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Changing the gravity vector direction by inverted culture enhances radiation-induced cell damage.

ABSTRACT: In recent years, it has become clear that the cytotoxicity of γ-irradiation of cells is increased under microgravity conditions. However, there has been no study of the effect of the gravity vector direction, rather than the magnitude, on γ-ray-induced cytotoxicity. Therefore, in this study, we inverted cultures of human bronchial epithelium BEAS-2B cells and human lung cancer A549 cells in order to change the gravity vector direction by 180° with respect to the cells and observed the cellular response to radiation in this state. We found that cells in inverted culture showed increased irradiation-induced production of reactive oxygen species and decreased expression of the antioxidant protein thioredoxin-1 compared to cells in normal culture. Furthermore, the DNA damage response was delayed in γ-irradiated cells in inverted culture, and the number of unrepaired DNA sites was increased, compared to irradiated cells in normal culture. γ-Ray-induced cell death and the number of G₂-M arrested cells were increased in inverted culture, in accordance with the decreased capacity for DNA repair. Our findings suggest that the gravity vector direction, as well as its magnitude, alters the cellular response to radiation.

SUBMITTER: Mizoguchi Y

PROVIDER: S-EPMC11325285 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature

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Changing the gravity vector direction by inverted culture enhances radiation-induced cell damage.

Mizoguchi Yuma Y Kamimura Masao M Kitabatake Kazuki K Uchiumi Fumiaki F Aoki Shin S Tsukimoto Mitsutoshi M

Biochemistry and biophysics reports 20240722

In recent years, it has become clear that the cytotoxicity of γ-irradiation of cells is increased under microgravity conditions. However, there has been no study of the effect of the gravity vector direction, rather than the magnitude, on γ-ray-induced cytotoxicity. Therefore, in this study, we inverted cultures of human bronchial epithelium BEAS-2B cells and human lung cancer A549 cells in order to change the gravity vector direction by 180° with respect to the cells and observed the cellular r ...[more]

PMID: 39149414

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Project description:Radiation induced bystander effects are an important component of the overall response of cells to irradiation and are associated with human health risks. The mechanism responsible includes intra-cellular and inter-cellular signaling by which the bystander response is propagated. However, details of the signaling mechanism are not well defined.We measured the bystander response of Mrad9+/+ and Mrad9-/- mouse embryonic stem cells, as well as human H1299 cells with inherent or RNA interference-mediated reduced RAD9 levels after exposure to 1 Gy ? particles, by scoring chromosomal aberrations and micronuclei formation, respectively. In addition, we used microarray gene expression analyses to profile the transcriptome of directly irradiated and bystander H1299 cells.We demonstrated that Mrad9 null enhances chromatid aberration frequency induced by radiation in bystander mouse embryonic stem cells. In addition, we found that H1299 cells with reduced RAD9 protein levels showed a higher frequency of radiation induced bystander micronuclei formation, compared with parental cells containing inherent levels of RAD9. The enhanced bystander response in human cells was associated with a unique transcriptomic profile. In unirradiated cells, RAD9 reduction broadly affected stress response pathways at the mRNA level; there was reduction in transcript levels corresponding to genes encoding multiple members of the UVA-MAPK and p38MAPK families, such as STAT1 and PARP1, suggesting that these signaling mechanisms may not function optimally when RAD9 is reduced. Using network analysis, we found that differential activation of the SP1 and NUPR1 transcriptional regulators was predicted in directly irradiated and bystander H1299 cells. Transcription factor prediction analysis also implied that HIF1? (Hypoxia induced factor 1 alpha) activation by protein stabilization in irradiated cells could be a negative predictor of the bystander response, suggesting that local hypoxic stress experienced by cells directly exposed to radiation may influence whether or not they will elicit a bystander response in neighboring cells.

Dataset Information

Changing the gravity vector direction by inverted culture enhances radiation-induced cell damage.

Publications

Changing the gravity vector direction by inverted culture enhances radiation-induced cell damage.

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