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-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.
Highlights
Human exposure to ionizing radiation can occur via interaction with various sources, such as the radioactivity emitted from naturally unstable atoms, cosmic radiation and other artificial sources
Functional enrichment analysis of up-and downregulated genes resulting from the three meta-analyses produced lists of statistically significant Gene Ontology (GO) biological processes and biological pathways with a selected false discovery rate (FDR) cutoff of 0.01 (Supplementary Materials, Tables S2–S4)
The enriched gene sets exhibit a level of repeatability due to the selection of reference gene sets from multiple databases, as well as the variety of gene sets that indicate the same group of biological processes or pathways
Summary
Human exposure to ionizing radiation can occur via interaction with various sources, such as the radioactivity emitted from naturally unstable atoms, cosmic radiation and other artificial sources. In contrast to this clinical, local application of such types of radiation (mostly energetic carbon ions), astronauts experience chronic whole-body exposure to cosmic radiation during space flights. Such exposure to galactic cosmic radiation (GCR), which is made up of high-energy protons, relativistic helium ions and high-Z (charges greater than 2) and high energy particles (HZE particles) [1], is a major risk factor during long-term space missions. Space radiation exposure for long periods might affect the immune system, which is already weakened by microgravity [4] and this could endanger the health of astronauts and, the success of the mission. There are still large uncertainties regarding effects related to the reproductive system and embryonic/fetal development concerning the safety of being pregnant after or during a long-term interplanetary mission [5]
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