Testing of a human blood gene signature for quantitative dose reconstruction of radiation dose: dose rate effects
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE224878 | GEO | 2026/02/26
REPOSITORIES: GEO
Similar Datasets
Project description:Testing of a human blood gene signature for quantitative dose reconstruction of radiation dose: dose rate effects
| PRJNA932841 | ENA
Project description:Background: The effects of dose-rate and its implications on radiation biodosimetry methods are not well studied in the context of large-scale radiological scenarios. There are significant health risks to individuals exposed to an acute dose in such an event, but the most realistic scenario would be a combination of exposure to both high and low dose-rates, from both external and internal radioactivity. It is important therefore, to understand the biological response to prolonged exposure; and further, discover biomarkers that can be used to estimate the extent of damage from low-dose rate exposure and propose appropriate clinical treatment. Methods: We irradiated human whole blood ex vivo to three doses, 0.56 Gy, 2.25 Gy and 4.45 Gy, using two dose rates: 1.1Gy/min and 3.1mGy/min. After 24 hours, we isolated RNA from blood cells and hybridized these to Agilent Whole Human genome microarrays. We validated the microarray results using qRT-PCR. Results: Microarray results showed that there were 454 significantly differentially expressed genes after prolonged exposure to all doses. After acute exposure, 598 genes were differentially expressed to all doses combined. Gene ontology terms enriched in both sets of genes were related to immune processes and B cell mediated immunity. Genes responding to acute exposure was also enriched in functions related to natural killer cell activation and cell-to-cell signaling. As expected, p53 pathway was found to be significantly enriched at all doses and by both dose-rates of radiation. Prediction algorithms were able to distinguish between low dose-rate and acute exposures, on the basis of a group of genes. These maybe candidates for preliminary testing as markers for differences in gene expression based on dose-rate. Radiation induced gene expression was measured in ex vivo irradiated human blood, at the 24hr time point after irradiation. Doses (0.56 Gy, 2.2 Gy and 4.45 Gy) were delivered by two dose rates, acute dose rate of 1Gy/min and low dose rate of 3.1 mGy/min.
2015-04-28 | E-GEOD-65292 | biostudies-arrayexpress
Project description:Background: The effects of dose-rate and its implications on radiation biodosimetry methods are not well studied in the context of large-scale radiological scenarios. There are significant health risks to individuals exposed to an acute dose in such an event, but the most realistic scenario would be a combination of exposure to both high and low dose-rates, from both external and internal radioactivity. It is important therefore, to understand the biological response to prolonged exposure; and further, discover biomarkers that can be used to estimate the extent of damage from low-dose rate exposure and propose appropriate clinical treatment. Methods: We irradiated human whole blood ex vivo to three doses, 0.56 Gy, 2.25 Gy and 4.45 Gy, using two dose rates: 1.1Gy/min and 3.1mGy/min. After 24 hours, we isolated RNA from blood cells and hybridized these to Agilent Whole Human genome microarrays. We validated the microarray results using qRT-PCR. Results: Microarray results showed that there were 454 significantly differentially expressed genes after prolonged exposure to all doses. After acute exposure, 598 genes were differentially expressed to all doses combined. Gene ontology terms enriched in both sets of genes were related to immune processes and B cell mediated immunity. Genes responding to acute exposure was also enriched in functions related to natural killer cell activation and cell-to-cell signaling. As expected, p53 pathway was found to be significantly enriched at all doses and by both dose-rates of radiation. Prediction algorithms were able to distinguish between low dose-rate and acute exposures, on the basis of a group of genes. These maybe candidates for preliminary testing as markers for differences in gene expression based on dose-rate.
2015-04-28 | GSE65292 | GEO
Project description:Expression profiles in mouse liver exposed to long-term gamma-irradiation were examined to assess in vivo effects of low dose-rate radiation. Three groups of male C57BL/6J mice were exposed to whole body irradiation at dose-rates of 17-20 mGy/day, 0.86-1.0 mGy/day or 0.042-0.050 mGy/day for 401-485 days (cumulative doses were approximately 8 Gy, 0.4 Gy or 0.02 Gy, respectively). Expression profiles were produced for RNA isolated from irradiated individual animals and for pooled RNA from sham-irradiated 3 animals for control. The expression levels of 6 irradiated animals for each dose were compared individually with those of 2 pooled controls (3 irradiated samples to one pooled control in first and second experiments).
