Radiation Damage

Source: www.ncbi.nlm.nih.gov --- 17 hours ago
Related Articles Elevated DNA Damage in a mouse model of oxidative stress: impacts of ionizing Radiation and a protective dietary supplement. Mutagenesis. 2008 Jul 21; Authors: Lemon JA, Rollo CD, Boreham DR Transgenic growth hormone (Tg) mice express elevated free radical processes and a progeroid syndrome of accelerated ageing. We examined bone marrow cells of Tg mice and their normal (Nr) siblings for three markers of DNA Damage and assessed the impact of free radical stress using ionizing Radiation. We also evaluated the Radiation protection afforded by a dietary supplement that we previously demonstrated to extend longevity and reduce cognitive ageing of Nr and Tg mice. Spectral karyotyping revealed few spontaneous chromosomal aberrations in Nr or Tg. Tg mice, however, had significantly greater constitutive levels of both gammaH2AX and 8-hydroxy-deoxyguanosine (8-OHdG) compared to Nr. When exposed to a 2-Gy whole-body dose of ionizing Radiation, both Nr and Tg mice showed significant increases in DNA Damage. Compared to Nr mice, irradiated Tg mice had dramatically higher levels of gammaH2AX foci and double the levels of chromosomal aberrations. In unirradiated mice, the dietary supplement significantly reduced constitutive gammaH2AX and 8-OHdG in both Nr and Tg mice (normalizing both gammaH2AX and 8-OHdG in Tg), with little difference in gammaH2AX and 8-OHdG over constitutive levels. Induced chromosomal aberrations were also redu ...

Source: www.ncbi.nlm.nih.gov --- 14 days ago
Related Articles Relationships between acute reactions to radiotherapy in head and neck cancer patients and parameters of Radiation-induced DNA Damage and repair in their lymphocytes. Int J Radiat Biol. 2008 May 9;:1-8 Authors: Rzeszowska-Wolny J, Palyvoda O, Polanska J, Wygoda A, Hancock R Purpose: To study the relationship between lymphocyte radiosensitivity measured in vitro and acute reactions to radiotherapy in patients with head and neck cancer. Materials and methods: Acute reactions were measured in 34 patients using the Dische scale. Lymphocyte radiosensitivity was measured using the alkaline comet assay, the micronucleus assay, the nuclear division index and morphological assessment of apoptosis. Results: There was a weak, statistically significant correlation between in vitro radiosensitivity measured as the rate of DNA Damage repair and the cumulative Radiation dose exerting the maximum acute reaction scored (r = -0.366, p = 0.039, n = 34). Subgroup analyses showed that for patients with a low level of Radiation-induced DNA Damage there was a statistically significant relationship between lymphocyte radiosensitivity measured as inhibition of proliferation and acute toxicity (r = -0.621, p = 0.007, n = 18). For patients with a high level of residual DNA Damage, there was a relationship between lymphocyte radiosensitivity measured using the micronucleus assay and acute toxicity (r = -0.597, p = 0.023, n = 14). Conclusions: Com ...

Source: www.ncbi.nlm.nih.gov --- 46 days ago
Related Articles Induction of NKG2D ligands by gamma Radiation and tumor necrosis factor-alpha may participate in the tissue Damage during acute graft-versus-host disease. Transplantation. 2008 Mar 27;85(6):911-5 Authors: Gannagé M, Buzyn A, Bogiatzi SI, Lambert M, Soumelis V, Dal Cortivo L, Cavazzana-Calvo M, Brousse N, Caillat-Zucman S Immunopathology of acute graft-versus-host disease (aGVHD) involves secretion of proinflammatory cytokines with subsequent expression of danger signals by injured host tissues. This explanation, however, does not explain the cluster of aGVHD target organs (skin, gut, and liver). NKG2D ligands (MICA/B and ULBP1-3 proteins) are stress-induced molecules that act as danger signals to alert NK and alphabeta or gammadelta CD8 T cells through engagement of the activating NKG2D receptor. We observed a strong and reversible induction of MICA/B expression in skin and liver sections during aGVHD. Tumor necrosis factor-alpha and gamma-Radiation up-regulated expression of MICA/B and ULBP proteins in vitro on skin and intestine epithelial cell lines and ex vivo in normal skin explants. This NKG2D-ligand induction was regulated by a complex interplay between NFkB and JNK activation pathways. Our data suggest that NKG2D ligand induction might participate in the amplification loop that leads to tissue Damage during aGVHD. PMID: 18360276 [PubMed - indexed for MEDLINE] ...

