Possible relationship between mitochondrial changes and oxidative stress under low dose-rate irradiation.
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ABSTRACT:
SUBMITTER: Meng Q
PROVIDER: S-EPMC8405122 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The effects of galactic cosmic radiation on reproductive physiology remain largely unknown. We determined the impact of near-continuous low-dose-rate Californium-252 neutron irradiation (1 mGy/day) as a space-relevant analog on litter size and number of resorptions at embryonic day (E) 12.5 (n=19 radiated dams, n=20 controls) and litter size, number of resorptions, fetal growth, and placental signaling and transcriptome (RNA sequencing) at E18.5 (n=21 radiated dams, n=20 controls) in pregnant mice. A significantly increased early resorption rate and decreased placental weight was observed in irradiated mice. There were no statistically significant differences in litter size, fetal weight, length, or malformation rate between the groups. Near-continuous radiation had no significant effects on mechanistic target of rapamycin (mTOR), endoplasmic reticulum stress or inflammatory signaling, rate of double-stranded DNA breaks, and had minimal effects on gene expression in the placenta. These data suggest that near-continuous, low-level galactic cosmic radiation has a limited impact on pregnancy outcomes.
2024-07-01 | GSE271237 | GEO
Project description:Low-dose irradiation (LDI) has been used in clinics to treat human diseases, including chronic inflammation. This study assessed the effects of LDI on the inflammatory response of activated mouse primary peritoneal macrophages, and the underlying signal pathways. Primary peritoneal macrophages were isolated from mice and then incubated with lipopolysaccharide (LPS)-coated Ti microparticles (Ti-positive control) with or without brief exposure to LDI (X-ray, 0.5 Gy) 1 h later (Ti-LDI group) or left untreated in culture medium (Ti-negative control). The macrophages were then subjected to qRT-PCR, Western blot, cell viability CCK-8 assay, and ELISA. qRT-PCR analysis revealed the Ti-LDI group expressed significantly lower levels of IL-1β, IL-6, and TNF-α mRNA than those of the Ti-positive control group, while the ELISA data showed that Ti-LDI group had significantly lower secretion of IL-1β, IL-6, and TNF-α proteins. The most significant reduction associated with LDI was the secretion TNF-α protein, which barely increased from 13 to 25 h after treatment. Western blot data demonstrated that phosphorylation of p65 and ERK was much lower in the Ti-LDI group than in the controls. The data from the current study suggests that LDI of activated mouse macrophages was associated with significantly lower inflammation responses, compared with non-exposed activated macrophages, which was possibly through inhibition of the NF-κB and ERK pathways.
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Project description:Although safe doses of radiation have been determined, concerns about the harmful effects of low-dose radiation persist. In particular, to date, few studies have investigated the correlation between low-dose radiation and disease development. Asthma is a common chronic inflammatory airway disease that is recognized as a major public health problem. In this study, we evaluated the effects of low-dose-rate chronic irradiation on allergic asthma in a murine model. Mice were sensitized and airway-challenged with ovalbumin (OVA) and were exposed to continuous low-dose-rate irradiation (0.554 or 1.818 mGy/h) for 24 days after initial sensitization. The effects of chronic radiation on proinflammatory cytokines and the activity of matrix metalloproteinase-9 (MMP-9) were investigated. Exposure to low-dose-rate chronic irradiation significantly decreased the number of inflammatory cells, methylcholine responsiveness (PenH value), and the levels of OVA-specific immunoglobulin E, interleukin (IL)-4, and IL-5. Furthermore, airway inflammation and the mucus production in lung tissue were attenuated and elevated MMP-9 expression and activity induced by OVA challenge were significantly suppressed. These results indicate that low-dose-rate chronic irradiation suppresses allergic asthma induced by OVA challenge and does not exert any adverse effects on asthma development. Our findings can potentially provide toxicological guidance for the safe use of radiation and relieve the general anxiety about exposure to low-dose radiation.
