Browse
Submit Data
Databases
API
Help

Dataset Information

9 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Vascular Damage in the Aorta of Wild-Type Mice Exposed to Ionizing Radiation: Sparing and Enhancing Effects of Dose Protraction.

ABSTRACT: During medical (therapeutic or diagnostic) procedures or in other settings, the circulatory system receives ionizing radiation at various dose rates. Here, we analyzed prelesional changes in the circulatory system of wild-type mice at six months after starting acute, intermittent, or continuous irradiation with 5 Gy of photons. Independent of irradiation regimens, irradiation had little impact on left ventricular function, heart weight, and kidney weight. In the aorta, a single acute exposure delivered in 10 minutes led to structural disorganizations and detachment of the aortic endothelium, and intima-media thickening. These morphological changes were accompanied by increases in markers for profibrosis (TGF-β1), fibrosis (collagen fibers), proinflammation (TNF-α), and macrophages (F4/80 and CD68), with concurrent decreases in markers for cell adhesion (CD31 and VE-cadherin) and vascular functionality (eNOS) in the aortic endothelium. Compared with acute exposure, the magnitude of such aortic changes was overall greater when the same dose was delivered in 25 fractions spread over 6 weeks, smaller in 100 fractions over 5 months, and much smaller in chronic exposure over 5 months. These findings suggest that dose protraction alters vascular damage in the aorta, but in a way that is not a simple function of dose rate.

SUBMITTER: Hamada N

PROVIDER: S-EPMC8582417 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Temporal Changes in Sparing and Enhancing Dose Protraction Effects of Ionizing Irradiation for Aortic Damage in Wild-Type Mice.

Project description:In medical and occupational settings, ionizing irradiation of the circulatory system occurs at various dose rates. We previously found sparing and enhancing dose protraction effects for aortic changes in wild-type mice at 6 months after starting irradiation with 5 Gy of photons. Here, we further analyzed changes at 12 months after stating irradiation. Irrespective of irradiation regimens, irradiation little affected left ventricular function, heart weight, and kidney weight. Irradiation caused structural disorganizations and intima-media thickening in the aorta, along with concurrent elevations of markers for proinflammation, macrophage, profibrosis, and fibrosis, and reductions in markers for vascular functionality and cell adhesion in the aortic endothelium. These changes were qualitatively similar but quantitatively less at 12 months than at 6 months. The magnitude of such changes at 12 months was not smaller in 25 fractions (Frs) but was smaller in 100 Frs and chronic exposure than acute exposure. The magnitude at 6 and 12 months was greater in 25 Frs, smaller in 100 Frs, and much smaller in chronic exposure than acute exposure. These findings suggest that dose protraction changes aortic damage, in a fashion that depends on post-irradiation time and is not a simple function of dose rate.

| S-EPMC9321929 | biostudies-literature

Ionizing Irradiation Induces Vascular Damage in the Aorta of Wild-Type Mice.

Project description:There has been a recent upsurge of interest in the effects of ionizing radiation exposure on the circulatory system, because a mounting body of epidemiological evidence suggests that irradiation induces cardio- and cerebrovascular disease at a much lower dose and lower dose rate than previously considered. The goal of our project is to determine whether dose protraction alters radiation effects on the circulatory system in a mouse model. To this end, the use of wild-type mice is pivotal albeit without manifestation of vascular diseases, because disease models (e.g., apolipoprotein E-deficient mice) are prone to hormetic responses following protracted exposures. As such, here, we first set out to analyze prelesional changes in the descending thoracic aorta of wild-type mice up to six months after a single acute exposure to 0 or 5 Gy of 137Cs ?-rays. Scanning electron microscopy demonstrated that irradiation facilitated structural disorganizations and detachment of the aortic endothelium. The Miles assay with an albumin-binding dye Evans Blue revealed that irradiation enhanced vascular permeability. Immunofluorescence staining showed that irradiation led to partial loss of the aortic endothelium (evidenced by a lack of adhesion molecule CD31 and 4',6-diamidino-2-phenylindole (DAPI) signals), a decrease in endothelial nitric oxide synthase and adherens junction protein (vascular endothelial (VE)-cadherin) in the aortic endothelium, along with an increase in inflammation (tumor necrosis factor (TNF)-?) and macrophage (F4/80) markers in the aorta. These findings suggest that irradiation produces vascular damage manifested as endothelial cell loss and increased vascular permeability, and that the decreased adherens junction and the increased inflammation lead to macrophage recruitment implicated in the early stage of atherosclerosis.

| S-EPMC7603246 | biostudies-literature

Carotenoid distribution in wild Japanese tree frogs (Hyla japonica) exposed to ionizing radiation in Fukushima.

