HGF/SF increases number of skin melanocytes but does not alter quality or quantity of follicular melanogenesis.

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Agnieszka Wolnicka-Glubisz

Full Text Available Melanins are an important factor determining the vulnerability of mammalian skin to UV radiation and thus to UV-induced skin cancers. Transgenic mice overexpressing hepatocyte growth factor/scatter factor (HGF/SF have extra-follicular dermal melanocytes, notably in the papillary upper dermis, and are susceptible to UV-induced melanoma. Pigmented HGF/SF neonatal mice are more susceptible than albino HGF/SF animals to UVA -induced melanoma, indicating an involvement of melanin in melanoma formation. This raises the question of the effect of transgenic HGF/SF on melanization. We developed a methodology to accurately quantitate both the production of melanin and the efficiency of melanogenesis in normal, and HGF/SF transgenic mice in vivo. Skin and hair shafts of 5 day old and adult (3 week old C57BL/6-HGF/SF and corresponding C57BL/6 wild type mice were investigated by electron paramagnetic resonance spectroscopy (EPR to quantitate melanin, by transmission electron microscopy (TEM for the presence of melanosomes, and by standard histology and by Western blotting and zymography to determine the expression and activity of melanogenesis-related proteins. Eumelanin but no phaeomelanin was detected in transgenic C57BL/6-HGF and C57BL/6 wild type mice. Transgenic HGF/SF overexpression did not change the type of melanin produced in the skin or hair, did not affect the terminal content of melanin production in standard samples of hair and did not influence hair cycle/morphogenesis-related changes in skin thickness. No melanocytes were found in the epidermis and no melanosomes were found in epidermal keratinocytes. HGF/SF transgenic mice thus lack the epidermal melanin UV-protection found in constitutively dark human skin. We conclude that melanocytes in the HGF/SF transgenic mouse, particularly in the papillary dermis, are vulnerable to UVA which interacts with eumelanin but not phaeomelanin to induce melanoma.

The Mechanism of Gefitinib Resistance Induced by Hepatocyte Growth Factor 
in Sensitive Non-small Cell Lung Cancer Cells in Vitro

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Xianglan XUAN

2013-01-01

Full Text Available Background and objective Previous studies have reported that Met might be related to gefitinib resistance in non-small cell lung cancer (NSCLC. The present study aims to explore the mechanism of hepatocyte growth factor (HGF-induced gefitinib resistance in different gene types of sensitive NSCLC in vitro. Methods The PC-9 and H292 cell lines were chosen and induced by HGF. The cell survival was measured using MTT assay, the cell cycle distribution was measured using PI assay, and cell apoptosis with an Annexin V-PE assay, respectively. The c-Met and p-Met protein expression was determined via Western blot analysis. Results Gefitinib inhibited the growth of PC-9 and H292 cells in a dose-dependent manner. The concentration-survival curves of both cell lines shifted to the right when induced with HGF. HGF did not affect PC-9 and H292 cell proliferation. The cell also had a higher cell survival rate when treated with HGF and gefitinib compared with that under gefitinib alone (P<0.05. The apoptotic rate and cell cycle progression showed no significant difference between the HG and G group (P>0.05. HGF stimulated Met phosphorylation in the PC-9 and H292 cells. Gefitinib inhibited the HGF-induced Met phosphorylation in PC-9 cells, but not in H292 cells. Conclusion HGF induces gefitinib resistance in PC-9 and H292 cells. HGF-induced Met phosphorylation may be an important mechanism of gefitinib resistance in sensitive NSCLC.

Role of Sphingosine Kinase 1 and S1P Transporter Spns2 in HGF-mediated Lamellipodia Formation in Lung Endothelium.

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Fu, Panfeng; Ebenezer, David L; Berdyshev, Evgeny V; Bronova, Irina A; Shaaya, Mark; Harijith, Anantha; Natarajan, Viswanathan

2016-12-30

Hepatocyte growth factor (HGF) signaling via c-Met is known to promote endothelial cell motility and angiogenesis. We have previously reported that HGF stimulates lamellipodia formation and motility of human lung microvascular endothelial cells (HLMVECs) via PI3K/Akt signal transduction and reactive oxygen species generation. Here, we report a role for HGF-induced intracellular sphingosine-1-phosphate (S1P) generation catalyzed by sphingosine kinase 1 (SphK1), S1P transporter, spinster homolog 2 (Spns2), and S1P receptor, S1P 1 , in lamellipodia formation and perhaps motility of HLMVECs. HGF stimulated SphK1 phosphorylation and enhanced intracellular S1P levels in HLMVECs, which was blocked by inhibition of SphK1. HGF enhanced co-localization of SphK1/p-SphK1 with actin/cortactin in lamellipodia and down-regulation or inhibition of SphK1 attenuated HGF-induced lamellipodia formation in HLMVECs. In addition, down-regulation of Spns2 also suppressed HGF-induced lamellipodia formation, suggesting a key role for inside-out S1P signaling. The HGF-mediated phosphorylation of SphK1 and its localization in lamellipodia was dependent on c-Met and ERK1/2 signaling, but not the PI3K/Akt pathway; however, blocking PI3K/Akt signaling attenuated HGF-mediated phosphorylation of Spns2. Down-regulation of S1P 1 , but not S1P 2 or S1P 3 , with specific siRNA attenuated HGF-induced lamellipodia formation. Further, HGF enhanced association of Spns2 with S1P 1 that was blocked by inhibiting SphK1 activity with PF-543. Moreover, HGF-induced migration of HLMVECs was attenuated by down-regulation of Spns2 . Taken together, these results suggest that HGF/c-Met-mediated lamellipodia formation, and perhaps motility is dependent on intracellular generation of S1P via activation and localization of SphK1 to cell periphery and Spns2-mediated extracellular transportation of S1P and its inside-out signaling via S1P 1 . © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Activated HGF-c-Met Axis in Head and Neck Cancer

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Levi Arnold

2017-12-01

Full Text Available Head and neck squamous cell carcinoma (HNSCC is a highly morbid disease. Recent developments including Food and Drug Administration (FDA approved molecular targeted agent’s pembrolizumab and cetuximab show promise but did not improve the five-year survival which is currently less than 40%. The hepatocyte growth factor receptor; also known as mesenchymal–epithelial transition factor (c-Met and its ligand hepatocyte growth factor (HGF are overexpressed in head and neck squamous cell carcinoma (HNSCC; and regulates tumor progression and response to therapy. The c-Met pathway has been shown to regulate many cellular processes such as cell proliferation, invasion, and angiogenesis. The c-Met pathway is involved in cross-talk, activation, and perpetuation of other signaling pathways, curbing the cogency of a blockade molecule on a single pathway. The receptor and its ligand act on several downstream effectors including phospholipase C gamma (PLCγ, cellular Src kinase (c-Src, phosphotidylinsitol-3-OH kinase (PI3K alpha serine/threonine-protein kinase (Akt, mitogen activate protein kinase (MAPK, and wingless-related integration site (Wnt pathways. They are also known to cross-talk with other receptors; namely epidermal growth factor receptor (EGFR and vascular endothelial growth factor receptor (VEGFR and specifically contribute to treatment resistance. Clinical trials targeting the c-Met axis in HNSCC have been undertaken because of significant preclinical work demonstrating a relationship between HGF/c-Met signaling and cancer cell survival. Here we focus on HGF/c-Met impact on cellular signaling in HNSCC to potentiate tumor growth and disrupt therapeutic efficacy. Herein we summarize the current understanding of HGF/c-Met signaling and its effects on HNSCC. The intertwining of c-Met signaling with other signaling pathways provides opportunities for more robust and specific therapies, leading to better clinical outcomes.

The Hepatocyte Growth Factor (HGF/Met Axis: A Neglected Target in the Treatment of Chronic Myeloproliferative Neoplasms?

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Marjorie Boissinot

2014-08-01

Full Text Available Met is the receptor of hepatocyte growth factor (HGF, a cytoprotective cytokine. Disturbing the equilibrium between Met and its ligand may lead to inappropriate cell survival, accumulation of genetic abnormalities and eventually, malignancy. Abnormal activation of the HGF/Met axis is established in solid tumours and in chronic haematological malignancies, including myeloma, acute myeloid leukaemia, chronic myelogenous leukaemia (CML, and myeloproliferative neoplasms (MPNs. The molecular mechanisms potentially responsible for the abnormal activation of HGF/Met pathways are described and discussed. Importantly, inCML and in MPNs, the production of HGF is independent of Bcr-Abl and JAK2V617F, the main molecular markers of these diseases. In vitro studies showed that blocking HGF/Met function with neutralizing antibodies or Met inhibitors significantly impairs the growth of JAK2V617F-mutated cells. With personalised medicine and curative treatment in view, blocking activation of HGF/Met could be a useful addition in the treatment of CML and MPNs for those patients with high HGF/MET expression not controlled by current treatments (Bcr-Abl inhibitors in CML; phlebotomy, hydroxurea, JAK inhibitors in MPNs.

The Hepatocyte Growth Factor (HGF)/Met Axis: A Neglected Target in the Treatment of Chronic Myeloproliferative Neoplasms?

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Boissinot, Marjorie [Translational Neuro-Oncology Group, Leeds Institute of Cancer and Pathology, University of Leeds, Level 5 Wellcome Trust Brenner Building, St James’s Hospital, Leeds LS9 7TF (United Kingdom); Vilaine, Mathias [Institute of Research on Cancer and Aging (IRCAN), CNRS-Inserm-UNS UMR 7284, U 1081, Centre A. Lacassagne, 33 Avenue Valombrose, Nice 06189 (France); Hermouet, Sylvie, E-mail: sylvie.hermouet@univ-nantes.fr [Centre Hospitalier Universitaire (CHU), Place Alexis Ricordeau, Nantes 44093 (France); Inserm UMR892, Centre de Recherche en Cancérologie Nantes-Angers, Institut de Recherche en Santé, Université de Nantes, 8 quai Moncousu, Nantes cedex 44007 (France)

2014-08-12

Met is the receptor of hepatocyte growth factor (HGF), a cytoprotective cytokine. Disturbing the equilibrium between Met and its ligand may lead to inappropriate cell survival, accumulation of genetic abnormalities and eventually, malignancy. Abnormal activation of the HGF/Met axis is established in solid tumours and in chronic haematological malignancies, including myeloma, acute myeloid leukaemia, chronic myelogenous leukaemia (CML), and myeloproliferative neoplasms (MPNs). The molecular mechanisms potentially responsible for the abnormal activation of HGF/Met pathways are described and discussed. Importantly, inCML and in MPNs, the production of HGF is independent of Bcr-Abl and JAK2V617F, the main molecular markers of these diseases. In vitro studies showed that blocking HGF/Met function with neutralizing antibodies or Met inhibitors significantly impairs the growth of JAK2V617F-mutated cells. With personalised medicine and curative treatment in view, blocking activation of HGF/Met could be a useful addition in the treatment of CML and MPNs for those patients with high HGF/MET expression not controlled by current treatments (Bcr-Abl inhibitors in CML; phlebotomy, hydroxurea, JAK inhibitors in MPNs)

HGF potentiates extracellular matrix-driven migration of human myoblasts: involvement of matrix metalloproteinases and MAPK/ERK pathway.