Source: www.ncbi.nlm.nih.gov --- 27 days ago
Related Articles Reciprocal paracrine interactions between normal human epithelial and mesenchymal cells protect cellular DNA from Radiation-induced Damage. Int J Radiat Oncol Biol Phys. 2008 Jun 1;71(2):567-77 Authors: Nakazawa Y, Saenko V, Rogounovitch T, Suzuki K, Mitsutake N, Matsuse M, Yamashita S PURPOSE: To explore whether interactions between normal epithelial and mesenchymal cells can modulate the extent of Radiation-induced DNA Damage in one or both types of cells. METHODS AND MATERIALS: Human primary thyrocytes (PT), diploid fibroblasts BJ, MRC-5, and WI-38, normal human mammary epithelial cells (HMEC), and endothelial human umbilical cord vein endothelial cells (HUV-EC-C), cultured either individually or in co-cultures or after conditioned medium transfer, were irradiated with 0.25 to 5 Gy of gamma-rays and assayed for the extent of DNA Damage. RESULTS: The number of gamma-H2AX foci in co-cultures of PT and BJ fibroblasts was approximately 25% lower than in individual cultures at 1 Gy in both types of cells. Reciprocal conditioned medium transfer to individual cultures before irradiation resulted in approximately a 35% reduction of the number gamma-H2AX foci at 1 Gy in both types of cells, demonstrating the role of paracrine soluble factors. The DNA-protected state of cells was achieved within 15 min after conditioned medium transfer; it was reproducible and reciprocal in several lines of epithelial cells and fibroblasts, f ...

Source: www.medicalnewstoday.com --- 44 days ago
Researchers with the University of Pittsburgh Cancer Institute (UPCI) have identified a gene that may play a role in promoting Radiation-induced intestinal Damage. The research, published by Cell Press in the June issue of the journal Cell Stem Cell, could lead to new strategies for protecting normal tissues from Radiation during cancer treatment. ...

Source: dissertations.ub.rug.nl --- 17 days ago
In dit proefschrift worden de structuurveranderingen ten gevolge van stralingsschade behandeld, in het bijzonder schade ontstaan door implantatie van zware deeltjes in fcc metalen. Gedetailleerde kennis van deze structuurveranderingen is van belang gezien de grote en soms gunstige invloed hiervan op de materiaaleigenschappen. Het is bekend, dat men door implantatie in een zeer dunne oppervlaktelaag de mechanische eigenschappen van metalen, b.v. de oppervlakte hardheid, de slijtagevastheid en de corrosievastheid, en mogelijk ook de vermoeiingslevensduur sterk kan beinvloeden. ... Zie: Samenvatting ...

Source: stacks.iop.org --- 36 days ago
Author(s): Mike Partridge Affiliation(s): The Institute of Cancer Research, Downs Road, Sutton, SM2 5PT, UK ...

Source: www.postchronicle.com --- 37 days ago
Transistors based on a material created by U.S. scientists have been attached to the exterior of the International Space Station for Radiation testing. ... ...

Source: www.engineeringvillage.com --- 11 days ago
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Source: www.proteomonitor.com --- 10 days ago
Despite the ongoing risk of radioactive dirty bombs set off by terrorists, as well as run-of-the-mill nuclear disasters, there are currently no protein biomarkers that could help detect early signs of injury brought on by Radiation exposure. But researchers have been studying changes in rat protein levels after Radiation exposure and used proteomic technology to detect those changes in rat urine. ...

Source: www.ncbi.nlm.nih.gov --- 14 days ago
Related Articles Effect of prolonging Radiation delivery time on retention of gamma-H2AX. Radiat Oncol. 2008 Jun 27;3(1):18 Authors: Moiseenko V, Banath JP, Duzenli C, Olive PL ABSTRACT: Background and purpose: Compared to conventional external beam radiotherapy, IMRT requires significantly more time to deliver the dose. Prolonging dose delivery potentially increases DNA repair which would reduce the biological effect. We questioned whether retention of gammaH2AX, a measure of lack of repair of DNA Damage, would decrease when dose delivery was protracted. Materials and methods: Exponentially growing SiHa cervical carinoma cells were irradiated with 6 MV photons in a water tank using a VarianEX linear accelerator. Cells held at 37oC received 2 Gy in 0.5 min and 4 Gy in 1 min. To evaluate effect of dose delivery prolongation, 2 and 4 Gy were delivered in 30 and 60 min. After 24h recovery, cells were analyzed for clonogenic survival and for residual H2AX as measured using flow cytometry. RESULTS: Increasing the dose delivery time from 0.5 or 1 min to 30 or 60 min produced a signficant increase in cell survival from 0.45 to 0.48 after 2 Gy, and from 0.17 to 0.20 after 4 Gy. Expression of residual gammaH2AX decreased from 1.27 to 1.22 relative to background after 2 Gy and 1.46 to 1.39 relative to background after 4 Gy, but differences were not statistically significant. The relative differences in the slopes of residual gammaH2AX versus dose ...