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Project description:PurposeSpace travel is associated with an exposure to low-dose rate ionizing radiation and the microgravity environment, both of which may lead to impairments in cardiac function. We used a mouse model to determine short- and long-term cardiac effects to simulated microgravity (hindlimb unloading; HU), continuous low-dose rate ?-irradiation, or a combination of HU and low-dose rate ?-irradiation.MethodsCardiac tissue was obtained from female, C57BL/6J mice 7 days, 1 month, 4 months, and 9 months following the completion of a 21 day exposure to HU or a 21 day exposure to low-dose rate ?-irradiation (average dose rate of 0.01 cGy/h to a total of 0.04 Gy), or a 21 day simultaneous exposure to HU and low-dose rate ?-irradiation. Immunoblot analysis, rt-PCR, high-performance liquid chromatography, and histology were used to assess inflammatory cell infiltration, cardiac remodeling, oxidative stress, and the methylation potential of cardiac tissue in 3 to 6 animals per group.ResultsThe combination of HU and ?-irradiation demonstrated the strongest increase in reduced to oxidized glutathione ratios 7 days and 1 month after treatment, but a difference was no longer apparent after 9 months. On the other hand, no significant changes in 4-hydroxynonenal adducts was seen in any of the groups, at the measured endpoints. While manganese superoxide dismutase protein levels decreased 9 months after low-dose ?-radiation, no changes were observed in expression of catalase or Nrf2, a transcription factor that determines the expression of several antioxidant enzymes, at the measured endpoints. Inflammatory marker, CD-2 protein content was significantly decreased in all groups 4 months after treatment. No significant differences were observed in ?-smooth muscle cell actin protein content, collagen type III protein content or % total collagen.ConclusionsThis study has provided the first and relatively broad analysis of small molecule and protein markers of oxidative stress, T-lymphocyte infiltration, and cardiac remodeling in response to HU with simultaneous exposure to low-dose rate ?-radiation. Results from the late observation time points suggest that the hearts had mostly recovered from these two experimental conditions. However, further research is needed with larger numbers of animals for a more robust statistical power to fully characterize the early and late effects of simulated microgravity combined with exposure to low-dose rate ionizing radiation on the heart.
| S-EPMC5498037 | biostudies-literature
Project description:Measuring global gene expression using cDNA or oligonucleotide microarrays is an effective approach to understanding the complex mechanisms of the effects of radiation. However, few studies have been carried out that investigate gene expression in vivo after prolonged exposure to low-dose-rate radiation. In this study, C57BL/6J mice were continuously irradiated with γ-rays for 485 days at dose-rates of 0.032 – 13 μGy/min. Gene expression profiles in the kidney and testis from irradiated and unirradiated mice were analyzed, and differentially expressed genes were identified. A combination of pathway analysis and hierarchical clustering of differentially expressed genes revealed that expression of genes involved in mitochondrial oxidative phosphorylation was elevated in the kidney after irradiation at the dose-rates of 0.65 μGy/min and 13 μGy/min. Expression of cell cycle-associated genes was not profoundly modulated in the kidney, in contrast to the response to acute irradiation, suggesting a threshold in the dose-rate for modulation of the expression of cell cycle-related genes in vivo following exposure to radiation. We demonstrated that changes to the gene expression profile in the testis were largely different from those in the kidney. The Gene Ontology categories “DNA metabolism”, “response to DNA damage” and “DNA replication” overlapped significantly with the clusters of genes whose expression decreased with an increase in the dose-rate to the testis. These observations provide a fundamental insight into the organ-specific responses to low-dose-rate radiation. Key Words: kidney, low-dose-rate, radiation, microarray, mitochondrial oxidative phosphorylation, testis
2009-05-27 | GSE14290 | GEO