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González, Mariela Natacha; de Mello, Wallace; Butler-Browne, Gillian S; Silva-Barbosa, Suse Dayse; Mouly, Vincent; Savino, Wilson; Riederer, Ingo

2017-10-10

The hepatocyte growth factor (HGF) is required for the activation of muscle progenitor cells called satellite cells (SC), plays a role in the migration of proliferating SC (myoblasts), and is present as a soluble factor during muscle regeneration, along with extracellular matrix (ECM) molecules. In this study, we aimed at determining whether HGF is able to interact with ECM proteins, particularly laminin 111 and fibronectin, and to modulate human myoblast migration. We evaluated the expression of the HGF-receptor c-Met, laminin, and fibronectin receptors by immunoblotting, flow cytometry, or immunofluorescence and used Transwell assays to analyze myoblast migration on laminin 111 and fibronectin in the absence or presence of HGF. Zymography was used to check whether HGF could modulate the production of matrix metalloproteinases by human myoblasts, and the activation of MAPK/ERK pathways was evaluated by immunoblotting. We demonstrated that human myoblasts express c-Met, together with laminin and fibronectin receptors. We observed that human laminin 111 and fibronectin have a chemotactic effect on myoblast migration, and this was synergistically increased when low doses of HGF were added. We detected an increase in MMP-2 activity in myoblasts treated with HGF. Conversely, MMP-2 inhibition decreased the HGF-associated stimulation of cell migration triggered by laminin or fibronectin. HGF treatment also induced in human myoblasts activation of MAPK/ERK pathways, whose specific inhibition decreased the HGF-associated stimulus of cell migration triggered by laminin 111 or fibronectin. We demonstrate that HGF induces ERK phosphorylation and MMP production, thus stimulating human myoblast migration on ECM molecules. Conceptually, these data state that the mechanisms involved in the migration of human myoblasts comprise both soluble and insoluble moieties. This should be taken into account to optimize the design of therapeutic cell transplantation strategies by improving

Effect of gamma-irradiation on mouse pancreatic islet-allograft survival

International Nuclear Information System (INIS)

Kanai, T.; Porter, J.; Gotoh, M.; Monaco, A.P.; Maki, T.

1989-01-01

Elimination or inactivation of lymphoid tissue in the pancreatic islet preparation achieves prolongation of islet-allograft survival. In this study we examined the effect of gamma-irradiation on mouse islet-allograft survival. In a B6AF1 isograft model, irradiation up to 2400 rad did not induce deterioration of islet function over 200 days, but greater doses caused cessation of graft function between 83 and 186 days. When DBA/2 crude islets were transplanted into B6AF1 recipients, all nonirradiated allografts were acutely rejected. Marked prolongation of allograft survival was achieved by islet irradiation with doses between 800 and 12,000 rad. With higher doses, significant numbers of allografts survived beyond the controls, but many lost function between 78 and 180 days, with none surviving greater than 200 days. Irradiation with 16,000 rad caused acute radiation damage. Because most secondary islet allografts in recipient mice that lost primary islet-graft function between 84 and 195 days survived greater than 100 days, late functional loss was probably due to the radiation injury. Combined use of recipient treatment with cyclosporin A and graft irradiation (2400 rad) achieved prolongation of DBA/2 islets in B6AF1 mice

Irradiation effect on the apoptosis induction in the human cancer cell lines and the gingival fibroblast

International Nuclear Information System (INIS)

Park, Mu Soon; Lee, Sam Sun; Choi, Soon Chul; Park, Tae Won; You, Dong Soo

1998-01-01

The radiation-induced apoptosis was studied for two human cancer cell lines (KB cells, RPMI 2650 cells) and the human gingival fibroblast cell line (HGF-1 cells). The single irradiation of 2, 10, 20 Gy was done with 241.5 cGy/min dose rate using the 137 Cs MK cell irradiator. The cell were stained with propidium iodide and examined under the fluoro-microscope and assayed with the flow cytometry a day after irradiation. Also, the LDH assay was done to determine the amount of necrotic cells. The obtained results were as follows : 1. On the fluoro-microscope, many fragmented nuclei were detected in the KB, RPMI 2650, and HGF-1 cells after irradiation. 2. On the DNA content histogram obtained from the flow cytometry, the percentages of the pre-G1 peak of the control and 2, 10 and 20 Gy irradiation group were 4.5, 55.0, 52.3, and 66.6% on KB cells, 2.7, 3.3, 31.8, and 32.6% on RPMI 2650 cells and 2.8, 21.8, 30.4, and 40.2% on HGF-1 cells respectively. 3. The number of G1-stage cells was abruptly decreased after 2 Gy irradiation on KB cells and 10 Gy irradiation on RPMI 2650 cells, But there was a slight decrease without regard to irradiation dose on HGF-1 cells. 4. There was no significantly different absorbance in extracellular LDH assay along the experimental cell lines

The relationship between survival and mutagenesis in Escherichia coli after fractionated ultraviolet irradiation

International Nuclear Information System (INIS)

Dzidic, S.; Salaj-Smic, E.; Trgovcevic, Z.

1986-01-01

The relationship between survival and mutagenesis in Escherichia coli after fractionated ultraviolet (UV) irradiation was studied. The cells were incubated either in buffer or nutrient media. Regardless of incubation conditions, greater survival is observed after fractionated irradiation than after acute irradiation. When the cells are incubated in buffer, UV mutagenesis decreases with an increase in the number of dose fractions. However, when the cells are cultivated in nutrient media, the increased survival is coupled with the enhanced capacity for UV mutagenesis. The authors, therefore, assume that during incubation in nutrient media, fractionated irradiation leads to full and prolonged expression of all UV inducible (SOS) genes, including those required for mutagenesis. (Auth.)

Signal transduction and downregulation of C-MET in HGF stimulated low and highly metastatic human osteosarcoma cells

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Husmann, Knut, E-mail: khusmann@research.balgrist.ch [Laboratory for Orthopedic Research, Department of Orthopedics, Balgrist University Hospital, University of Zurich, Zurich (Switzerland); Ducommun, Pascal [Laboratory for Orthopedic Research, Department of Orthopedics, Balgrist University Hospital, University of Zurich, Zurich (Switzerland); Division of Plastic Surgery and Hand Surgery, Department of Surgery, University Hospital Zurich, Zurich (Switzerland); Sabile, Adam A.; Pedersen, Else-Marie; Born, Walter; Fuchs, Bruno [Laboratory for Orthopedic Research, Department of Orthopedics, Balgrist University Hospital, University of Zurich, Zurich (Switzerland)

2015-09-04

The poor outcome of osteosarcoma (OS), particularly in patients with metastatic disease and a five-year survival rate of only 20%, asks for more effective therapeutic strategies targeting malignancy-promoting mechanisms. Dysregulation of C-MET, its ligand hepatocyte growth factor (HGF) and the fusion oncogene product TPR-MET, first identified in human MNNG-HOS OS cells, have been described as cancer-causing factors in human cancers. Here, the expression of these molecules at the mRNA and the protein level and of HGF-stimulated signaling and downregulation of C-MET was compared in the parental low metastatic HOS and MG63 cell lines and the respective highly metastatic MNNG-HOS and 143B and the MG63-M6 and MG63-M8 sublines. Interestingly, expression of TPR-MET was only observed in MNNG-HOS cells. HGF stimulated the phosphorylation of Akt and Erk1/2 in all cell lines investigated, but phospho-Stat3 remained at basal levels. Downregulation of HGF-stimulated Akt and Erk1/2 phosphorylation was much faster in the HGF expressing MG63-M8 cells than in HOS cells. Degradation of HGF-activated C-MET occurred predominantly through the proteasomal and to a lesser extent the lysosomal pathway in the cell lines investigated. Thus, HGF-stimulated Akt and Erk1/2 signaling as well as proteasomal degradation of HGF activated C-MET are potential therapeutic targets in OS. - Highlights: • Expression of TPR-MET was only observed in MNNG-HOS cells. • HGF stimulated the phosphorylation of Akt and Erk1/2 but not of Stat3 in osteosarcoma cell lines. • Degradation of HGF-activated C-MET occurred predominantly through the proteasomal pathway.

Acceleration of astrocytic differentiation in neural stem cells surviving X-irradiation.

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Ozeki, Ayumi; Suzuki, Keiji; Suzuki, Masatoshi; Ozawa, Hiroki; Yamashita, Shunichi

2012-03-28

Neural stem cells (NSCs) are highly susceptible to DNA double-strand breaks; however, little is known about the effects of radiation in cells surviving radiation. Although the nestin-positive NSCs predominantly became glial fibrillary acidic protein (GFAP)-positive in differentiation-permissive medium, little or no cells were GFAP positive in proliferation-permissive medium. We found that more than half of the cells surviving X-rays became GFAP positive in proliferation-permissive medium. Moreover, localized irradiation stimulated differentiation of cells outside the irradiated area. These results indicate for the first time that ionizing radiation is able to stimulate astrocyte-specific differentiation of surviving NSCs, whose process is mediated both by the direct activation of nuclear factor-κB and by the indirect bystander effect induced by X-irradiation.

Enhanced antioxidant capacity of dental pulp-derived iPSC-differentiated hepatocytes and liver regeneration by injectable HGF-releasing hydrogel in fulminant hepatic failure.

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Chiang, Chih-Hung; Wu, Wai-Wah; Li, Hsin-Yang; Chien, Yueh; Sun, Cho-Chin; Peng, Chi-Hsien; Lin, Alex Tong-Long; Huang, Chi-Shuan; Lai, Ying-Hsiu; Chiou, Shih-Hwa; Hung, Shuen-Iu; Chang, Yuh-Lih; Lan, Yuan-Tzu; Liu, Dean-Mo; Chien, Chian-Shiu; Huo, Teh-Ia; Lee, Shou-Dong; Wang, Chien-Ying

2015-01-01

Acute hepatic failure (AHF) is a severe liver injury leading to sustained damage and complications. Induced pluripotent stem cells (iPSCs) may be an alternative option for the treatment of AHF. In this study, we reprogrammed human dental pulp-derived fibroblasts into iPSCs, which exhibited pluripotency and the capacity to differentiate into tridermal lineages, including hepatocyte-like cells (iPSC-Heps). These iPSC-Heps resembled human embryonic stem cell-derived hepatocyte-like cells in gene signature and hepatic markers/functions. To improve iPSC-Heps engraftment, we next developed an injectable carboxymethyl-hexanoyl chitosan hydrogel (CHC) with sustained hepatocyte growth factor (HGF) release (HGF-CHC) and investigated the hepatoprotective activity of HGF-CHC-delivered iPSC-Heps in vitro and in an immunocompromised AHF mouse model induced by thioacetamide (TAA). Intrahepatic delivery of HGF-CHC-iPSC-Heps reduced the TAA-induced hepatic necrotic area and rescued liver function and recipient viability. Compared with PBS-delivered iPSC-Heps, the HGF-CHC-delivered iPSC-Heps exhibited higher antioxidant and antiapoptotic activities that reduced hepatic necrotic area. Importantly, these HGF-CHC-mediated responses could be abolished by administering anti-HGF neutralizing antibodies. In conclusion, our findings demonstrated that HGF mediated the enhancement of iPSC-Hep antioxidant/antiapoptotic capacities and hepatoprotection and that HGF-CHC is as an excellent vehicle for iPSC-Hep engraftment in iPSC-based therapy against AHF.

Expression of hypoxia-inducible factor-1α and hepatocyte growth factor in development of fibrosis in the transplanted kidney

DEFF Research Database (Denmark)

Kellenberger, Terese; Marcussen, Niels; Nyengaard, Jens Randel

2014-01-01

Late renal graft loss is associated with interstitial fibrosis. Hypoxia-inducible factor-1α (HIF-1α) is thought to facilitate fibrosis through interaction with TGF-β1, while hepatocyte growth factor (HGF) may act antifibrotic in the kidney allograft. The aim of this study was to investigate...... transplantation, but an inverse significant correlation between the HGF expression and the fibrosis score 1 year after transplantation was shown. Even when adjusting for human leucocyte antigen mismatches, there was a significant relationship between fibrosis and HGF expression. Graft survival...... was not significantly correlated to HIF-1α or HGF at 1 year, although the trend was towards better graft survival with high HGF. HGF may have antifibrotic effects in human renal transplants. (Central.Denmark.Region.Committee number: 1-10-72-318-13)....