Source: www.ncbi.nlm.nih.gov --- 19 days ago
Changes in phosphorylation of histone H2A.X and p53 in response of peripheral blood lymphocytes to gamma irradiation. Acta Biochim Pol. 2008;55(2):381-90 Authors: Vilasová Z, Rezácová M, Vávrová J, Tichý A, Vokurková D, Zoelzer F, Reháková Z, Osterreicher J, Lukásová E The main aim of this study was to compare the reaction of quiescent and proliferating, i.e. phytohemagglutinin (PHA)-stimulated, human peripheral blood mononuclear cells (PBMCs) to gamma-Radiation, and analyse changes of proteins related to repair of DNA Damage and apoptosis, such as gammaH2A.X, p53, p53 phosphorylation at serines-15 and -392, and p21 and their dose dependence. Freshly isolated PBMCs in peripheral blood are predominantly quiescent, in G(0) phase, and with very low amounts of proteins p53 and p21. Using confocal microscopy we detected dose dependent (0.5-5 Gy) induction of foci containing gammaH2A.X (1 h after gamma-ray exposure), which are formed around Radiation-induced double strand breaks of DNA. Apoptosis was detected from 24 h after irradiation by the dose of 4 Gy onwards by Annexin V binding and lamin B cleavage. Seventy two hours after irradiation 70% of CD3(+) lymphocytes were A(+). Neither increase in p53 nor its phosphorylation on serine-392 after irradiation was detected in these cells. However, massive increase in p21 (cyclin-dependent kinase inhibitor 1A) was detected after irradiation, which can be responsible for late occurrence of apoptosi ...

Source: www.ncbi.nlm.nih.gov --- 5 days ago
Related Articles Space Radiation-induced inhibition of neurogenesis in the hippocampal dentate gyrus and memory impairment in mice: ameliorative potential of the melatonin metabolite, AFMK. J Pineal Res. 2008 Jul 2; Authors: Manda K, Ueno M, Anzai K Evaluation of potential health effects from high energy charged particle Radiation exposure during long duration space travel is important for the future of manned missions. Cognitive health of an organism is considered to be maintained by the capacity of hippocampal precursors to proliferate and differentiate. Environmental stressors including irradiation have been shown to inhibit neurogenesis and are associated with the onset of cognitive impairments. The present study reports on the protective effects of N(1)-acetyl-N(2)-formyl-5-methoxykynuramine (AFMK), a melatonin metabolite, against high energy charged particle Radiation-induced oxidative Damage to the brain. We observed that Radiation exposure (2.0 Gy of 500 MeV/nucleon (56)Fe beams, a ground-based model of space Radiation) impaired the spatial memory of mice at later intervals without affecting the motor activities. AFMK pretreatment significantly ameliorated these neurobehavioral ailments. Radiation-induced changes in the population of immature and proliferating neurons in the dentate gyrus were localized using anti-doublecortin (Dcx) and anti-Ki-67 expression. AFMK pretreatment significantly inhibited the loss of Dcx and Ki-67 p ...

Source: www.ncbi.nlm.nih.gov --- 22 days ago
Related Articles Is There an Entity of Chemically Induced BCR-ABL-Positive Chronic Myelogenous Leukemia? Oncologist. 2008 Jun;13(6):645-54 Authors: Lichtman MA Advances in the therapy of malignancy have been accompanied by an increased frequency of cases of secondary acute myelogenous leukemia and related clonal cytopenias and oligoblastic (subacute) myelogenous leukemia (myelodysplastic syndromes). The acute myelogenous leukemia incidence can be increased by high-dose acute ionizing Radiation exposure, alkylating agents, topoisomerase II inhibitors, possibly other DNA-damaging therapeutic agents, heavy, prolonged cigarette smoking, and high dose-time exposure to benzene, the latter less frequently seen in industrialized countries with worksite regulations. Acute myelogenous leukemia and myelodysplastic syndromes may result from innumerable primary types of chromosome Damage. In the case of chronic myelogenous leukemia, a specific break in chromosome bands 9q34 and 22q11 must occur to result in the causal fusion oncogene (BCR-ABL). A review of 11 studies of the chromosomal abnormalities found in presumptive cases of cytotoxic therapy-induced leukemia and of 40 studies of the subtypes of leukemia that occur following cytotoxic therapy for other cancers has not provided evidence of an increased risk for chemically induced BCR-ABL-positive chronic myelogenous leukemia. Studies of the effects of alkylating agents, topoisomerase inhibitors, ...