2011-01-01 | GSE20562 | GEO
Project description:Radiation therapy, one of the most effective therapies to treat cancer, is highly toxic to healthy tissue. The delivery of radiation at ultra-high dose rates, FLASH radiation therapy (FLASH), has been shown to maintain therapeutic anti-tumor efficacy while sparing normal tissues compared to conventional dose rate irradiation (CONV). Though promising, these studies have been limited mainly to murine models. Here, we leveraged enteroids, three-dimensional cell clusters that mimic the intestine, to study human-specific tissue response to radiation. We observed enteroids have a greater colony growth potential following FLASH compared with CONV. In addition, the enteroids that reformed following FLASH more frequently exhibited proper intestinal polarity. While we did not observe differences in enteroid damage across groups, we did see distinct transcriptomic changes. Specifically, the FLASH enteroids upregulated the expression of genes associated with the WNT-family, cell-cell adhesion, and hypoxia response. These studies validate human enteroids as a model to investigate FLASH and provide further evidence supporting clinical study of this therapy. Insight Box Promising work has been done to demonstrate the potential of ultra-high dose rate radiation (FLASH) to ablate cancerous tissue, while preserving healthy tissue. While encouraging, these findings have been primarily observed using pre-clinical murine and traditional two-dimensional cell culture. This study validates the use of human enteroids as a tool to investigate human-specific tissue response to FLASH. Specifically, the work described demonstrates the ability of enteroids to recapitulate previous in vivo findings, while also providing a lens through which to probe cellular and molecular-level responses to FLASH. The human enteroids described herein offer a powerful model that can be used to probe the underlying mechanisms of FLASH in future studies.
2024-09-16 | GSE275276 | GEO
Project description:Expression profiles in mouse liver exposed to long-term gamma-irradiation were examined to assess in vivo effects of low dose-rate radiation. Three groups of male C57BL/6J mice were exposed to whole body irradiation at dose-rates of 17-20 mGy/day, 0.86-1.0 mGy/day or 0.042-0.050 mGy/day for 401-485 days (cumulative doses were approximately 8 Gy, 0.4 Gy or 0.02 Gy, respectively). Expression profiles were produced for RNA isolated from irradiated individual animals and for pooled RNA from sham-irradiated 3 animals for control. The expression levels of 6 irradiated animals for each dose were compared individually with those of 2 pooled controls (3 irradiated samples to one pooled control in first and second experiments). The experiments were conducted twice at similar dose-rates. In the first experiment, three groups of 8 weeks old male C57BL/6J mice were exposed to whole body irradiation at dose-rates of either 16.6 mGy/day (H1), 0.858 mGy/day (M1) or 0.042 mGy/day (L1) for 485 days (cumulative doses were 8030 mGy, 416 mGy or 20.6 mGy, respectively). In the second experiment, the doe-rates were slightly elevated as 20.0 mGy/day (H2), 1.000 mGy/day (M2) or 0.050 mGy/day (L2) for 401 days (doses were 8015 mGy, 401 mGy or 20 mGy, respectively). A group of control unirradiated mice were set for each experiment (C1, C2).
2011-01-01 | E-GEOD-20562 | biostudies-arrayexpress
Project description:The biological effects of radiation below 100 mGy are still unproven. In this study, we observed the effects of low-dose radiation (100 mGy) on gene expression in human coronary artery endothelial cells (HCAECs) and its effect on molecular signaling.
2025-03-08 | GSE261231 | GEO
Project description:By using RNA sequencing (RNA-seq), we analyzed gene expression profiles in the hippocampus to demonstrate the molecular mechanisms of low-dose-rate radiation in mice model of type II diabetes mellitus
2025-12-28 | GSE255433 | GEO
Project description:Radiation therapy (RT) induces pleiotropic effects on the tumor immune microenvironment, but how these changes are modulated by radiation dose-fractionation is not well understood. Our in vivo data murine data suggests that while changes evoked by RT in the tumor immune compartment are largely concordant between radiation regimens, several key immunological processes are differentially regulated by radiation dose-fractionation.
2020-12-01 | GSE162418 | GEO
Project description:Osteoblast is one of the bone marrow cells and not only play a central role in bone turnover, but also play a role as supporting cell for hematopoietic stem/progenitor cells. In the field of radiotherapy, internal radiotherapy using radioactive isotopes that emit alpha particles is performed, and antitumor effect is expected by radioisotopes (such as 223-Ra) when the primary cancer cells metastasize to bone marrow. In general, higher dose rates of ionising radiation can induce cell death through DNA damage. However, the extent of DNA damage and repair (radiosensitivity) varies between tissue cell types. In the bone marrow environment, there are many unknowns regarding the radiosensitivity and the its related gene expression in osteoblast, especially the expression status of micro RNAs (miRNAs). The purpose of this study is to reveal the expression pattern of miRNAs in osteoblasts exposed to alpha particle radiation and to identify miRNAs associated with radiosensitivity. Osteoblastic cell line, MC3T3-E1 cell was exposed to 0.223 Gy/min alpha particles (total dose: 0.5 Gy and 1 Gy) and extracted total RNAs after the incubation of 24 h. A significantly up- or down-regulated 21 miRNAs were observed in comparison to non-irradiated control. Using omicsnet data analysis system, we focused on 5 miRNAs (miR-467f, miR-362-3p, miR-5119, miR-292a-5p, miR-466h-3p) and validated them using RT-qPCR. As a result, A higher expression of miR-362-3p after exposure of alpha particle irradiation was reproducibly observed. These results suggested that osteoblastic cell irradiated to alpha particle radiation has a unique miRNA expression pattern.
2025-02-15 | GSE285946 | GEO