Hepatic Stellate Cell Coculture Enables Sorafenib Resistance in Huh7 Cells through HGF/c-Met/Akt and Jak2/Stat3 Pathways

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Weibo Chen

2014-01-01

Full Text Available Purpose. Tumor microenvironment confers drug resistance to kinase inhibitors by increasing RKT ligand levels that result in the activation of cell-survival signaling including PI3K and MAPK signals. We assessed whether HSC-LX2 coculture conferred sorafenib resistance in Huh7 and revealed the mechanism underlying the drug resistance. Experimental Design. The effect of LX2 on sorafenib resistance was determined by coculture system with Huh7 cells. The rescue function of LX2 supernatants was assessed by MTT assay and fluorescence microscopy. The underlying mechanism was tested by administration of pathway inhibitors and manifested by Western blotting. Results. LX2 coculture significantly induced sorafenib resistance in Huh7 by activating p-Akt that led to reactivation of p-ERK. LX2 secreted HGF into the culture medium that triggered drug resistance, and exogenous HGF could also induce sorafenib resistance. The inhibition of p-Akt blocked sorafenib resistance caused by LX2 coculture. Increased phosphorylation of Jak2 and Stat3 was also detected in LX2 cocultured Huh7 cells. The Jak inhibitor tofacitinib reversed sorafenib resistance by blocking Jak2 and Stat3 activation. The combined administration of sorafenib and p-Stat3 inhibitor S3I-201 augmented induced apoptosis even in the presence of sorafenib resistance. Conclusions. HSC-LX2 coculture induced sorafenib resistance in Huh7 through multiple pathways: HGF/c-Met/Akt pathway and Jak2/Stat3 pathway. A combined administration of sorafenib and S3I-201 was able to augment sorafenib-induced apoptosis even in the presence of LX2 coculture.

The influence of fractionation on cell survival and premature differentiation after carbon ion irradiation

International Nuclear Information System (INIS)

Wang Jufang; Li Renming; Guo Chuanling; Fournier, C.; K-Weyrather, W.

2008-01-01

To investigate the influence of fractionation on cell survival and radiation induced premature differentiation as markers for early and late effects after X-rays and carbon irradiation. Normal human fibroblasts NHDF, AG1522B and WI-38 were irradiated with 250 kV X-rays, or 266 MeV/u, 195 MeV/u and 11 MeV/u carbon ions. Cytotoxicity was measured by a clonogenic survival assay or by determination of the differentiation pattern. Experiments with high-energy carbon ions show that fractionation induced repair effects are similar to photon irradiation. The relative biological effective (RBE) 10 values for clonogenic survival are 1.3 and 1.6 for irradiation in one or two fractions for NHDF cells and around 1.2 for AG1522B cells regardless of the fractionation scheme. The RBE for a doubling of post mitotic fibroblasts (PMF) in the population is 1 for both single and two fractionated irradiation of NHDF cells. Using 11 MeV/u carbon ions, no repair effect can be seen in WI-38 cells. The RBE 10 for clonogenic survival is 3.2 for single irradiation and 4.9 for two fractionated irradiations. The RBE for a doubling of PMF is 3.1 and 5.0 for single and two fractionated irradiations, respectively. For both cell lines the effects of high-energy carbon ions representing the irradiation of the skin and the normal tissue in the entrance channel are similar to the effects of X-rays. The fractionation effects are maintained. For the lower energy, which is representative for the irradiation of the tumor region, RBE is enhanced for clonogenic survival as well as for premature terminal differentiation. Fractionation effects are not detectable. Consequently, the therapeutic ratio is significantly enhanced by fractionated irradiation with carbon ions. (author)

Antitumor bystander effect induced by radiation-inducible target gene therapy combined with α particle irradiation

International Nuclear Information System (INIS)

Liu Hui; Jin Chufeng; Wu Yican; Ge Shenfang; Wu Lijun; FDS Team

2012-01-01

In this work, we investigated the bystander effect of the tumor and normal cells surrounding the target region caused by radiation-inducible target gene therapy combined with α-particle irradiation. The receptor tumor cell A549 and normal cell MRC-5 were co-cultured with the donor cells irradiated to 0.5 Gy or the non-irradiated donor cells, and their survival and apoptosis fractions were evaluated. The results showed that the combined treatment of Ad-ET and particle irradiation could induce synergistic antitumor effect on A549 tumor cell, and the survival fraction of receptor cells co-cultured with the irradiated cells decreased by 6%, compared with receptor cells co-cultured with non-irradiated cells, and the apoptosis fraction increased in the same circumstance, but no difference was observed with the normal cells. This study demonstrates that Ad-ET combined with α-particle irradiation can significantly cause the bystander effect on neighboring tumor cells by inhibiting cell growth and inducing apoptosis, without obvious toxicity to normal cells. This suggests that combining radiation-inducible TRAIL gene therapy and irradiation may improve tumor treatment efficacy by specifically targeting tumor cells and even involving the neighboring tumor cells. (authors)

Regulation of HGF and SDF-1 expression by oral fibroblasts--implications for invasion of oral cancer.

Science.gov (United States)

Daly, Aisling J; McIlreavey, Leanne; Irwin, Chris R

2008-07-01

Invasion and metastasis of oral squamous cell carcinoma (OSCC) is dependent on signals received from stromal fibroblasts present in the surrounding connective tissue. The aim of this study was to investigate the regulation of expression of two important signaling molecules--HGF and SDF-1--by both stromal fibroblasts and their 'activated' form, myofibroblasts, and to determine the role of these two factors in stimulating OSCC cell invasion in vitro. Fibroblasts and myofibroblasts produced similar levels of HGF and SDF-1. IL-1alpha and OSCC cell conditioned medium both stimulated HGF and SDF-1 expression, while TGF-beta(1) inhibited production of each factor. Myofibroblast-derived conditioned medium stimulated OSCC cell invasion through matrigel. Blocking antibodies to both HGF and SDF-1 reduced the level of invasion. In fibroblast-free organotypic raft cultures, addition of HGF and SDF-1 stimulated OSCC cell invasion into the underlying collagen gel, although the pattern of invasion differed from that induced by fibroblasts. Fibroblast-derived HGF and SDF-1 appear to play central roles in the reciprocal interactions between OSCC cells and underlying stromal fibroblasts leading to the local invasion of oral cancer.

SNP analyses of growth factor genes EGF, TGFβ-1, and HGF reveal haplotypic association of EGF with autism

International Nuclear Information System (INIS)

Toyoda, Takao; Nakamura, Kazuhiko; Yamada, Kazuo; Thanseem, Ismail; Anitha, Ayyappan; Suda, Shiro; Tsujii, Masatsugu; Iwayama, Yoshimi; Hattori, Eiji; Toyota, Tomoko; Miyachi, Taishi; Iwata, Yasuhide; Suzuki, Katsuaki; Matsuzaki, Hideo; Kawai, Masayoshi; Sekine, Yoshimoto; Tsuchiya, Kenji; Sugihara, Gen-ichi; Ouchi, Yasuomi; Sugiyama, Toshiro; Takei, Nori; Yoshikawa, Takeo; Mori, Norio

2007-01-01

Autism is a pervasive neurodevelopmental disorder diagnosed in early childhood. Growth factors have been found to play a key role in the cellular differentiation and proliferation of the central and peripheral nervous systems. Epidermal growth factor (EGF) is detected in several regions of the developing and adult brain, where, it enhances the differentiation, maturation, and survival of a variety of neurons. Transforming growth factor-β (TGFβ) isoforms play an important role in neuronal survival, and the hepatocyte growth factor (HGF) has been shown to exhibit neurotrophic activity. We examined the association of EGF, TGFβ1, and HGF genes with autism, in a trio association study, using DNA samples from families recruited to the Autism Genetic Resource Exchange; 252 trios with a male offspring scored for autism were selected for the study. Transmission disequilibrium test revealed significant haplotypic association of EGF with autism. No significant SNP or haplotypic associations were observed for TGFβ1 or HGF. Given the role of EGF in brain and neuronal development, we suggest a possible role of EGF in the pathogenesis of autism

Hepatocyte transplantation improves early survival after partial hepatic resection and irradiation

International Nuclear Information System (INIS)

Guha, C.; Sharma, A.; Alfieri, A.; Guha, U.; Sokhi, R.; Gagandeep, S.; Gupta, S.; Vikram, B.; RoyChowdhury, J.

1997-01-01

Purpose: Radiation therapy (RT) is limited in its role as an adjuvant therapy of intrahepatic malignancies because of lower tolerance of human liver to irradiation (TD (5(5)) -TD (50(5)) ∼ 30-40 Gy). Although, surgical resection of primary or metastatic hepatic tumors has been shown to prolong survival, it is often limited by the presence of residual disease. RT could potentially improve survival of patients with positive surgical margins. However, radiation damage to the liver may be enhanced by hepatocellular proliferation induced by partial hepatic (PH) resection. We hypothesize that hepatocyte transplantation would be able to provide metabolic support and modulate the development of radiation-induced liver disease post-resection. The present study was designed to test the potential of hepatocyte transplantation in modifying the outcome of hepatocellular damage induced by PH and RT. Methods: Adult male Fischer 344 rats (Charles River) received hepatic irradiation of 50 Gy in a single fraction, after surgical exposure and shielding of the stomach and intestine, using a 320 MGC Philips orthovoltage unit. Immediately following irradiation, a two-third partial hepatectomy was performed. Four days post-radiation, the treatment group was injected with 5 x 10 6 syngeneic hepatocytes into the splenic pulp after a left subcostal incision, which allows homogeneous liver engraftment of the transplanted hepatocytes. Hematoxylin and eosin stains of liver biopsies, performed at various time points (3 days, 1, 2, 3 weeks or, anytime when animals died) were used for histologic evaluation. Time-adjusted survival was calculated from the date of irradiation by the product-limit Kaplan-Meier method, adjusting the denominator at every time point for the number of rats at risk. Results: Eight weeks after RT, 30% (n = 11) of the control animals (PH + 50 Gy) were alive compared to 100% (n = 9) of the transplant recipients (p <0.05). The median survival of the control group was 15

Sema4D, the ligand for Plexin B1, suppresses c-Met activation and migration and promotes melanocyte survival and growth.

Science.gov (United States)

Soong, Joanne; Chen, Yulin; Shustef, Elina M; Scott, Glynis A

2012-04-01

Semaphorins are secreted and membrane-bound proteins involved in neural pathfinding, organogenesis, and tumor progression, through Plexin and neuropilin receptors. We recently reported that Plexin B1, the Semaphorin 4D (Sema4D) receptor, is a tumor-suppressor protein for melanoma, which functions, in part, through inhibition of the oncogenic c-Met tyrosine kinase receptor. In this report, we show that Sema4D is a protective paracrine factor for normal human melanocyte survival in response to UV irradiation, and that it stimulates proliferation and regulates the activity of the c-Met receptor. c-Met receptor signaling stimulates melanocyte migration, partly through downregulation of the cell adhesion molecule E-cadherin. Sema4D suppressed activation of c-Met in response to its ligand, hepatocyte growth factor (HGF), and partially blocked the suppressive effects of HGF on E-cadherin expression in melanocytes and HGF-dependent migration. These data demonstrate a role for Plexin B1 in maintenance of melanocyte survival and proliferation in the skin, and suggest that Sema4D and Plexin B1 act cooperatively with HGF and c-Met to regulate c-Met-dependent effects in human melanocytes. Because our data show that Plexin B1 is profoundly downregulated by UVB in melanocytes, loss of Plexin B1 may accentuate HGF-dependent effects on melanocytes, including melanocyte migration.