Source: www.ncbi.nlm.nih.gov --- 22 days ago
Related Articles Thyroidectomies from patients with history of therapeutic Radiation during childhood and adolescence have a unique mutational profile. Mod Pathol. 2008 Jun 27; Authors: Assaad A, Voeghtly L, Hunt JL Radiation in childhood is a known risk factor for thyroid carcinoma, but may also be related to benign nodular hyperplasias. Recent evidence from comparative genomic hybridization indicates that Radiation can induce clonal DNA Damage in cultured rat thyrocytes. We used a loss of heterozygosity analysis for the loci identified by comparative genomic hybridization to study human thyroids. Thyroids from patients with a history of Radiation, patients who had recent therapeutic external beam Radiation for laryngeal carcinoma, and patients who had no Radiation and underwent incidental thyroidectomy with laryngectomy for laryngeal carcinoma were included. PCR was performed for 18 different genetic loci defined by prior reported comparative genomic hybridization study. A semiquantitative capillary electrophoresis analysis was used and frequency of allelic loss was calculated from the number of losses/the number of informative loci. A total of 40 cases of thyroids from patients with childhood Radiation, 12 cases of recently radiated thyroids, and 15 cases of nonradiated thyroids were included. In the nonradiated and recently radiated thyroids, the mean frequency of allelic loss was 2.3%. In the thyroids from patients radiated as chi ...

Source: www.ncbi.nlm.nih.gov --- 7 hours ago
Related Articles Vascular endothelial growth factor in astroglioma stem cell biology and response to therapy. J Cell Mol Med. 2008 Jan-Feb;12(1):111-25 Authors: Knizetova P, Darling JL, Bartek J Malignant astrogliomas are among the most aggressive, highly vascular and infiltrating tumours bearing a dismal prognosis, mainly due to their resistance to current Radiation treatment and chemotherapy. Efforts to identify and target the mechanisms that underlie astroglioma resistance have recently focused on candidate cancer stem cells, their biological properties, interplay with their local microenvironment or 'niche', and their role in tumour progression and recurrence. Both paracrine and autocrine regulation of astroglioma cell behaviour by locally produced cytokines such as the vascular endothelial growth factor (VEGF) are emerging as key factors that determine astroglioma cell fate. Here, we review these recent rapid advances in astroglioma research, with emphasis on the significance of VEGF in astroglioma stem-like cell biology. Furthermore, we highlight the unique DNA Damage checkpoint properties of the CD133-marker-positive astroglioma stem-like cells, discuss their potential involvement in astroglioma radioresistance, and consider the implications of this new knowledge for designing combinatorial, more efficient therapeutic strategies. PMID: 18031298 [PubMed - indexed for MEDLINE] ...

Source: www.ncbi.nlm.nih.gov --- 13 days ago
Related Articles Gamma-H2AX - a novel biomarker for DNA double-strand breaks. In Vivo. 2008 May-Jun;22(3):305-9 Authors: Kuo LJ, Yang LX When DNA Damage, whether it is endogenous or exogenous, forms double stranded breaks (DSBs), it is always followed by the phosphorylation of the histone, H2AX. H2AX is a variant of the H2A protein family, which is a component of the histone octomer in nucleosomes. It is phosphorylated by kinases such as ataxia telangiectasia mutated (ATM) and ATM-Rad3-related (ATR) in the PI3K pathway. This newly phosphorylated protein, gamma-H2AX, is the first step in recruiting and localizing DNA repair proteins. DSBs can be induced by mechanisms such as ionizing Radiation or cytotoxic agents and subsequently, gamma-H2AX foci quickly form. These foci represent the DSBs in a 1:1 manner and can be used as a biomarker for Damage. An antibody can be raised against gamma-H2AX which can therefore be visualized by immunofluorescence through secondary antibodies. The detection and visualization of gamma-H2AX by flow cytometry allow the assessment of DNA Damage, related DNA Damage proteins and DNA repair. Gamma-H2AX also has other applications in the detection of genomic Damage caused by cytotoxic chemical agents and environmental and physical Damage, especially in the context of cancer treatment and therapy. PMID: 18610740 [PubMed - in process] ...

