Expression Profile of Cell Cycle-Related Genes in Human Fibroblasts Exposed Simultaneously to Radiation and Simulated Microgravity

Ikeda, Hiroko; Muratani, Masafumi; Hidema, Jun; Hada, Megumi; Fujiwara, Keigi; Souda, Hikaru; Yoshida, Yukari; Takahashi, Akio

doi:10.3390/ijms20194791

Cited by 27 publications

(28 citation statements)

References 75 publications

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“…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]. HZE particles themselves induce complex DNA damage and arrest DNA repair process, and also failure to arrest at the G1/S, G2 checkpoints under microgravity; the combination of these responses will lead to genomic instability, including chromosome aberrations, and eventually lead to malignant transformation of those cells.…”

Section: Discussionsupporting

confidence: 66%

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: 66%

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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“…We found that the expression of cell cycle-suppressing genes decreased, and that of cell cycle-promoting genes increased after C-ion irradiation under µG compared with irradiation [19]. The cell cycle may pass through the checkpoints with DNA damage due to the combined effects of C-ion and µG, suggesting that increased genomic instability might occur in space [19]. Indeed, we also found an increased frequency of chromosome aberrations (CA) in cells exposed to both radiation and µG, compared to those treated by radiation only [20].…”

Section: Introductionmentioning

confidence: 80%

“…Using these experimental set-ups, we have earlier studied the combined effects of radiation and µG on human fibroblasts, which are adherent cells. We found that the expression of cell cycle-suppressing genes decreased, and that of cell cycle-promoting genes increased after C-ion irradiation under µG compared with irradiation [19]. The cell cycle may pass through the checkpoints with DNA damage due to the combined effects of C-ion and µG, suggesting that increased genomic instability might occur in space [19].…”

Section: Introductionmentioning

confidence: 84%

“…For this reason, it is important to investigate the effects of both low-and high-LET exposure under the µG. In our previous studies, we have shown changes in cell cycle-related genes expression [19] and increased frequency of CA [20] in human fibroblasts using our unique SSS [17,18].…”

Section: Discussionmentioning

confidence: 99%

“…In our previous study, we found decreased cell cycle-suppressing gene and increased cell cycle-promoting genes on human fibroblasts grown under µG and C-ion irradiation. It was suggested that cells containing DNA damages induced by the combined stimulation with µG and C-ion may be allowed to rapidly pass through the cell cycle checkpoints without complete DNA repair, and that this may induce increased CA in these cells [19]. Further studies are needed to test this hypothesis.…”

Section: Discussionmentioning

confidence: 99%

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

Yamanouchi

Rhone

Mao

et al. 2020

Life

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During space travel, humans are continuously exposed to two major environmental stresses, microgravity (μG) and space radiation. One of the fundamental questions is whether the two stressors are interactive. For over half a century, many studies were carried out in space, as well as using devices that simulated μG on the ground to investigate gravity effects on cells and organisms, and we have gained insights into how living organisms respond to μG. However, our knowledge on how to assess and manage human health risks in long-term mission to the Moon or Mars is drastically limited. For example, little information is available on how cells respond to simultaneous exposure to space radiation and μG. In this study, we analyzed the frequencies of chromosome aberrations (CA) in cultured human lymphoblastic TK6 cells exposed to X-ray or carbon ion under the simulated μG conditions. A higher frequency of both simple and complex types of CA were observed in cells exposed to radiation and μG simultaneously compared to CA frequency in cells exposed to radiation only. Our study shows that the dose response data on space radiation obtained at the 1G condition could lead to the underestimation of astronauts’ potential risk for health deterioration, including cancer. This study also emphasizes the importance of obtaining data on the molecular and cellular responses to irradiation under μG conditions.

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Study of Rotary Cell Culture System-Induced Microgravity Effects on Cancer Biomarkers

Singh

2022

Cancer Biomarkers

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Expression Profile of Cell Cycle-Related Genes in Human Fibroblasts Exposed Simultaneously to Radiation and Simulated Microgravity

Cited by 27 publications

References 75 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

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

Study of Rotary Cell Culture System-Induced Microgravity Effects on Cancer Biomarkers

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