The HGF strategy project

International Nuclear Information System (INIS)

Knebel, J.U.; Fellmoser, F.; Lefhalm, C.; Mack, K.; Pettan, C.; Piecha, H.; Konys, J.; Adelhelm, C.; Glasbrenner, H.; Muscher, H.; Novotny, J.; Voss, Z.; Wedemeyer, O.; Mueller, G.; Heinzel, A.; Schumacher, G.; Huber, R.; Zimmermann, F.; Groetzbach, G.; Dorr, B.; Carteciano, L.N.

2000-01-01

Within the Hermann von Helmholtz-Gemeinschaft Deutscher Forschungszentren (HGF) an HGF-Strategy Fund Project entitled 'Innovative Technologies to Reduce Radiotoxicity' is funded since October 1999. The objectives of this HGF-Strategy Fund Project is the development of new methods and technologies to design and manufacture thin-walled and highly thermally-loaded surfaces which are cooled by a corrosive heavy liquid metal (lead-bismuth eutectic). The result of this project will be the basic scientific-technical tool which allows the conception and the design of a European Demonstrator of an ADS system (cf. 32.23.05). The work performed at Forschungszentrum Karlsruhe is embedded in a broad European research and development programme on ADS systems. The project is divided in three sub-projects: Sub-Project 1: Thermalhydraulic Investigations, Sub-Project 2: Material Specific Investigations, Sub-Project 3: Oxygen Control System. This progress report gives a general description of the project and its envisaged objectives. As a selection of the results achieved, first, FLUTAN calculations for the COULI beam window design and, second, the oxygen control system for the KArlsruhe Lead LAboratory KALLA are described in detail. Finally, the design and status of KALLA is given. (orig.)

SNP analyses of growth factor genes EGF, TGF{beta}-1, and HGF reveal haplotypic association of EGF with autism

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Toyoda, Takao; Thanseem, Ismail; Kawai, Masayoshi; Sekine, Yoshimoto [Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Hamamatsu 431-3192 (Japan); Nakamura, Kazuhiko; Anitha, Ayyappan; Suda, Shiro [Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Hamamatsu 431-3192 (Japan); Yamada, Kazuo [Laboratory of Molecular Psychiatry, RIKEN Brain Science Institute, Saitama (Japan); Tsujii, Masatsugu [Faculty of Sociology, Chukyo University, Toyota, Aichi (Japan); [The Osaka-Hamamatsu Joint Research Center for Child Mental Development, Hamamatsu University School of Medicine, Hamamatsu (Japan); Iwayama, Yoshimi; Hattori, Eiji; Toyota, Tomoko; Yoshikawa, Takeo [Laboratory of Molecular Psychiatry, RIKEN Brain Science Institute, Saitama (Japan); Miyachi, Taishi; Tsuchiya, Kenji; Sugihara, Gen-ichi; Matsuzaki, Hideo [The Osaka-Hamamatsu Joint Research Center for Child Mental Development, Hamamatsu University School of Medicine, Hamamatsu (Japan); Iwata, Yasuhide; Suzuki, Katsuaki [Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Hamamatsu 431-3192 (Japan); Mori, Norio [Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Hamamatsu 431-3192 (Japan); [The Osaka-Hamamatsu Joint Research Center for Child Mental Development, Graduate School of Medicine, Osaka University (Japan); Ouchi, Yasuomi [The Osaka-Hamamatsu Joint Research Center for Child Mental Development, Hamamatsu University School of Medicine, Hamamatsu (Japan); [The Positron Medical Center, Hamamatsu Medical Center, Hamamatsu (Japan); Sugiyama, Toshiro [Aichi Children' s Health and Medical Center, Obu, Aichi (Japan); Takei, Nori [The Osaka-Hamamatsu Joint Research Center for Child Mental Development, Hamamatsu University School of Medicine, Hamamatsu (Japan)

2007-09-07

Autism is a pervasive neurodevelopmental disorder diagnosed in early childhood. Growth factors have been found to play a key role in the cellular differentiation and proliferation of the central and peripheral nervous systems. Epidermal growth factor (EGF) is detected in several regions of the developing and adult brain, where, it enhances the differentiation, maturation, and survival of a variety of neurons. Transforming growth factor-{beta} (TGF{beta}) isoforms play an important role in neuronal survival, and the hepatocyte growth factor (HGF) has been shown to exhibit neurotrophic activity. We examined the association of EGF, TGF{beta}1, and HGF genes with autism, in a trio association study, using DNA samples from families recruited to the Autism Genetic Resource Exchange; 252 trios with a male offspring scored for autism were selected for the study. Transmission disequilibrium test revealed significant haplotypic association of EGF with autism. No significant SNP or haplotypic associations were observed for TGF{beta}1 or HGF. Given the role of EGF in brain and neuronal development, we suggest a possible role of EGF in the pathogenesis of autism.

Regulation of HGF and c-MET Interaction in Normal Ovary and Ovarian Cancer.

Science.gov (United States)

Kwon, Youngjoo; Godwin, Andrew K

2017-04-01

Binding of hepatocyte growth factor (HGF) to the c-MET receptor has mitogenic, motogenic, and morphogenic effects on cells. The versatile biological effects of HGF and c-MET interactions make them important contributors to the development of malignant tumors. We and others have demonstrated a therapeutic value in targeting the interaction of c-MET and HGF in epithelial ovarian cancer (EOC). However, both HGF and c-MET are expressed in the normal ovary as well. Therefore, it is important to understand the differences in mechanisms that control HGF signaling activation and its functional role in the normal ovary and EOC. In the normal ovary, HGF signaling may be under hormonal regulation. During ovulation, HGF-converting proteases are secreted and the subsequent activation of HGF signaling enhances the proliferation of ovarian surface epithelium in order to replenish the area damaged due to expulsion of the ovum. In contrast, EOC cells that exhibit epithelial characteristics constitutively express both c-MET and HGF-converting proteases such as urokinase-type plasminogen activator. In EOC, mechanisms to control the activation of HGF signaling are absent since HGF is provided locally from the tissue microenvironment as well as remotely throughout the body. Potential incessant HGF signaling in EOC may lead to an increase in proliferation, invasion through the stroma, and migration to other tissues of cancer cells. Therefore, targeting the interaction of c-MET and HGF would be beneficial in treating EOC.

Flow cytometric determination of radiation-induced chromosome damage and its correlation with cell survival

International Nuclear Information System (INIS)

Welleweerd, J.; Wilder, M.E.; Carpenter, S.G.; Raju, M.R.

1984-01-01

Chinese hamster M3-1 cells were irradiated with several doses of x rays or α particles from 238 Pu. Propidium iodide-stained chromosome suspensions were prepared at different times after irradiation; cells were also assayed for survival. The DNA histograms of these chromosomes showed increased background counts with increased doses of radiation. This increase in background was cell-cycle dependent and was correlated with cell survival. The correlation between radiation-induced chromosome damage and cell survival was the same for X rays and α particles. Data are presented which indicate that flow cytometric analysis of chromosomes of irradiated cell populations can be a useful adjunct to classical cytogenic analysis of irradiation-induced chromosomal damage by virtue of its ability to express and measure chromosomal damage not seen by classical cytogenic methods

Exogenous HGF Bypasses the Effects of ErbB Inhibition on Tumor Cell Viability in Medulloblastoma Cell Lines.

Directory of Open Access Journals (Sweden)

Walderik W Zomerman

Full Text Available Recent clinical trials investigating receptor tyrosine kinase (RTK inhibitors showed a limited clinical response in medulloblastoma. The present study investigated the role of micro-environmental growth factors expressed in the brain, such as HGF and EGF, in relation to the effects of hepatocyte growth factor receptor (MET and epidermal growth factor receptor family (ErbB1-4 inhibition in medulloblastoma cell lines. Medulloblastoma cell lines were treated with tyrosine kinase inhibitors crizotinib or canertinib, targeting MET and ErbB1-4, respectively. Upon treatment, cells were stimulated with VEGF-A, PDGF-AB, HGF, FGF-2 or EGF. Subsequently, we measured cell viability and expression levels of growth factors and downstream signaling proteins. Addition of HGF or EGF phosphorylated MET or EGFR, respectively, and demonstrated phosphorylation of Akt and ERK1/2 as well as increased tumor cell viability. Crizotinib and canertinib both inhibited cell viability and phosphorylation of Akt and ERK1/2. Specifically targeting MET using shRNA's resulted in decreased cell viability. Interestingly, addition of HGF to canertinib significantly enhanced cell viability as well as phosphorylation of Akt and ERK1/2. The HGF-induced bypass of canertinib was reversed by addition of crizotinib. HGF protein was hardly released by medulloblastoma cells itself. Addition of canertinib did not affect RTK cell surface or growth factor expression levels. This manuscript points to the bypassing capacity of exogenous HGF in medulloblastoma cell lines. It might be of great interest to anticipate on these results in developing novel clinical trials with a combination of MET and EGFR inhibitors in medulloblastoma.

ARF1 and ARF6 regulate recycling of GRASP/Tamalin and the Rac1-GEF Dock180 during HGF-induced Rac1 activation.

Science.gov (United States)

Koubek, Emily J; Santy, Lorraine C

2018-05-04

Hepatocyte growth factor (HGF) is a potent signaling factor that acts on epithelial cells, causing them to dissociate and scatter. This migration is coordinated by a number of small GTPases, such as ARF6 and Rac1. Active ARF6 is required for HGF-stimulated migration and intracellular levels of ARF6-GTP and Rac1-GTP increase following HGF treatment. During migration, cross talk between ARF6 and Rac1 occurs through formation of a multi-protein complex containing the ARF-GEF cytohesin-2, the scaffolding protein GRASP/Tamalin, and the Rac1-GEF Dock180. Previously, the role of ARF6 in this process was unclear. We have now found that ARF6 and ARF1 regulate trafficking of GRASP and Dock180 to the plasma membrane following HGF treatment. Trafficking of GRASP and Dock180 is impaired by blocking ARF6-mediated recycling pathways and is required for HGF-stimulated Rac1 activation. Finally, HGF treatment stimulates association of GRASP and Dock180. Inhibition of ARF6 trafficking pathways traps GRASP and Dock180 as a complex in the cell.

Radioprotective effects of chlorogenic acid against mortality induced by gamma irradiation in mice

International Nuclear Information System (INIS)

Seyed Jalal Hosseinimehr; Amirhossein Ahmadi; Shahram Akhlaghpoor; Tehran University of Medical Sciences, Tehran

2007-01-01

Complete text of publication follows. The radioprotective effects of the naturally occurring compound chlorogenic acid has been investigated against mortality induced by gamma irradiation in mice. Chlorogenic acid administrated at single doses of 100, 200 and 400 mg/kg 1 and 24 h prior to lethal dose of gamma irradiation (8.5 Gy). At 30 days after treatment, the percentage of animal survival in each group was: control, 20%; 100 mg/kg, 20% and 15%; 200 mg/kg, 45% and 15%; 400 mg/kg, 25% and 35% for 1 h and 24 h treatment prior gamma irradiation, respectively. Percentage of survival increased in animal treated with this agent at 200 mg/kg at 1 h statistically compared with irradiated alone group. Other doses of chlorogenic acid have not showed any enhanced survival at 1 and 24 h before irradiation. Chlorogenic acid exhibited concentration-dependent activity on 1, 1-diphenyl 2-picrylhydrazyl free radical to show strong antioxidant activity. It appeared that chlorogenic acid with antioxidant activity reduced mortality induced by gamma irradiation.

