene expression; meta-analysis; computational radiobiology; DNA damage response; functional enrichment analysis microarrays; high-LET; space radiation; differential gene expression; meta-analysis; computational radiobiology; DNA damage response; functional enrichment analysis
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MDPI and ACS Style

Michalettou, T.-D.; Michalopoulos, I.; Costes, S.V.; Hellweg, C.E.; Hada, M.; Georgakilas, A.G. A Meta-Analysis of the Effects of High-LET Ionizing Radiations in Human Gene Expression. Life 2021, 11, 115. https://doi.org/10.3390/life11020115

AMA Style

Michalettou T-D, Michalopoulos I, Costes SV, Hellweg CE, Hada M, Georgakilas AG. A Meta-Analysis of the Effects of High-LET Ionizing Radiations in Human Gene Expression. Life. 2021; 11(2):115. https://doi.org/10.3390/life11020115

Chicago/Turabian Style

Michalettou, Theodora-Dafni, Ioannis Michalopoulos, Sylvain V. Costes, Christine E. Hellweg, Megumi Hada, and Alexandros G. Georgakilas 2021. "A Meta-Analysis of the Effects of High-LET Ionizing Radiations in Human Gene Expression" Life 11, no. 2: 115. https://doi.org/10.3390/life11020115

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