scholarly journals Distinct vascular genomic response of proton and gamma radiation

2018 ◽  
Author(s):  
Ricciotti Emanuela ◽  
Dimitra Sarantopoulou ◽  
Gregory R. Grant ◽  
Jenine K. Sanzari ◽  
Gabriel S. Krigsfeld ◽  
...  
Keyword(s):  
Gamma Radiation ◽  
Dose Response ◽  
Photon Radiation ◽  
Radiation Response ◽  
Whole Body ◽  
Proton Radiation ◽  
Vascular Effects ◽  
Radiation Induced ◽  
Total Body ◽  
Genomic Response

AbstractPurpose. The cardiovascular biology of proton radiotherapy is not well understood. We aimed to compare the genomic dose-response to proton and gamma radiation of the mouse aorta to assess whether their vascular effects may diverge.Materials and methods.We performed comparative RNA sequencing of the aorta following (4 hrs) total-body proton and gamma irradiation (0.5 - 200 cGy whole body dose, 10 dose levels) of conscious mice. A trend analysis identified genes that showed a dose response.Results.While fewer genes were dose-responsive to proton than gamma radiation (29 vs. 194 genes;q-value ≤ 0.1), the magnitude of the effect was greater. Highly responsive genes were enriched for radiation response pathways (DNA damage, apoptosis, cellular stress and inflammation;p-value ≤ 0.01). Gamma, but not proton radiation induced additionally genes in vasculature specific pathways. Genes responsive to both radiation types showed almost perfectly superimposable dose-response relationships.Conclusions.Despite the activation of canonical radiation response pathways by both radiation types, we detected marked differences in the genomic response of the murine aorta. Models of cardiovascular risk based on photon radiation may not accurately predict the risk associated with proton radiation.

scholarly journals Pegylated G-CSF Inhibits Blood Cell Depletion, Increases Platelets, Blocks Splenomegaly, and Improves Survival after Whole-Body Ionizing Irradiation but Not after Irradiation Combined with Burn

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Juliann G. Kiang ◽  
Min Zhai ◽  
Pei-Jyun Liao ◽  
David L. Bolduc ◽  
Thomas B. Elliott ◽  
...  
Keyword(s):  
Tissue Injury ◽  
Marrow Cell ◽  
Total Body Surface Area ◽  
Body Weight Loss ◽  
Cell Depletion ◽  
Photon Radiation ◽  
Whole Body ◽  
Life Threatening ◽  
Radiation Induced ◽  
Total Body

Exposure to ionizing radiation alone (radiation injury, RI) or combined with traumatic tissue injury (radiation combined injury, CI) is a crucial life-threatening factor in nuclear and radiological accidents. As demonstrated in animal models, CI results in greater mortality than RI. In our laboratory, we found that B6D2F1/J female mice exposed to60Co-γ-photon radiation followed by 15% total-body-surface-area skin burns experienced an increment of 18% higher mortality over a 30-day observation period compared to irradiation alone; that was accompanied by severe cytopenia, thrombopenia, erythropenia, and anemia. At the 30th day after injury, neutrophils, lymphocytes, and platelets still remained very low in surviving RI and CI mice. In contrast, their RBC, hemoglobin, and hematocrit were similar to basal levels. Comparing CI and RI mice, only RI induced splenomegaly. Both RI and CI resulted in bone marrow cell depletion. It was observed that only the RI mice treated with pegylated G-CSF after RI resulted in 100% survival over the 30-day period, and pegylated G-CSF mitigated RI-induced body-weight loss and depletion of WBC and platelets. Peg-G-CSF treatment sustained RBC balance, hemoglobin levels, and hematocrits and inhibited splenomegaly after RI. The results suggest that pegylated G-CSF effectively sustained animal survival by mitigating radiation-induced cytopenia, thrombopenia, erythropenia, and anemia.

scholarly journals Ghrelin Therapy Improves Survival after Whole-Body Ionizing Irradiation or Combined with Burn or Wound: Amelioration of Leukocytopenia, Thrombocytopenia, Splenomegaly, and Bone Marrow Injury

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Juliann G. Kiang ◽  
Min Zhai ◽  
Pei-Jyun Liao ◽  
Thomas B. Elliott ◽  
Nikolai V. Gorbunov
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cell ◽  
Tissue Injury ◽  
Marrow Cell ◽  
Total Body Surface Area ◽  
Body Weight Loss ◽  
Cell Depletion ◽  
Photon Radiation ◽  
Whole Body ◽  
Total Body