Project description:The nuclear accident in the Fukushima prefecture released a large amount of artificial radionuclides that might have short- and long-term biological effects on wildlife. Ionizing radiation can be a harmful source of reactive oxygen species, and previous studies have already shown reduced fitness effects in exposed animals in Chernobyl. Due to their potential health benefits, carotenoid pigments might be used by animals to limit detrimental effects of ionizing radiation exposure. Here, we examined concentrations of carotenoids in blood (i.e. a snapshot of levels in circulation), liver (endogenous carotenoid reserves), and the vocal sac skin (sexual signal) in relation to the total radiation dose rates absorbed by individual (TDR from 0.2 to 34 µGy/h) Japanese tree frogs (Hyla japonica). We found high within-site variability of TDRs, but no significant effects of the TDR on tissue carotenoid levels, suggesting that carotenoid distribution in amphibians might be less sensitive to ionizing radiation exposure than in other organisms or that the potential deleterious effects of radiation exposure might be less significant or more difficult to detect in Fukushima than in Chernobyl due to, among other things, differences in the abundance and mixture of each radionuclide.

| S-EPMC5943346 | biostudies-literature

Modeling of DNA Damage Repair and Cell Response in Relation to p53 System Exposed to Ionizing Radiation.

Project description:Repair of DNA damage induced by ionizing radiation plays an important role in the cell response to ionizing radiation. Radiation-induced DNA damage also activates the p53 system, which determines the fate of cells. The kinetics of repair, which is affected by the cell itself and the complexity of DNA damage, influences the cell response and fate via affecting the p53 system. To mechanistically study the influences of the cell response to different LET radiations, we introduce a new repair module and a p53 system model with NASIC, a Monte Carlo track structure code. The factors determining the kinetics of the double-strand break (DSB) repair are modeled, including the chromosome environment and complexity of DSB. The kinetics of DSB repair is modeled considering the resection-dependent and resection-independent compartments. The p53 system is modeled by simulating the interactions among genes and proteins. With this model, the cell responses to low- and high-LET irradiation are simulated, respectively. It is found that the kinetics of DSB repair greatly affects the cell fate and later biological effects. A large number of DSBs and a slow repair process lead to severe biological consequences. High-LET radiation induces more complex DSBs, which can be repaired by slow processes, subsequently resulting in a longer cycle arrest and, furthermore, apoptosis and more secreting of TGFβ. The Monte Carlo track structure simulation with a more realistic repair module and the p53 system model developed in this study can expand the functions of the NASIC code in simulating mechanical radiobiological effects.

| S-EPMC9569799 | biostudies-literature

Enhancing the antitumor activity of adriamycin and ionizing radiation.

Project description:Overexpression of manganese superoxide dismutase (MnSOD), when combined with certain chemicals that inhibit peroxide removal, increases cancer cell cytotoxicity. Elevating MnSOD levels in cells enhances the conversion of superoxide (O(2)(*-)) to hydrogen peroxide (H(2)O(2)), combined with inhibiting the removal of H(2)O(2), further increases H(2)O(2) levels, leading to increased cytotoxicity. We hypothesized that increasing endogenous O(2)(*-) production in cells that were pretreated with adenoviral MnSOD (AdMnSOD) plus 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) would lead to an increased level of intracellular H(2)O(2) accumulation and increased cell killing. The cytotoxic effects of Adriamycin or radiation, agents known to produce O(2)(*-), were determined in MDA-MB-231 breast cancer cells pretreated with AdMnSOD plus BCNU both in vitro and in vivo. In vitro, AdMnSOD plus BCNU sensitized cells to the cytotoxicity of Adriamycin or radiation. In vivo, AdMnSOD, BCNU, and Adriamycin or ionizing radiation inhibited tumor growth and prolonged survival. The results suggest that agents that produce O(2)(*-) in combination with AdMnSOD plus BCNU may represent a powerful new antitumor regimen against breast cancer.

| S-EPMC2688464 | biostudies-other

Regulation of DNA Damage Response and Homologous Recombination Repair by microRNA in Human Cells Exposed to Ionizing Radiation.

Project description:Ionizing radiation may be of both artificial and natural origin and causes cellular damage in living organisms. Radioactive isotopes have been used significantly in cancer therapy for many years. The formation of DNA double-strand breaks (DSBs) is the most dangerous effect of ionizing radiation on the cellular level. After irradiation, cells activate a DNA damage response, the molecular path that determines the fate of the cell. As an important element of this, homologous recombination repair is a crucial pathway for the error-free repair of DNA lesions. All components of DNA damage response are regulated by specific microRNAs. MicroRNAs are single-stranded short noncoding RNAs of 20-25 nt in length. They are directly involved in the regulation of gene expression by repressing translation or by cleaving target mRNA. In the present review, we analyze the biological mechanisms by which miRNAs regulate cell response to ionizing radiation-induced double-stranded breaks with an emphasis on DNA repair by homologous recombination, and its main component, the RAD51 recombinase. On the other hand, we discuss the ability of DNA damage response proteins to launch particular miRNA expression and modulate the course of this process. A full understanding of cell response processes to radiation-induced DNA damage will allow us to develop new and more effective methods of ionizing radiation therapy for cancers, and may help to develop methods for preventing the harmful effects of ionizing radiation on healthy organisms.

| S-EPMC7408912 | biostudies-literature

Ectoine protects DNA from damage by ionizing radiation.