Survival of irradiated mice treated with WR-151327, synthetic trehalose dicorynomycolate, or ofloxacin

Science.gov (United States)

Ledney, G. D.; Elliott, T. B.; Landauer, M. R.; Vigneulle, R. M.; Henderson, P. L.; Harding, R. A.; Tom, S. P.

1994-10-01

Spaceflight personnel need treatment options that would enhance survival from radiation and would not disrupt task performance. Doses of prophylactic or therapeutic agents known to induce significant short-term (30-day) survival with minimal behavioral (locomotor) changes were used for 180-day survival studies. In protection studies, groups of mice were treated with the phosphorothioate WR-151327 (200 mg/kg, 25% of the LD10) or the immunomodulator, synthetic trehalose dicorynomycolate (S-TDCM; 8 mg/kg), before lethal irradiation with reactor-generated fission neutrons and γ-rays (n/γ = 1) or 60Co γ-rays. In therapy studies, groups of mice received either S-TDCM, the antimicrobial ofloxacin, or S-TDCM plus ofloxacin after irradiation. For WR-151327 treated-mice, survival at 180 days for n/γ = 1 and γ-irradiated mice was 90% and 92%, respectively; for S-TDCM (protection), 57% and 78%, respectively; for S-TDCM (therapy), 20% and 25%, respectively; for ofloxacin, 38% and 5%, respectively; for S-TDCM combined with ofloxacin, 30% and 30%, respectively; and for saline, 8% and 5%, respectively. Ofloxacin or combined ofloxacin and S-TDCM increased survival from the gram-negative bacterial sepsis that predominated in n/γ = 1) irradiated mice. The efficacies of the treatments depended on radiation quality, treatment agent and its mode of use, and microflora of the host.

Effects of Adenovirus-Mediated Delivery of the Human Hepatocyte Growth Factor Gene in Experimental Radiation-Induced Heart Disease

International Nuclear Information System (INIS)

Hu Shunying; Chen Yundai; Li Libing; Chen Jinlong; Wu Bin; Zhou, Xiao; Zhi Guang; Li Qingfang; Wang Rongliang; Duan Haifeng; Guo Zikuan; Yang Yuefeng; Xiao Fengjun; Wang Hua; Wang Lisheng

2009-01-01

Purpose: Irradiation to the heart may lead to late cardiovascular complications. The purpose of this study was to investigate whether adenovirus-mediated delivery of the human hepatocyte growth factor gene could reduce post-irradiation damage of the rat heart and improve heart function. Methods and Materials: Twenty rats received single-dose irradiation of 20 Gy gamma ray locally to the heart and were randomized into two groups. Two weeks after irradiation, these two groups of rats received Ad-HGF or mock adenovirus vector intramyocardial injection, respectively. Another 10 rats served as sham-irradiated controls. At post-irradiation Day 120, myocardial perfusion was tested by myocardial contrast echocardiography with contrast agent injected intravenously. At post-irradiation Day 180, cardiac function was assessed using the Langendorff technique with an isolated working heart model, after which heart samples were collected for histological evaluation. Results: Myocardial blood flow was significantly improved in HGF-treated animals as measured by myocardial contrast echocardiography at post-irradiation Day 120 . At post-irradiation Day 180, cardiac function was significantly improved in the HGF group compared with mock vector group, as measured by left ventricular peak systolic pressure (58.80 ± 9.01 vs. 41.94 ± 6.65 mm Hg, p < 0.05), the maximum dP/dt (5634 ± 1303 vs. 1667 ± 304 mm Hg/s, p < 0.01), and the minimum dP/dt (3477 ± 1084 vs. 1566 ± 499 mm Hg/s, p < 0.05). Picrosirius red staining analysis also revealed a significant reduction of fibrosis in the HGF group. Conclusion: Based on the study findings, hepatocyte growth factor gene transfer can attenuate radiation-induced cardiac injury and can preserve cardiac function.

Study on DNA Damage Induced by Neon Beam Irradiation in Saccharomyces Cerevisiae

International Nuclear Information System (INIS)

Lu Dong; Li Wenjian; Wu Xin; Wang Jufang; Ma Shuang; Liu Qingfang; He Jinyu; Jing Xigang; Ding Nan; Dai Zhongying; Zhou Jianping

2010-01-01

Yeast strain Saccharomyces cerevisiae was irradiated with different doses of 85 MeV/u 20 Ne 10+ to investigate DNA damage induced by heavy ion beam in eukaryotic microorganism. The survival rate, DNA double strand breaks (DSBs) and DNA polymorphic were tested after irradiation. The results showed that there were substantial differences in DNA between the control and irradiated samples. At the dose of 40 Gy, the yeast cell survival rate approached 50%, DNA double-strand breaks were barely detectable, and significant DNA polymorphism was observed. The alcohol dehydrogenase II gene was amplified and sequenced. It was observed that base changes in the mutant were mainly transversions of T→G and T→C. It can be concluded that heavy ion beam irradiation can lead to change in single gene and may be an effective way to induce mutation.

Study on DNA Damage Induced by Neon Beam Irradiation in Saccharomyces Cerevisiae

Science.gov (United States)

Lu, Dong; Li, Wenjian; Wu, Xin; Wang, Jufang; Ma, Shuang; Liu, Qingfang; He, Jinyu; Jing, Xigang; Ding, Nan; Dai, Zhongying; Zhou, Jianping

2010-12-01

Yeast strain Saccharomyces cerevisiae was irradiated with different doses of 85 MeV/u 20Ne10+ to investigate DNA damage induced by heavy ion beam in eukaryotic microorganism. The survival rate, DNA double strand breaks (DSBs) and DNA polymorphic were tested after irradiation. The results showed that there were substantial differences in DNA between the control and irradiated samples. At the dose of 40 Gy, the yeast cell survival rate approached 50%, DNA double-strand breaks were barely detectable, and significant DNA polymorphism was observed. The alcohol dehydrogenase II gene was amplified and sequenced. It was observed that base changes in the mutant were mainly transversions of T→G and T→C. It can be concluded that heavy ion beam irradiation can lead to change in single gene and may be an effective way to induce mutation.

Human fibroblast strain with normal survival but abnormal postreplication repair after ultraviolet light irradiation

International Nuclear Information System (INIS)

Doniger, J.; Barrett, S.F.; Robbins, J.H.

1980-01-01

Postreplication repair has been studied in ultraviolet light (UV-irradiated) fibroblast strains derived from eight apparently normal control donors and seven xeroderma pigmentosum patients. One control donor strain had an intermediate defect in postreplication repair similar to that in excision-deficient xeroderma pigmentosum fibroblasts. However, unlike the xeroderma pigmentosum strains, this control donor strain had normal UV-induced unscheduled DNA synthesis and normal survival after irradiation with UV. This unique fibroblast strain should be useful in studies designed to elucidate the possible role of postreplication repair in UV-induced carcinogenesis and mutagenesis

Sublethal irradiation promotes invasiveness of neuroblastoma cells

International Nuclear Information System (INIS)

Schweigerer, Lothar; Rave-Fraenk, Margret; Schmidberger, Heinz; Hecht, Monica

2005-01-01

Neuroblastoma is the most frequent extracranial solid tumour of childhood. Despite multiple clinical efforts, clinical outcome has remained poor. Neuroblastoma is considered to be radiosensitive, but some clinical studies including the German trial NB90 failed to show a clinical benefit of radiation therapy. The mechanisms underlying this apparent discrepancy are still unclear. We have therefore investigated the effects of radiation on neuroblastoma cell behaviour in vitro. We show that sublethal doses of irradiation up-regulated the expression of the hepatocyte growth factor (HGF) and its receptor c-Met in some neuroblastoma cell lines. The increase in HGF/c-Met expression was correlated with enhanced invasiveness and activation of proteases degrading the extracellular matrix. Thus, irradiation at sublethal doses may promote the metastatic dissemination of neuroblastoma cells through activating the HGF/c-Met pathway and triggering matrix degradation

Enhanced cell survival and paracrine effects of mesenchymal stem cells overexpressing hepatocyte growth factor promote cardioprotection in myocardial infarction

International Nuclear Information System (INIS)

Zhao, Liyan; Liu, Xiaolin; Zhang, Yuelin; Liang, Xiaoting; Ding, Yue; Xu, Yan; Fang, Zhen; Zhang, Fengxiang

2016-01-01

Poor cell survival post transplantation compromises the therapeutic benefits of mesenchymal stem cells (MSCs) in myocardial infarction (MI). Hepatocyte growth factor (HGF) is an important cytokine for angiogenesis, anti-inflammation and anti-apoptosis. This study aimed to evaluate the cardioprotective effects of MSCs overexpressing HGF in a mouse model of MI. The apoptosis of umbilical cord-derived MSCs (UC-MSCs) and HGF-UC-MSCs under normoxic and hypoxic conditions was detected. The conditioned medium (CdM) of UC-MSCs and HGF-UC-MSCs under a hypoxic condition was harvested and its protective effect on neonatal cardiomyocytes (NCMs) exposed to a hypoxic challenge was examined. UC-MSCs and HGF-UC-MSCs were transplanted into the peri-infarct region in mice following MI and heart function assessed 4 weeks post transplantation. The apoptosis of HGF-UC-MSCs under hypoxic conditions was markedly decreased compared with that of UC-MSCs. NCMs treated with HGF-UC-MSC hypoxic CdM (HGF-UC-MSCs-hy-CdM) exhibited less cell apoptosis in response to hypoxic challenge than those treated with UC-MSC hypoxic CdM (UC-MSCs-hy-CdM). HGF-UC-MSCs-hy-CdM released the inhibited p-Akt and lowered the enhanced ratio of Bax/Bcl-2 induced by hypoxia in the NCMs. HGF-UC-MSCs-hy-CdM expressed higher levels of HGF, EGF, bFGF and VEGF than UC-MSCs-hy-CdM. Transplantation of HGF-UC-MSCs or UC-MSCs greatly improved heart function in the mouse model of MI. Compared with UC-MSCs, transplantation of HGF-UC-MSCs was associated with less cardiomyocyte apoptosis, enhanced angiogenesis and increased proliferation of cardiomyocytes. This study may provide a novel therapeutic strategy for MSC-based therapy in cardiovascular disease.

Enhanced cell survival and paracrine effects of mesenchymal stem cells overexpressing hepatocyte growth factor promote cardioprotection in myocardial infarction

Energy Technology Data Exchange (ETDEWEB)

Zhao, Liyan; Liu, Xiaolin [Section of Pacing and Electrophysiology, Division of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing (China); Zhang, Yuelin [Cardiology Division, Department of Medicine, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong (China); Liang, Xiaoting; Ding, Yue [Pudong District Clinical Translational Medical Research Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai (China); Xu, Yan; Fang, Zhen [Section of Pacing and Electrophysiology, Division of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing (China); Zhang, Fengxiang, E-mail: njzfx6@njmu.edu.cn [Section of Pacing and Electrophysiology, Division of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing (China)

2016-05-15

Poor cell survival post transplantation compromises the therapeutic benefits of mesenchymal stem cells (MSCs) in myocardial infarction (MI). Hepatocyte growth factor (HGF) is an important cytokine for angiogenesis, anti-inflammation and anti-apoptosis. This study aimed to evaluate the cardioprotective effects of MSCs overexpressing HGF in a mouse model of MI. The apoptosis of umbilical cord-derived MSCs (UC-MSCs) and HGF-UC-MSCs under normoxic and hypoxic conditions was detected. The conditioned medium (CdM) of UC-MSCs and HGF-UC-MSCs under a hypoxic condition was harvested and its protective effect on neonatal cardiomyocytes (NCMs) exposed to a hypoxic challenge was examined. UC-MSCs and HGF-UC-MSCs were transplanted into the peri-infarct region in mice following MI and heart function assessed 4 weeks post transplantation. The apoptosis of HGF-UC-MSCs under hypoxic conditions was markedly decreased compared with that of UC-MSCs. NCMs treated with HGF-UC-MSC hypoxic CdM (HGF-UC-MSCs-hy-CdM) exhibited less cell apoptosis in response to hypoxic challenge than those treated with UC-MSC hypoxic CdM (UC-MSCs-hy-CdM). HGF-UC-MSCs-hy-CdM released the inhibited p-Akt and lowered the enhanced ratio of Bax/Bcl-2 induced by hypoxia in the NCMs. HGF-UC-MSCs-hy-CdM expressed higher levels of HGF, EGF, bFGF and VEGF than UC-MSCs-hy-CdM. Transplantation of HGF-UC-MSCs or UC-MSCs greatly improved heart function in the mouse model of MI. Compared with UC-MSCs, transplantation of HGF-UC-MSCs was associated with less cardiomyocyte apoptosis, enhanced angiogenesis and increased proliferation of cardiomyocytes. This study may provide a novel therapeutic strategy for MSC-based therapy in cardiovascular disease.