Exposure to ionizing radiation alone (RI) or combined with traumatic tissue injury (CI) is a crucial life-threatening factor in nuclear and radiological events. In our laboratory, mice exposed to60Co-γ-photon radiation (9.5 Gy, 0.4 Gy/min, bilateral) followed by 15% total-body-surface-area skin wounds (R-W CI) or burns (R-B CI) experienced an increment of ≥18% higher mortality over a 30-day observation period compared to RI alone. CI was accompanied by severe leukocytopenia, thrombocytopenia, erythropenia, and anemia. At the 30th day after injury, numbers of WBC and platelets still remained very low in surviving RI and CI mice. In contrast, their RBC, hemoglobin, and hematocrit were recovered towards preirradiation levels. Only RI induced splenomegaly. RI and CI resulted in bone-marrow cell depletion. In R-W CI mice, ghrelin (a hunger-stimulating peptide) therapy increased survival, mitigated body-weight loss, accelerated wound healing, and increased hematocrit. In R-B CI mice, ghrelin therapy increased survival and numbers of neutrophils, lymphocytes, and platelets and ameliorated bone-marrow cell depletion. In RI mice, this treatment increased survival, hemoglobin, and hematocrit and inhibited splenomegaly. Our novel results are the first to suggest that ghrelin therapy effectively improved survival by mitigating CI-induced leukocytopenia, thrombocytopenia, and bone-marrow injury or the RI-induced decreased hemoglobin and hematocrit.

Protective effects of erdosteine against nephrotoxicity caused by gamma radiation in male albino rats

2015 ◽  
Vol 35 (1) ◽  
pp. 21-28 ◽  
Author(s):  
AA Elkady ◽  
IM Ibrahim
Keyword(s):  
Body Weight ◽  
Gamma Radiation ◽  
Gamma Irradiation ◽  
Gastric Tube ◽  
Whole Body ◽  
Control Group ◽  
Albino Rats ◽  
Once Daily ◽  
Renal Lesions ◽  
Radiation Induced

The aim of this study was focused on investigating the possible protective effect of erdosteine against gamma radiation-induced renal lesions in male albino rats. Twenty-eight albino rats were divided into four equal groups as follows: control group, irradiated group (animals subjected to whole-body gamma irradiation at a dose of 5 Gy), treated group (each rat received 100 mg/kg body weight once daily, orally by gastric tube, erdosteine for 1 week), and treated irradiated group (each rat received 100 mg/kg body weight once daily, orally by gastric tube, erdosteine for 1 week, then exposed to whole-body gamma irradiation at a dose of 5 Gy). The results revealed that the administration of erdosteine to rats before irradiation significantly ameliorated the changes occurred in kidney function (creatinine and urea) compared with irradiated group. Also the changes in serum tumor necrosis factor α, interleukin 1β, and interleukin 6 activities were markedly improved compared with the corresponding values of irradiated group. Kidney catalase and glutathione peroxidase (GPx) activities and reduced glutathione concentration showed approximately normal level when compared with the irradiated group. The histopathological results showed distinctive pattern of renal lesions in irradiated group, while in treated irradiated group the renal tissues showed relatively well-preserved architecture. Erdosteine acts in the kidney as a potent scavenger of free radicals to prevent or ameliorate the toxic effects of gamma irradiation as shown in the biochemical and histopathological changes and might provide substantial protection against radiation-induced inflammatory damage.

Evaluation of Gamma Radiation-Induced Biochemical Changes in Skin for Dose Assesment: A Study on Small Experimental Animals

2018 ◽  
Vol 13 (02) ◽  
pp. 197-202
Author(s):  
Sandeep Kumar Soni ◽  
Mitra Basu ◽  
Priyanka Agrawal ◽  
Aseem Bhatnagar ◽  
Neelam Chhillar
Keyword(s):  
Radiation Dose ◽  
Gamma Radiation ◽  
Radiation Injury ◽  
Acute Radiation ◽  
Dose Assessment ◽  
Whole Body ◽  
Dependent Manner ◽  
Acute Radiation Injury ◽  
Radiation Induced ◽  
Dose Dependent

AbstractObjectiveResearchers have been evaluating several approaches to assess acute radiation injury/toxicity markers owing to radiation exposure. Keeping in mind this background, we assumed that whole-body irradiation in single fraction in graded doses can affect the antioxidant profile in skin that could be used as an acute radiation injury/toxicity marker.MethodsSprague-Dawley rats were treated with CO-60 gamma radiation (dose: 1-5 Gy; dose rate: 0.85 Gy/minute). Skin samples were collected (before and after radiation up to 72 hours) and analyzed for glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), and lipid peroxidation (LPx).ResultsIntra-group comparison showed significant differences in GSH, GPx, SOD, and CAT, and they declined in a dose-dependent manner from 1 to 5 Gy (P value<0.01, r value: 0.3-0.5). LPx value increased (P value<0.01, r value: 0.3-0.5) as the dose increased, except in 1 Gy (P value>0.05).ConclusionsThis study suggests that skin antioxidants were sensitive toward radiation even at a low radiation dose, which can be used as a predictor of radiation injury and altered in a dose-dependent manner. These biochemical parameters may have wider application in the evaluation of radiation-induced skin injury and dose assessment. (Disaster Med Public Health Preparedness. 2019;13:197–202).

