Simultaneous Exposure of Cultured Human Lymphoblastic Cells to Simulated Microgravity and Radiation Increases Chromosome Aberrations

Yamanouchi, Sakuya; Rhone, Jordan; Mao, Jian‐Hua; Fujiwara, Keigi; Saganti, Premkumar B.; Takahashi, Akio; Hada, Megumi

doi:10.3390/life10090187

Cited by 17 publications

(25 citation statements)

References 56 publications

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“…Furthermore, this pattern of DNA repair mechanism arrest that is not observed after low-LET exposure might be correlated with complex DNA damage formation. This increase in complex DNA damage in comparison with X-ray exposure has been previously observed [97] and could involve the triggering of chromosomal translocations [98]. Recent reports show downregulation of cell cycle suppressing genes (ABL1 and CDKN1A) and upregulation of cell cycle promoting genes (CCNB1, CCND1, KPNA2, MCM4, MKI67 and STMN1) in cells exposed to HZE particles under microgravity [99].…”

Section: Discussionsupporting

confidence: 64%

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

Michalettou

Michalopoulos

Costes

et al. 2021

Life

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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.

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Section: Discussionsupporting

confidence: 64%

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

Michalettou

Michalopoulos

Costes

et al. 2021

Life

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“…Heavy ion beams with high linear energy transfer (LET) in space radiation are known to cause cluster DNA damage in which multiple DNA damage occurs within 1–2 helix turns of a DNA molecule [ 4 , 5 , 6 , 7 ]. Compared to X-rays or γ-rays, heavy ion beams cause more chromosomal aberrations such as dicentric chromosomes, translocations, and deletion mutations, resulting in significant biological effects [ 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Repair Kinetics of DNA Double Strand Breaks Induced by Simulated Space Radiation

Oizumi

Ohno

Yamabe

et al. 2020

Life

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Radiation is unavoidable in space. Energetic particles in space radiation are reported to induce cluster DNA damage that is difficult to repair. In this study, normal human fibroblasts were irradiated with components of space radiation such as proton, helium, or carbon ion beams. Immunostaining for γ-H2AX and 53BP1 was performed over time to evaluate the kinetics of DNA damage repair. Our data clearly show that the repair kinetics of DNA double strand breaks (DSBs) induced by carbon ion irradiation, which has a high linear energy transfer (LET), are significantly slower than those of proton and helium ion irradiation. Mixed irradiation with carbon ions, followed by helium ions, did not have an additive effect on the DSB repair kinetics. Interestingly, the mean γ-H2AX focus size was shown to increase with LET, suggesting that the delay in repair kinetics was due to damage that is more complex. Further, the 53BP1 focus size also increased in an LET-dependent manner. Repair of DSBs, characterized by large 53BP1 foci, was a slow process within the biphasic kinetics of DSB repair, suggesting non-homologous end joining with error-prone end resection. Our data suggest that the biological effects of space radiation may be significantly influenced by the dose as well as the type of radiation exposure.

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“…The authors hope that this review will be useful for the evaluation and reduction of pregnancy-related risks of the astronauts who have reproductive functions and plan to be involved in future interplanetary missions, expecting that further efforts will be actively made to collect relevant information regarding the combined effects of high-LET space radiation and gravity changes, e.g., [ 111 , 112 , 113 , 114 , 115 , 116 ], and theoretical based on the differences of the RBE values between low-LET and high-LET particles, e.g., [ 117 ], and also those of between low and high dose rates, e.g., [ 118 ].…”

Section: Discussionmentioning

confidence: 99%

Relative Biological Effectiveness of High LET Particles on the Reproductive System and Fetal Development

Wang

Yasuda

2020

Life

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During a space mission, astronauts are inevitably exposed to space radiation, mainly composed of the particles having high values of linear energy transfer (LET), such as protons, helium nuclei, and other heavier ions. Those high-LET particles could induce severer health damages than low-LET particles such as photons and electrons. While it is known that the biological effectiveness of a specified type of radiation depends on the distribution of dose in time, type of the cell, and the biological endpoint in respect, there are still large uncertainties regarding the effects of high-LET particles on the reproductive system, gamete, embryo, and fetal development because of the limitation of relevant data from epidemiological and experimental studies. To safely achieve the planned deep space missions to the moon and Mars that would involve young astronauts having reproductive functions, it is crucial to know exactly the relevant radiological effects, such as infertility of the parent and various diseases of the child, and then to conduct proper countermeasures. Thus, in this review, the authors present currently available information regarding the relative biological effectiveness (RBE) of high-LET particles on the deterministic effects related to the reproductive system and embryonic/fetal development for further discussions about the safety of being pregnant after or during a long-term interplanetary mission.

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Simultaneous Exposure of Cultured Human Lymphoblastic Cells to Simulated Microgravity and Radiation Increases Chromosome Aberrations

Cited by 17 publications

References 56 publications

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

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

Repair Kinetics of DNA Double Strand Breaks Induced by Simulated Space Radiation

Relative Biological Effectiveness of High LET Particles on the Reproductive System and Fetal Development

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