Multiple regulatory mechanisms of hepatocyte growth factor expression in malignant cells with a short poly(dA) sequence in the HGF gene promoter.

Science.gov (United States)

Sakai, Kazuko; Takeda, Masayuki; Okamoto, Isamu; Nakagawa, Kazuhiko; Nishio, Kazuto

2015-01-01

Hepatocyte growth factor (HGF) expression is a poor prognostic factor in various types of cancer. Expression levels of HGF have been reported to be regulated by shorter poly(dA) sequences in the promoter region. In the present study, the poly(dA) mononucleotide tract in various types of human cancer cell lines was examined and compared with the HGF expression levels in those cells. Short deoxyadenosine repeat sequences were detected in five of the 55 cell lines used in the present study. The H69, IM95, CCK-81, Sui73 and H28 cells exhibited a truncated poly(dA) sequence in which the number of poly(dA) repeats was reduced by ≥5 bp. Two of the cell lines exhibited high HGF expression, determined by reverse transcription quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. The CCK-81, Sui73 and H28 cells with shorter poly(dA) sequences exhibited low HGF expression. The cause of the suppression of HGF expression in the CCK-81, Sui73 and H28 cells was clarified by two approaches, suppression by methylation and single nucleotide polymorphisms in the HGF gene. Exposure to 5-Aza-dC, an inhibitor of DNA methyltransferase 1, induced an increased expression of HGF in the CCK-81 cells, but not in the other cells. Single-nucleotide polymorphism (SNP) rs72525097 in intron 1 was detected in the Sui73 and H28 cells. Taken together, it was found that the defect of poly(dA) in the HGF promoter was present in various types of cancer, including lung, stomach, colorectal, pancreas and mesothelioma. The present study proposes the negative regulation mechanisms by methylation and SNP in intron 1 of HGF for HGF expression in cancer cells with short poly(dA).

Characterization of HGF/Met Signaling in Cell Lines Derived From Urothelial Carcinoma of the Bladder

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Lee, Young H. [Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Apolo, Andrea B. [Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Agarwal, Piyush K.; Bottaro, Donald P., E-mail: dbottaro@helix.nih.gov [Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States)

2014-11-25

There is mounting evidence of oncogenic hepatocyte growth factor (HGF)/Met signaling in urothelial carcinoma (UC) of the bladder. The effects of three kinase inhibitors, cabozantinib, crizotinib and EMD1214063, on HGF-driven signaling and cell growth, invasion and tumorigenicity were analyzed in cultured UC cell lines. SW780 xenograft growth in SCID and human HGF knock-in SCID (hHGF/SCID) mice treated with cabozantinib or vehicle, as well as tumor levels of Met and pMet, were also determined. Met content was robust in most UC-derived cell lines. Basal pMet content and effector activation state in quiescent cells were low, but significantly enhanced by added HGF, as were cell invasion, proliferation and anchorage independent growth. These HGF-driven effects were reversed by Met inhibitor treatment. Tumor xenograft growth was significantly higher in hHGF/SCID mice vs. SCID mice and significantly inhibited by cabozantinib, as was tumor phospho-Met content. These studies indicate the prevalence and functionality of the HGF/Met signaling pathway in UC cells, suggest that paracrine HGF may contribute to UC tumor growth and progression, and that support further preclinical investigation of Met inhibitors for the treatment of UC is warranted.

STI571 (Gleevec) improves tumor growth delay and survival in irradiated mouse models of glioblastoma

International Nuclear Information System (INIS)

Geng Ling; Shinohara, Eric T.; Kim, Dong; Tan Jiahuai; Osusky, Kate; Shyr, Yu; Hallahan, Dennis E.

2006-01-01

Purpose: Glioblastoma multiforme (GBM) is a devastating brain neoplasm that is essentially incurable. Although radiation therapy prolongs survival, GBMs progress within areas of irradiation. Recent studies in invertebrates have shown that STI571 (Gleevec; Novartis, East Hanover, NJ) enhances the cytotoxicity of ionizing radiation. In the present study, the effectiveness of STI571 in combination with radiation was studied in mouse models of GBM. Methods and Materials: Murine GL261 and human D54 GBM cell lines formed tumors in brains and hind limbs of C57BL6 and nude mice, respectively. GL261 and D54 cells were treated with 5 μmol/L of STI571 for 1 h and/or irradiated with 3 Gy. Protein was analyzed by Western immunoblots probed with antibodies to caspase 3, cleaved caspase 3, phospho-Akt, Akt, and platelet-derived growth factor receptor (PDGFR) α and β. Tumor volumes were assessed in mice bearing GL261 or D54 tumors treated with 21 Gy administered in seven fractionated doses. Histologic sections from STI571-treated mice were stained with phospho-Akt and phospho-PDGFR β antibodies. Kaplan-Meier survival curves were used to study the response of mice bearing intracranial implants of GL261. Results: STI571 penetrated the blood-brain barrier, which resulted in a reduction in phospho-PDGFR in GBM. STI571-induced apoptosis in GBM was significantly enhanced by irradiation. STI571 combined with irradiation induced caspase 3 cleavage in GBM cells. Glioblastoma multiforme response to therapy correlated with an increase in tumor growth delay and survival when STI571 was administered in conjunction with daily irradiation. Conclusion: These findings suggest that STI571 has the potential to augment radiotherapy and thereby improve median survival

The potential roles of hepatocyte growth factor (HGF-MET pathway inhibitors in cancer treatment

Directory of Open Access Journals (Sweden)

Parikh RA

2014-06-01

Full Text Available Rahul A Parikh,1 Peng Wang,2 Jan H Beumer,3 Edward Chu,1 Leonard J Appleman11Division of Hematology-Oncology, University of Pittsburgh School of Medicine, Cancer Therapeutics Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA; 2Division of Medical Oncology, University of Kentucky College of Medicine, Markey Cancer Center, Lexington, KY, USA; 3University of Pittsburgh School of Pharmacy, Cancer Therapeutics Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USAAbstract: MET is located on chromosome 7q31 and is a proto-oncogene that encodes for hepatocyte growth factor (HGF receptor, a member of the receptor tyrosine kinase (RTK family. HGF, also known as scatter factor (SF, is the only known ligand for MET. MET is a master regulator of cell growth and division (mitogenesis, mobility (motogenesis, and differentiation (morphogenesis; it plays an important role in normal development and tissue regeneration. The HGF-MET axis is frequently dysregulated in cancer by MET gene amplification, translocation, and mutation, or by MET or HGF protein overexpression. MET dysregulation is associated with an increased propensity for metastatic disease and poor overall prognosis across multiple tumor types. Targeting the dysregulated HGF-MET pathway is an area of active research; a number of monoclonal antibodies to HGF and MET, as well as small molecule inhibitors of MET, are under development. This review summarizes the key biological features of the HGF-MET axis, its dysregulation in cancer, and the therapeutic agents targeting the HGF-MET axis, which are in development.Keywords: MET inhibitor, HGF inhibitor, cancer

Umbilical Cord-derived Mesenchymal Stem Cells Instruct Monocytes Towards an IL10-producing Phenotype by Secreting IL6 and HGF.

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Deng, Yinan; Zhang, Yingcai; Ye, Linsen; Zhang, Tong; Cheng, Jintao; Chen, Guihua; Zhang, Qi; Yang, Yang

2016-12-05

Human UC-MSCs are regarded as an attractive alternative to BM-MSCs for clinical applications due to their easy preparation, higher proliferation and lower immunogenicity. However, the mechanisms underlying immune suppression by UC-MSCs are still unclear. We studied the mechanism of inhibition by UC-MSCs during the differentiation of monocytes into DCs and focused on the specific source and the role of the involved cytokines. We found that UC-MSCs suppressed monocyte differentiation into DCs and instructed monocytes towards other cell types, with clear decreases in the expression of co-stimulatory molecules, in the secretion of inflammatory factors and in allostimulatory capacity. IL6, HGF and IL10 might be involved in this process because they were detected at higher levels in a coculture system. UC-MSCs produce IL-6 and HGF, and neutralization of IL-6 and HGF reversed the suppressive effect of UC-MSCs. IL10 was not produced by UC-MSCs but was exclusively produced by monocytes after exposure to UC-MSCs, IL-6 or HGF. In summary, we found that the UC-MSC-mediated inhibitory effect was dependent on IL6 and HGF secreted by UC-MSCs and that this effect induced monocyte-derived cells to produce IL10, which might indirectly strengthen the suppressive effect of UC-MSCs.

Adipocytes enhance murine pancreatic cancer growth via a hepatocyte growth factor (HGF)-mediated mechanism.

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Ziegler, Kathryn M; Considine, Robert V; True, Eben; Swartz-Basile, Deborah A; Pitt, Henry A; Zyromski, Nicholas J

2016-04-01

Obesity accelerates the development and progression of pancreatic cancer, though the mechanisms underlying this association are unclear. Adipocytes are biologically active, producing factors such as hepatocyte growth factor (HGF) that may influence tumor progression. We therefore sought to test the hypothesis that adipocyte-secreted factors including HGF accelerate pancreatic cancer cell proliferation. Murine pancreatic cancer cells (Pan02 and TGP-47) were grown in a) conditioned medium (CM) from murine F442A preadipocytes, b) HGF-knockdown preadipocyte CM, c) recombinant murine HGF at increasing doses, and d) CM plus HGF-receptor (c-met) inhibitor. Cell proliferation was measured using the MTT assay. ANOVA and t-test were applied; p TGP-47 cell proliferation relative to control (59 ± 12% and 34 ± 12%, p TGP-47 cells remained unchanged. Recombinant HGF dose-dependently increased Pan02, but not TGP-47, proliferation (p TGP-47 cells. These experiments demonstrate that adipocyte-derived factors accelerate murine pancreatic cancer proliferation. In the case of Pan02 cells, HGF is responsible, in part, for this proliferation. Copyright © 2016 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.

Hepatocyte growth factor promotes long-term survival and axonal regeneration of retinal ganglion cells after optic nerve injury: comparison with CNTF and BDNF.