scholarly journals Stochastic Thresholds: A Novel Explanation of Nonlinear Dose-Response Relationships for Stochastic Radiobiological Effects

Dose-Response ◽  
2005 ◽  
Vol 3 (4) ◽  
pp. dose-response.0 ◽  
Author(s):  
Bobby R. Scott
Keyword(s):  
Dna Repair ◽  
Transition Zone ◽  
Dose Response ◽  
Low Dose ◽  
Nuclear Dna ◽  
Complete Inhibition ◽  
Photon Radiation ◽  
High Fidelity ◽  
Stochastic Effects ◽  
Radiation Induced

New research data for low-dose, low- linear energy transfer (LET) radiation-induced, stochastic effects (mutations and neoplastic transformations) are modeled using the recently published NEOTRANS3 model. The model incorporates a protective, stochastic threshold (StoThresh) at low doses for activating cooperative protective processes considered to include presumptive p53-dependent, high-fidelity repair of nuclear DNA damage in competition with presumptive p53-dependent apoptosis and a novel presumptive p53-independent protective apoptosis mediated (PAM) process which selectively removes genomically compromised cells (mutants, neoplastic transformants, micronucleated cells, etc.). The protective StoThresh are considered to fall in a relatively narrow low-dose zone (Transition Zone A). Below Transition Zone A is the ultra-low-dose region where it is assumed that only low-fidelity DNA repair is activated along with presumably apoptosis. For this zone there is evidence for an increase in mutations with increases in dose. Just above Transition Zone A, a Zone of Maximal Protection (suppression of stochastic effects) arises and is attributed to maximal cooperation of high-fidelity, DNA repair/apoptosis and the PAM process. The width of the Zone of Maximal Protection depends on low-LET radiation dose rate and appears to depend on photon radiation energy. Just above the Zone of Maximal Protection is Transition Zone B, where deleterious StoThresh for preventing the PAM process fall. Just above Transition Zone B is a zone of moderate doses where complete inhibition of the PAM process appears to occur. However, for both Transition Zone B and the zone of complete inhibition of the PAM process, high-fidelity DNA repair/apoptosis are presumed to still operate. The indicated protective and deleterious StoThresh lead to nonlinear, hormetic-type dose-response relationships for low-LET radiation-induced mutations, neoplastic transformation and, presumably, also for cancer.

scholarly journals Radioprotective Effects of Gallic Acid in Mice

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Gopakumar Gopinathan Nair ◽  
Cherupally Krishnan Krishnan Nair
Keyword(s):  
Bone Marrow ◽  
Gamma Radiation ◽  
Gallic Acid ◽  
Chromosomal Aberrations ◽  
Bone Marrow Cells ◽  
Membrane Lipids ◽  
Lethal Dose ◽  
Whole Body ◽  
Radiation Induced ◽  
Marrow Cells

Radioprotecting ability of the natural polyphenol, gallic acid (3,4,5-trihydroxybenzoic acid, GA), was investigated in Swiss albino mice. Oral administration of GA (100 mg/kg body weight), one hour prior to whole body gamma radiation exposure (2–8 Gy; 6 animals/group), reduced the radiation-induced cellular DNA damage in mouse peripheral blood leukocytes, bone marrow cells, and spleenocytes as revealed by comet assay. The GA administration also prevented the radiation-induced decrease in the levels of the antioxidant enzyme, glutathione peroxidise (GPx), and nonprotein thiol glutathione (GSH) and inhibited the peroxidation of membrane lipids in these animals. Exposure of mice to whole body gamma radiation also caused the formation of micronuclei in blood reticulocytes and chromosomal aberrations in bone marrow cells, and the administration of GA resulted in the inhibition of micronucleus formation and chromosomal aberrations. In irradiated animals, administration of GA elicited an enhancement in the rate of DNA repair process and a significant increase in endogenous spleen colony formation. The administration of GA also prevented the radiation-induced weight loss and mortality in animals (10 animals/group) exposed to lethal dose (10 Gy) of gamma radiation. (For every experiment unirradiated animals without GA administration were taken as normal control; specific dose (Gy) irradiated animals without GA administration serve as radiation control; and unirradiated GA treated animals were taken as drug alone control).

Effect of Dibenamine on LD100 following supralethal dose of total body gamma radiation

1961 ◽  
Vol 201 (2) ◽  
pp. 347-348
Author(s):  
Stanley W. Handford ◽  
Paul W. Johnson
Keyword(s):  
Gamma Radiation ◽  
Survival Time ◽  
Blocking Agent ◽  
Acute Radiation ◽  
Radiation Sickness ◽  
Whole Body ◽  
Acute Radiation Sickness ◽  
Control Groups ◽  
Total Body ◽  
Adrenergic Blocking

Dibenamine, an adrenergic blocking agent, was administered to dogs immediately before they were subjected to a supralethal dose of whole body radiation. No significant differences in the course of acute radiation sickness or survival time (LD100) between the treated and sham-treated control groups were observed.

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