Project description:Ectoine plays an important role in protecting biomolecules and entire cells against environmental stressors such as salinity, freezing, drying and high temperatures. Recent studies revealed that ectoine also provides effective protection for human skin cells from damage caused by UV-A radiation. These protective properties make ectoine a valuable compound and it is applied as an active ingredient in numerous pharmaceutical devices and cosmetics. Interestingly, the underlying mechanism resulting in protecting cells from radiation is not yet fully understood. Here we present a study on ectoine and its protective influence on DNA during electron irradiation. Applying gel electrophoresis and atomic force microscopy, we demonstrate for the first time that ectoine prevents DNA strand breaks caused by ionizing electron radiation. The results presented here point to future applications of ectoine for instance in cancer radiation therapy.

| S-EPMC5681641 | biostudies-literature

Ionizing radiation from Chernobyl affects development of wild carrot plants.

Project description:Radioactivity released from disasters like Chernobyl and Fukushima is a global hazard and a threat to exposed biota. To minimize the deleterious effects of stressors organisms adopt various strategies. Plants, for example, may delay germination or stay dormant during stressful periods. However, an intense stress may halt germination or heavily affect various developmental stages and select for life history changes. Here, we test for the consequence of exposure to ionizing radiation on plant development. We conducted a common garden experiment in an uncontaminated greenhouse using 660 seeds originating from 33 wild carrots (Daucus carota) collected near the Chernobyl nuclear power plant. These maternal plants had been exposed to radiation levels that varied by three orders of magnitude. We found strong negative effects of elevated radiation on the timing and rates of seed germination. In addition, later stages of development and the timing of emergence of consecutive leaves were delayed by exposure to radiation. We hypothesize that low quality of resources stored in seeds, damaged DNA, or both, delayed development and halted germination of seeds from plants exposed to elevated levels of ionizing radiation. We propose that high levels of spatial heterogeneity in background radiation may hamper adaptive life history responses.

| S-EPMC5159907 | biostudies-other

Proteomic Profiling for Serum Biomarkers in Mice Exposed to Ionizing Radiation.

Project description:In response to large-scale radiological incidents, rapid, accurate, and early triage biodosimeters are urgently required. In this study, we investigated candidate radiation-responsive biomarkers using proteomics approaches in mouse models. A total of 452 dysregulated proteins were identified in the serum samples of mice exposed to 0, 2, 5.5, 7, and 8 Gy at 6, 24, and 72 hours postirradiation. Ninety-eight proteins, including 46 at 6 hours, 36 at 24 hours, and 36 at 72 hours, were identified as radiation-responsive proteins (RRPs). Gene Ontology analysis showed the RRPs were involved in proteolysis, extracellular space, hydrolase activity, and carbohydrate binding. Kyoto Encyclopedia of Genes and Genome enrichment showed the RRPs were regulated in "the pentose phosphate pathway," "the proteasome," and "AGE-RAGE signaling in diabetic complications." There were 3 proteins changed and overlapped at all the 3 time points, 8 proteins changed at 6 and 24 hours, 4 proteins changed at 24 and 72hours, and 2 proteins changed at both 6 and 72 hours. Of these proteins, ORM2, HP, SAA1, SAA2, MBL2, COL1A1, and APCS were identified as candidate biomarkers for biodosimeter-based diagnosis through Pearson correlation analysis.

| S-EPMC6909274 | biostudies-literature

Lipidomic Profiling for Serum Biomarkers in Mice Exposed to Ionizing Radiation.

Project description:Radiation biodosimeters are required urgently for fast and accurate evaluation of absorbed dose for irradiated individuals. Lipidomics has appeared as a credible technique for identification and quantification of lipid for researching biomarker of diseases. We performed a lipidomic profile on mice serum at time points of 6, 24, and 72 hours after 0, 2, 5.5, 7, and 8 Gy irradiation to select radiation-responsive lipids and conducted Kyoto Encyclopedia of Genes and Genome pathway enrichment analysis to recognize the pathways and network changes. Then, Pearson correlation analysis was performed to evaluate the feasibility of radiation-responsive lipids to estimate radiation dose. Seven radiation-responsive lipids including PC (18:2/18:2), PC (18:0/18:2), Lyso PC 18:1, PC (18:0/20:4), SM (D18:0/24:1), PC (16:0/18:1), and Lyso PC 18:2 were identified in which glycerophospholipid metabolism presented as the most significant pathway, and they all presented good linear correlation with the irradiated dose. This study identified 7 radiation-responsive lipids in mice serum and certificate their feasibility of dose estimation as biodosimeters.

| S-EPMC7180312 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data