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Wong, Wai-Kai; Cheung, Anny Wan-Suen; Yu, Sau-Wai; Sha, Ou; Cho, Eric Yu Pang

2014-10-01

Different trophic factors are known to promote retinal ganglion cell survival and regeneration, but each had their own limitations. We report that hepatocyte growth factor (HGF) confers distinct advantages in supporting ganglion cell survival and axonal regeneration, when compared to two well-established trophic factors ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF). Ganglion cells in adult hamster were injured by cutting the optic nerve. HGF, CNTF, or BDNF was injected at different dosages intravitreally after injury. Ganglion cell survival was quantified at 7, 14, or 28 days postinjury. Peripheral nerve (PN) grafting to the cut optic nerve of the growth factor-injected eye was performed either immediately after injury or delayed until 7 days post-injury. Expression of heat-shock protein 27 and changes in microglia numbers were quantified in different growth factor groups. The cellular distribution of c-Met in the retina was examined by anti-c-Met immunostaining. Hepatocyte Growth Factor (HGF) was equally potent as BDNF in promoting short-term survival (up to 14 days post-injury) and also supported survival at 28 days post-injury when ganglion cells treated by CNTF or BDNF failed to be sustained. When grafting was performed without delay, HGF stimulated twice the number of axons to regenerate compared with control but was less potent than CNTF. However, in PN grafting delayed for 7 days after optic nerve injury, HGF maintained a better propensity of ganglion cells to regenerate than CNTF. Unlike CNTF, HGF application did not increase HSP27 expression in ganglion cells. Microglia proliferation was prolonged in HGF-treated retinas compared with CNTF or BDNF. C-Met was localized to both ganglion cells and Muller cells, suggesting HGF could be neuroprotective via interacting with both neurons and glia. Compared with CNTF or BDNF, HGF is advantageous in sustaining long-term ganglion cell survival and their propensity to respond to

Microfluidic wound-healing assay to assess the regenerative effect of HGF on wounded alveolar epithelium.

Science.gov (United States)

Felder, Marcel; Sallin, Pauline; Barbe, Laurent; Haenni, Beat; Gazdhar, Amiq; Geiser, Thomas; Guenat, Olivier

2012-02-07

We present a microfluidic epithelial wound-healing assay that allows characterization of the effect of hepatocyte growth factor (HGF) on the regeneration of alveolar epithelium using a flow-focusing technique to create a regular wound in the epithelial monolayer. The phenotype of the epithelial cell was characterized using immunostaining for tight junction (TJ) proteins and transmission electron micrographs (TEMs) of cells cultured in the microfluidic system, a technique that is reported here for the first time. We demonstrate that alveolar epithelial cells cultured in a microfluidic environment preserve their phenotype before and after wounding. In addition, we report a wound-healing benefit induced by addition of HGF to the cell culture medium (19.2 vs. 13.5 μm h(-1) healing rate).

Irradiation-Induced Nanostructures

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Birtcher, R.C.; Ewing, R.C.; Matzke, Hj.; Meldrum, A.; Newcomer, P.P.; Wang, L.M.; Wang, S.X.; Weber, W.J.

1999-08-09

This paper summarizes the results of the studies of the irradiation-induced formation of nanostructures, where the injected interstitials from the source of irradiation are not major components of the nanophase. This phenomena has been observed by in situ transmission electron microscopy (TEM) in a number of intermetallic compounds and ceramics during high-energy electron or ion irradiations when the ions completely penetrate through the specimen. Beginning with single crystals, electron or ion irradiation in a certain temperature range may result in nanostructures composed of amorphous domains and nanocrystals with either the original composition and crystal structure or new nanophases formed by decomposition of the target material. The phenomenon has also been observed in natural materials which have suffered irradiation from the decay of constituent radioactive elements and in nuclear reactor fuels which have been irradiated by fission neutrons and other fission products. The mechanisms involved in the process of this nanophase formation are discussed in terms of the evolution of displacement cascades, radiation-induced defect accumulation, radiation-induced segregation and phase decomposition, as well as the competition between irradiation-induced amorphization and recrystallization.

Survivin and chromosome instability induced by X-irradiation

International Nuclear Information System (INIS)

Shen Bo; Ju Guizhi; Liu Yang

2006-01-01

Objective: To explore the biological effect of survivin on chromosome instability induced by X-ray irradiation. Methods: Immunocytochemistry was used to detect the expression of sutvivin in HeLa cells. Carrier pSUPER-SVV was transfected into HeLa cells to interfere the expression of survivin. Flow cytometry assay was applied to detect the occurrence of polyploid at 0 h, 4 h, 12 h, and 48 h after the HeLa cells transfected with pSUPER-SVV and irradiated with 4 Gy X-rays irradiation, and compared with the group irradiated with 4 Gy X-rays but no transfection. Results: The expression of survivin was down-regulated by transfecting with small hair RNA, its depression rate was estimated to be about 32.16% at 48 h after transfection. The occurrence of polyploid giant cells was higher in the 4 Gy X-ray irradiated group at 48 h after the irradiation than the control groups (P<0.001). Being expression of survivin interfered, the occurrence at 12 h or 48 h after irradiation, however, was about two times higher than that in the control group. Conclusion: X-ray irradiation can induce chromosome instability in HeLa cells and the effect could be enhanced by interfering the expression of surviving. It was suggested that survivin plays an important role in maintaining the stability of chromosome. (authors)

Survival patterns and hemopathological responses of dogs under continuous gamma irradiation

International Nuclear Information System (INIS)

Seed, T.M.; Fritz, T.E.; Tolle, D.V.; Poole, C.M.; Lombard, L.S.; Doyle, D.E.; Kaspar, L.V.; Cullen, S.M.; Carnes, B.A.

1983-01-01

Survival curves were constructed and analyzed relative to contributing hematopathological responses for groups of beagles exposed continuously for duration of life to low daily doses of whole body 60 Co gamma irradiation (27.3 rads/day to 4 rads/day). The survival curves versus time were progressively displaced toward longer survival as rates of exposure were reduced from the relatively high dose rate of 27.3 rads/day to the low dose rate of 4.0 rads/day. Average survival times increased from 57 days at 27.3 rads/day to 1830 days at 4.0 rads/day, representing fractional increased life-spans from 1.5% to 50.8%, respectively. Survival curves versus total dose were markedly displaced along the cumulative radiation dose axis at the extreme dose rates (i.e., 27.3 and 4.0 rads/day), but not at the intermediate dose rates (i.e., 13.4 and 7.9 rads/day) in which the upper linear portions of the survival curves are superimposed. From these dose-dependent survival curves, LD 50 values for whole body gamma irradiation, delivered chronically at 27.3, 13.4, 7.9, and 4.0 rads per day were estimated to be 1442, 2124, 2039, and 7161 rads, respectively. Both time- and dose-dependent survival curves for the intermediate dose rates, in contrast to the extreme dose rates, exhibited pronounced transitions in the lethality rate below the 50% survival level. These lethality rate transitions occurred at approx. 2500 rads of accumulated dose and were attributed to a shift in the spectrum of developing hematopathologies: namely, from a predominance of the acutely ablative radiation-induced lymphohematopoietic syndromes (i.e., septicemias and aplastic anemias) to a predominance of the late arising hematopoietic neoplasias (myelogenous leukemia and related myeloproliferative disorders)

Decreased survival of the λ15 bacteriophage induced by UV-365 nanometers in Escherichia coli

International Nuclear Information System (INIS)

Luca, M.E.M. de.

1989-01-01

The results of our investigation showed a new effect (not yet described in the current literature) of the UV-365 nm, verified when the bacteria E. coli was irradiated with this wavelenght and then infected with bacteriophage irradiated with short UV (254 nm). In these conditions we observed a decrease in the phage survival. This phenomenon was called Decreased Survival of the Bacteriophage (DSB). We were able to show that DSB was only induced in bacteria irradiated with UV-365 nm, proficient in recombination repair and owning 4-thiouridine in their tRNA. For the induction of DSB it is necessary to promote damage in the bacteriophage through UVA and UVB. It seems that DSB and SOS are antagonistic since DSB is able to suppress the mutation induced by SOS. (author)

The (PrS/HGF-pDNA) multilayer films for gene-eluting stent coating: Gene-protecting, anticoagulation, antibacterial properties, and in vivo antirestenosis evaluation.

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Chang, Hao; Ren, Ke-feng; Zhang, He; Wang, Jin-lei; Wang, Bai-liang; Ji, Jian

2015-02-01

Vascular gene-eluting stents (GES) is a promising strategy for treatment of cardiovascular disease. Very recently, we have proved that the (protamine sulfate/plasmid DNA encoding hepatocyte growth factor) (PrS/HGF-pDNA) multilayer can serve as a powerful tool for enhancing competitiveness of endothelial cell over smooth muscle cell, which opens perspectives for the regulation of intercellular competitiveness in the field of interventional therapy. However, before the gene multilayer films could be used in vascular stents for real clinical application, the preservation of gene bioactivity during the industrial sterilization and the hemocompatibility of film should be taken into account. Actually, both are long been ignored issues in the field of gene coating for GES. In this study, we demonstrate that the (PrS/HGF-pDNA) multilayer film exhibits the good gene-protecting abilities, which is confirmed by using the industrial sterilizations (gamma irradiation and ethylene oxide) and a routine storage condition (dry state at 4°C for 30 days). Furthermore, hemocompatible measurements (such as platelet adhesion and whole blood coagulation) and antibacterial assays (bacteria adhesion and growth inhibition) indicate the good anticoagulation and antibacterial properties of the (PrS/HGF-pDNA) multilayer film. The in vivo preliminary data of angiography and histological analysis suggest that the (PrS/HGF-pDNA) multilayer coated stent can reduce the in-stent restenosis. This work reveals that the (PrS/HGF-pDNA) multilayer film could be a promising candidate as coating for GES, which is of great potential in future clinic application. © 2014 Wiley Periodicals, Inc.

Umbilical Cord-derived Mesenchymal Stem Cells Instruct Monocytes Towards an IL10-producing Phenotype by Secreting IL6 and HGF

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Deng, Yinan; Zhang, Yingcai; Ye, Linsen; Zhang, Tong; Cheng, Jintao; Chen, Guihua; Zhang, Qi; Yang, Yang

2016-01-01

Human UC-MSCs are regarded as an attractive alternative to BM-MSCs for clinical applications due to their easy preparation, higher proliferation and lower immunogenicity. However, the mechanisms underlying immune suppression by UC-MSCs are still unclear. We studied the mechanism of inhibition by UC-MSCs during the differentiation of monocytes into DCs and focused on the specific source and the role of the involved cytokines. We found that UC-MSCs suppressed monocyte differentiation into DCs and instructed monocytes towards other cell types, with clear decreases in the expression of co-stimulatory molecules, in the secretion of inflammatory factors and in allostimulatory capacity. IL6, HGF and IL10 might be involved in this process because they were detected at higher levels in a coculture system. UC-MSCs produce IL-6 and HGF, and neutralization of IL-6 and HGF reversed the suppressive effect of UC-MSCs. IL10 was not produced by UC-MSCs but was exclusively produced by monocytes after exposure to UC-MSCs, IL-6 or HGF. In summary, we found that the UC-MSC-mediated inhibitory effect was dependent on IL6 and HGF secreted by UC-MSCs and that this effect induced monocyte-derived cells to produce IL10, which might indirectly strengthen the suppressive effect of UC-MSCs. PMID:27917866

HGF is released from buccal fibroblasts after smokeless tobacco stimulation

DEFF Research Database (Denmark)

Dabelsteen, S; Christensen, S; Gron, B

2005-01-01

on exposure time and on concentration of the tobacco extract. High concentration increased production of HGF 4-fold. KGF production was doubled when high concentration of tobacco was used, low concentration did not stimulate cells. GM-CSF production was low in both stimulated and non-stimulated cells......To investigate the effect of smokeless tobacco (ST) on (1) HGF, KGF and GM-CSF expression by buccal fibroblasts and (2) on keratinocyte and fibroblast proliferation. Buccal fibroblasts were stimulated with different concentrations of ST extracts in a double dilution from 0.50% w/v to 0.03% w....... Keratinocytes and fibroblasts showed no increase in proliferation after stimulation with increased concentrations of ST. The results suggest that HGF and KGF may play an important role as a paracrine growth factor in epithelial hyperplasia in ST lesions....