Project description:BACKGROUND:Radiotherapy remains one of the cornerstones to improve the outcome of colorectal cancer (CRC) patients. Radiotherapy of the CRC not only help to destroy cancer cells but also remodel the tumour microenvironment by enhancing tumour-specific tropism of bone marrow-derived mesenchymal stromal cell (BM-MSC) from the peripheral circulation. However, the role of local MSCs and recruited BM-MSC under radiation were not well defined. Indeed, the functions of BM-MSC without irradiation intervention remained controversial in tumour progression: BM-MSC was previously shown to modulate the immune function of major immune cells, resulting in an impaired immunological sensitivity and to induce an increased risk of tumour recurrence. In contrast, it could also secrete various cytokines and possess anticancer effect. METHODS:Three co-cultivation modules, 3D culture modules, and cancer organoids were established. The induction of cytokines secretion in hBM-MSCs after irradiation was analysed by ELISA array and flow cytometry. AutoMac separator was used to separate hBM-MSC and CRC automatically. Cells from the co-cultured group and the control group were then irradiated by UV-C lamp and X-ray. Proliferation assay and viability assay were performed. RESULTS:In this study, we show that BM-MSCs can induce the EMT progression of CRC cells in vitro. When irradiated with low doses of ultraviolet radiation and X-rays, BM-MSCs show an anti-tumour effect by secreting certain cytokine (TNF-?, IFN-?) that lead to the inhibition of proliferation and induction of apoptosis of CRC cells. This was further verified in a 3D culture model of a CRC cell in vitro. Furthermore, irradiation on the co-culture system induced the cleavage of caspase3, and attenuated the phosphorylation of phosphatidylinositol 3-kinase (PI3K)/AKT and extracellular signal-regulated kinase in cancer cells. The signal pathways above might contribute to the cancer cell death. CONCLUSIONS:Taken together, we show that BM-MSC can potentially promote the effect of radiotherapy in CRC.
| S-EPMC5808030 | biostudies-literature
Project description:Measuring global gene expression using cDNA or oligonucleotide microarrays is an effective approach to understanding the complex mechanisms of the effects of radiation. However, few studies have been carried out that investigate gene expression in vivo after prolonged exposure to low-dose-rate radiation. In this study, C57BL/6J mice were continuously irradiated with ?-rays for 485 days at dose-rates of 0.032 – 13 ?Gy/min. Gene expression profiles in the kidney and testis from irradiated and unirradiated mice were analyzed, and differentially expressed genes were identified. A combination of pathway analysis and hierarchical clustering of differentially expressed genes revealed that expression of genes involved in mitochondrial oxidative phosphorylation was elevated in the kidney after irradiation at the dose-rates of 0.65 ?Gy/min and 13 ?Gy/min. Expression of cell cycle-associated genes was not profoundly modulated in the kidney, in contrast to the response to acute irradiation, suggesting a threshold in the dose-rate for modulation of the expression of cell cycle-related genes in vivo following exposure to radiation. We demonstrated that changes to the gene expression profile in the testis were largely different from those in the kidney. The Gene Ontology categories “DNA metabolism”, “response to DNA damage” and “DNA replication” overlapped significantly with the clusters of genes whose expression decreased with an increase in the dose-rate to the testis. These observations provide a fundamental insight into the organ-specific responses to low-dose-rate radiation. Key Words: kidney, low-dose-rate, radiation, microarray, mitochondrial oxidative phosphorylation, testis 3 biological replicates for each experimental group were analysed. GSE14290_Kidney_raw_data.csv contains the raw data for GSM357146, GSM357425, GSM357426, GSM357452 to GSM357460. GSE14290_Testis_raw_data.csv contains the raw data for GSM357471 to GSM357482. In these files, the sample identifiers are included in the column headers.
2009-05-27 | E-GEOD-14290 | biostudies-arrayexpress
Project description:Cancer stem cell (CSC) is thought to be the major cause of radio-resistance and relapse post radiotherapy (RT). Recently ultra-high dose rate "FLASH-RT" evokes great interest for its decreasing normal tissue damages while maintaining tumor responses compared with conventional dose rate RT. However, the killing effect and mechanism of FLASH irradiation (FLASH-IR) on CSC and normal cancer cell are still unclear. Presently the radiation induced death profile of CSC and normal cancer cell were studied. Cells were irradiated with FLASH-IR (∼109 Gy/s) at the dose of 6-9 Gy via laser-accelerated nanosecond particles. Then the ratio of apoptosis, pyroptosis and necrosis were determined. The results showed that FLASH-IR can induce apoptosis, pyroptosis and necrosis in both CSC and normal cancer cell with different ratios. And CSC was more resistant to radiation than normal cancer cell under FLASH-IR. Further experiments tracing lysosome and autophagy showed that CSCs had higher levels of lysosome and autophagy. Taken together, our results suggested that the radio-resistance of CSC may associate with the increase of lysosome-mediated autophagy, and the decrease of apoptosis, necrosis and pyroptosis. To our limited knowledge, this is the first report shedding light on the killing effects and death pathways of CSC and normal cancer cell under FLASH-IR. By clarifying the death pathways of CSC and normal cancer cell under FLASH-IR, it may help us improve the understanding of the radio-resistance of CSC and thus help to optimize the future clinical FLASH treatment plan.