Source: www.ncbi.nlm.nih.gov --- 4 days ago
Related Articles Nutlin-3 radiosensitizes hypoxic prostate cancer cells independent of p53. Mol Cancer Ther. 2008 Apr;7(4):993-9 Authors: Supiot S, Hill RP, Bristow RG Nutlin-3 is a small-molecule inhibitor that acts to inhibit MDM2 binding to p53 and subsequent p53-dependent DNA Damage signaling. Whether Nutlin-3 alters cell toxicity following DNA Damage under oxic versus hypoxic conditions has not been studied. The potential radiosensitization (0-10 Gy) properties of Nutlin-3 (dose range, 2-10 micromol/L for up to 24 h) were investigated in vitro using three prostate cancer cell lines, 22RV1 [wild-type p53 (WTp53)], DU145 (mutated p53), and PC-3 (p53-null) under oxic (21% O(2)), hypoxic (0.2% O(2)), and anoxic (0% O(2)) conditions. As a single agent, Nutlin-3 (2-10 micromol/L) stabilized p53 and p21(WAF) levels and was toxic to WTp53-22RV1 cells (IC(50), 4.3 micromol/L) but had minimal toxicity toward p53-deficient cells (IC(50), >10 micromol/L). When combined with Radiation under oxic conditions, Nutlin-3 decreased clonogenic survival in all three cell lines: 22RV1 [sensitizing enhancement ratio (SER), 1.24], DU145 (SER, 1.27), and PC-3 (SER, 1.12). Anoxia induced p53 protein expression in 22RV1 cells and this was augmented by Nutlin-3 treatment. Furthermore, Nutlin-3 was more effective as a radiosensitizer under hypoxic conditions particularly in WTp53-expressing cells: 22RV1 (SER, 1.78), DU145 (SER, 1.31), and PC-3 (SER, 1.28). Th ...

Source: blog.wired.com --- 17 hours ago
Mustard on the moon? NASA scientists are suggesting that before sending humans back to the moon, we should launch plants there and watch them grow. Dr. Chris McKay, my former astrobiology mentor at NASA, and plant biologist Dr. Robert Ferl of the University of Florida, presented their plan at a meeting of lunar scientists at NASA Ames this week. The idea is simple: Fly a simple plant habitat to the moon. Bring along seeds (you don't have to care for them or feed them on the launch pad or the flight out). Germinate them inside your lunar plant-growth module on the surface and see how they cope with the low gravity, temperature and pressure as well as the high Radiation by monitoring their gene expression. You can even go a step further and add lunar soil to the chamber to monitor the toxicity of the soil or the content of the soil. Like the white mouse is for mammals, Arabidopsis thaliana (a member of the Mustard family) is the model organism for plants. It can go from seed to seed in six weeks, has a small, fully sequenced genome, can live under low-powered LED light, and has simple techniques for introducing fluorescent marker proteins into its genome. This allows the plant to be used as a highly sensitive bio-marker (indicator) for Radiation Damage or other stresses. You simply attach a Green Fluorescent Protein (GFP) to a protein known to be produced in response to a given condition or stress. Then when you look at the plant u ...

Source: ilp-www.mit.edu --- 23 days ago
We report the results of operation of Alcator C-Mod with all high-Z molybdenum Plasma Facing Component (PFC) surfaces. Without boron-coated PFCs energy confinement was poor (HJTER,89 1) due to high core molybdenum (nMo/neSO. 1%) and Radiation. After applying boron coatings, nMJn was reduced by a factor of 10-20 with H1TERJ9 approaching 2. Results of between-discharge boronization, localized at various major radii, point towards important molybdenum source regions being small, outside the divertor, and due to RF- sheath-rectification. Boronization also has a significant effect on the plasma startup phase lowering Zcff, Radiation, and lowering the runaway electron Damage. The requirement of low- Z coatings over at least a fraction of the Mo PFCs in C-Mod for best performance together with the larger than expected D retention in Mo, give impetus for further high-Z PFC investigations to better predict the performance of uncoated tungsten surfaces in ITER and beyond. ...