| S-EPMC8116574 | biostudies-literature
Project description:BackgroundThis study set out to evaluate the effect of dose rate on normal tissues (the lung, in particular) and the variation in the treatment efficiency as determined by the monitor unit (MU) and energy applied in Linac-based volumetric arc therapy (VMAT) total marrow irradiation (TMI).MethodsLinac-based VMAT plans were generated for the TMI for six patients. The planning target volume (PTV) was divided into six sub-volumes, each of which had their own isocenter. To examine the effect of the dose rate and energy, a range of MU rates (40, 60, 80, 100, 300, and 600 MU/min) were selected for 6, 10, and 15 MV. All the plans were verified by portal dosimetry.ResultsThe dosimetric parameters for the target and normal tissue were consistent in terms of the energy and MU rate. The beam-on time was changed from 59.6 to 6 min for 40 and 600 MU/min. When 40 MU/min was set for the lung, the dose rate delivered to the lung was less than 6 cGy/min (that is, 90%), while the beam-on time was approximately 10 min. The percentage volume of the lung receiving 20 cGy/min was 1.47, 3.94, and 6.22% at 6, 10, and 15 MV, respectively. However, for 600 MU/min, the total lung volume received over 6 cGy/min regardless of the energy, and over 20 cGy/min for 10 and 15 MV (i.e., 54.4% for 6 MV).ConclusionsIn TMI treatment, reducing the dose rate administered to the lung can decrease the incidence of pulmonary toxicity. To reduce the probability of normal tissue complications, the selection of the lowest MU rate is recommended for fields including the lung. To minimize the total treatment time, the maximum MU rate can be applied to other fields.
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Project description:A recently introduced brachytherapy system for partial breast irradiation, MammoSite, consists of a balloon applicator filled with contrast solution and a catheter for insertion of an 192Ir high-dose-rate (HDR) source. In using this system, the treatment dose is typically prescribed to be delivered 1 cm from the balloon's surface. Most treatment-planning systems currently in use for brachytherapy procedures use water-based dosimetry with no correction for heterogeneity. Therefore, these systems assume that full scatter exists regardless of the amount of tissue beyond the prescription line. This assumption might not be a reasonable one, especially when the tissue beyond the prescription line is thin. In such a case, the resulting limited scatter could cause an underdose to be delivered along the prescription line. We used Monte Carlo simulations to investigate how the thickness of the tissue between the surface of the balloon and the skin or lung affected the treatment dose delivery. Calculations were based on a spherical water phantom with a diameter of 30 cm and balloons with diameters of 4 cm, 5 cm, and 6 cm. The dose modification factor is defined as the ratio of the dose rate at the typical prescription distance of 1 cm from the balloon's surface with full scatter obtained using the water phantom to the dose rate with a finite tissue thickness (from 0 cm to 10 cm) beyond the prescription line. The dose modification factor was found to be dependent on the balloon diameter and was 1.098 for the 4-cm balloon and 1.132 for the 6-cm balloon with no tissue beyond the prescription distance at the breast-skin interface. The dose modification factor at the breast-lung interface was 1.067 for the 4-cm balloon and 1.096 for the 6-cm balloon. Even 5 cm of tissue beyond the prescription distance could not result in full scatter. Thus, we found that considering the effect of diminished scatter is important to accurate dosimetry. Not accounting for the dose modification factor may result in delivering a lower dose than is prescribed.
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