Clinical and prognostic value of the C-Met/HGF signaling pathway in cervical cancer.

Science.gov (United States)

Boromand, Nadia; Hasanzadeh, Malihe; ShahidSales, Soodabeh; Farazestanian, Marjaneh; Gharib, Masoumeh; Fiuji, Hamid; Behboodi, Negin; Ghobadi, Niloofar; Hassanian, Seyed Mahdi; Ferns, Gordon A; Avan, Amir

2018-06-01

Aberrant activation of the HGF/c-Met signalling pathway is reported to be associated with cell proliferation, progression, and metastasis features of several tumor types, including cervical cancer, suggesting that it may be of potential value as a novel therapeutic target. Furthermore, HPV-positive patients had a higher serum level of HGF or c-Met protein, compared with HPV-negative patients. c-Met or HGF overexpression in lesions of cervical cancer is reported to be related to a poorer prognosis, and hence this may be of value as a prognostic and predictive biomarker. Several approaches have been developed for targeting HGF and/or c-Met. One of these is crizotinib (a dual c-Met/ALK inhibitor). This has been approved by FDA for the treatment of lung-cancer. Further investigations are required to evaluate and optimize the use of c-Met inhibitors in cervical cancer or parallel targeting signalling pathway associated/activated via MET/HGF pathway. The main aim of current review was to give an overview of the potential of the c-Met/HGF pathway as a prognostic, or predictive biomarker in cervical cancer. © 2017 Wiley Periodicals, Inc.

Additive effects of 5-Aza-2'-deoxycytidine and irradiation on clonogenic survival of human medulloblastoma cell lines

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Patties, Ina; Jahns, Jutta; Kortmann, Rolf-Dieter; Glasow, Annegret [Dept. of Radiotherapy and Radiooncology, Universitaetsklinikum Leipzig AoeR (Germany); Hildebrandt, Guido [Dept. of Radiotherapy and Radiooncology, Universitaetsklinikum Leipzig AoeR (Germany); Dept. of Radiotherapy, Univ. of Rostock (Germany)

2009-05-15

Background and purpose: in recent years, epigenetic modulators were introduced into tumor therapy. Here, the authors investigated the antitumor effect of 5-aza-2'-deoxycytidine-(5-aza-dC-)induced demethylation combined with irradiation on human medulloblastoma (MB) cells, which form the most common malignant brain tumor in children. Material and methods: three MB cell lines were treated with 5-aza-dC in a low-dose (0.1 {mu}M, 6 days) or high-dose (3/5 {mu}M, 3 days) setting and irradiated with 2, 4, 6, or 8 Gy single dose on an X-ray unit. Methylation status and mRNA expression of three candidate genes were analyzed by methylation-specific PCR (polymerase chain reaction) and quantitative real-time RT-PCR. Cell survival and mortality were determined by trypan blue exclusion test. Proliferation was analyzed by BrdU incorporation assay, and long-term cell survival was assessed by clonogenic assay. Results: 5-aza-dC treatment resulted in partial promoter demethylation and increased expression of hypermethylated candidate genes. A significant decrease of vital cell count, proliferation inhibition and increase of mortality was observed in 5-aza-dC-treated as well as in irradiated MB cells, whereby combination of both treatments led to additive effects. Although high-dose 5-aza-dC treatment was more effective in terms of demethylation, clonogenic assay revealed no differences between high- and low-dose settings indicating no relevance of 5-aza-dC-induced demethylation for decreased cell survival. MB cells pretreated with 5-aza-dC showed significantly lower plating efficiencies than untreated cells at all irradiation doses investigated. Analysis of surviving curves in irradiated MB cells, however, revealed no significant differences of {alpha}-, {beta}-values and 2-Gy surviving fraction with or without 5-aza-dC treatment. Conclusion: 5-aza-dC did not enhance radiation sensitivity of MB cells but significantly reduced the clonogenicity versus irradiation alone, which

Prolonged heart xenograft survival using combined total lymphoid irradiation and cyclosporine

International Nuclear Information System (INIS)

Knechtle, S.J.; Halperin, E.C.; Saad, T.; Bollinger, R.R.

1986-01-01

Total lymphoid irradiation and cyclosporine have profound immunosuppressive properties and permit successful heart allotransplantation. Cyclosporine used alone has not permitted consistently successful transplantation between species in all cases. Total lymphoid irradiation has not been applied to xenotransplantation. The efficacy of total lymphoid irradiation alone and in combination with cyclosporine was examined using an animal model of heart xenotransplantation. Heterotopic heart transplants were performed using inbred Syrian hamsters as donors and Lewis rats as recipients. Total lymphoid irradiation was administered preoperatively over 3 weeks for a total dose of 15 gray. Cyclosporine was started on the day of surgery and was given as a daily intramuscular injection of 2.5, 5, or 10 mg/kg/day until rejection was complete. Neither total lymphoid irradiation nor cyclosporine alone markedly prolonged graft survival. However, combined total lymphoid irradiation and cyclosporine, 5 or 10 mg/kg/day, dramatically prolonged graft survival to greater than 100 days in most recipients. There were no treatment-related deaths. In conclusion, combined total lymphoid irradiation and cyclosporine permit successful long-term survival of heart xenotransplants in this hamster-to-rat model

Induced variation in potato dry rot fusarium roseum by ultraviolet irradiation

International Nuclear Information System (INIS)

Lee, C.U.

1979-01-01

Variations were readily induced in Fusarium roseum isolated from decayed potato tubers by subjecting its conidia to ultraviolet irradiation. The dosage that resulted in complete absence of developing colonies in five minutes of irradiation did not cause the mortality of conidia for the initial one minute. Eighty eight precent of conidia were killed in three minutes. Approximately 90% of the conidia showed resistance to lethality for the initial two minutes whereas 10% began to show resistance after three minutes of the irradiation. The maximum 42% of color variation was obtained among the surviving conidia. Varients in both decreased and increased pathogenicity were induced in 8% among the color variants. Variations occurred in such other characteristics as growth rate, rigidity of mycelium, and conidia formation. (author)

Late radiation effects in animals surviving lethal irradiation

International Nuclear Information System (INIS)

Dimitrov, L.A.

1974-01-01

Animals (rats, mice, dogs) survived lethal irradiation by means of prophylactic-therapeutic treatments or previously irradiated, were studied for late radiation effects: life span, cachexia and fat growing of hypophysical type, tissue or organ hypoplasia manifested by disturbed hemopoiesis, suppressed function of adrenal gland, etc., suppressed immune reactivity of the irradiated organism, atypical biochemical changes in DNA and protein metabolism, epilation, chronic dermatitis, ulcerations, reduced reproductivity or full sterility, damage of kidneys leading to nephrosclerosis, dishormonal states, cataracts, diffuse sclerotic processes, various kinds of malignant and non-malignant tumors. In these cases hemopoiesis compensated for a definite time peripheral blood composition, but during the late period it showed features of incompleteness: shorter life survival of erythrocytes and thrombocytes manifested by a decreased binding of labelled methionine in these blood elements, anemia and relative thrombocytopenia sometimes with an increased number of polychromatic erythrocytes in peripheral blood and a decreased number of reticulocytes at the same time; lymphopenia and relative leucopenia with an increased number of hypersegmented neutrophils. Decreased reproductivity and atypical biochemical changes available in the first generation of the irradiated animals showed the probable role of mutagenic factors in the emergence of some late radiation effects. A significant part of late radiation sequences were due to neuro-endocrine desintegrations which lead to a disturbed supply of the vessels and afterwards to their sclerosis. Some of the described late radiation effects were also observed in biological controls as festures of ageing while in irradiated animals they were manifested in an earlier period. After application of optimal amounts radioprotectors (AET, cysteamine, serotonin) a more marked protective effect is demonstrated in the early reactions (time survival

Association of ultraviolet-induced retrovirus expression with anchorage-independent survival in rat embryo cells

International Nuclear Information System (INIS)

Suk, W.A.

1985-01-01

The authors have shown in the AI assay that the nontransforming retrovirus increases the differential in enhanced survival response in infected cultures. To more fully understand this aspect of the system, they examined the effect of UV irradiation on infected and uninfected FRE cells. In this communication the authors report that UV irradiation induces AI survival in infected and uninfected cells;in uninfected cells there is a concomitant induction of endogenous retrovirus expression. The AI survival of both cell lines was determined using a previously described procedure. Anchorage-dependent media control and solvent control cells, when suspended in medium above an agar base layer, showed a rapid decline in cell survival;however, cells that had been treated with carcinogen did not undergo the destructive process that took place in control cells, indicating specificity

Decreased Serum Hepatocyte Growth Factor (HGF in Individuals with Bipolar Disorder Normalizes after Zinc and Anti-oxidant Therapy

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A.J. Russo

2010-01-01

Full Text Available Aim To assess serum HGF concentration in individuals with bipolar disorder and investigate the efficacy of zinc therapy on these levels. Subjects and Methods Serum from 35 individuals diagnosed with bipolar disorder and 19 age and gender similar controls were tested for HGF concentration using ELISAs, and copper and zinc plasma levels using inductively-coupled plasma-mass spectrometry. Results HGF serum levels of individuals with bipolar disorder were significantly lower than age and gender similar controls ( P = 0.0021. HGF serum concentration was significantly lower in Bipolar patients pre-therapy ( P = 0.0009 and HGF levels normalized post-therapy. Zinc levels in these same individuals also normalized ( P = 0.0046 and patient's perceived severity of Bipolar symptoms significantly decreased after therapy ( P = 0.0003. We also found a significant direct correlation between Zinc and HGF serum concentration in the bipolar patients ( P = 0.04. Discussion These results suggest an association between low HGF levels and bipolar disorder and also demonstrate that zinc therapy may be associated with the normalization of HGF levels and decrease in severity of disease.

Hepatic regeneration after sublethal partial liver irradiation in cirrhotic rats

International Nuclear Information System (INIS)

Gu Ke; Lai Songtao; Ma Ningyi; Zhao Jiandong; Ren Zhigang; Wang Jian; Liu Jin; Jiang Guoliang

2011-01-01

Our previous animal study had demonstrated that partial liver irradiation (IR) could stimulate regeneration in the protected liver, which supported the measurements adopted in radiotherapy planning for hepatocellular carcinoma. The purpose of this present study is to investigate whether cirrhotic liver repopulation could be triggered by partial liver IR. The cirrhosis was induced by thioacetamide (TAA) in rats. After cirrhosis establishment, TAA was withdrawn. In Experiment 1, only right-half liver was irradiated with single doses of 5 Gy, 10 Gy and 15 Gy, respectively. In Experiment 2, right-half liver was irradiated to 15 Gy, and the left-half to 2.5 Gy, 5 Gy and 7.5 Gy, respectively. The regeneration endpoints, including liver index (LI); mitotic index (MI); liver proliferation index (LPI); proliferating cell nuclear antigen-labeling index (PCNA-LI); serum hepatic growth factor (HGF), vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-α and interleukin (IL)-6, were evaluated on 0 day, 30-day, 60-day, 90-day, 120-day and 150-day after IR. Serum and in situ TGF-β1 were also measured. In both experimental groups, the IR injuries were sublethal, inducing no more than 9% animal deaths. Upon TAA withdrawal, hepatic regeneration decelerated in the controls. In Experiment 1 except for LI, all other regeneration parameters were significantly higher than those in controls for both right-half and left-half livers. In Experiment 2 all regeneration parameters were also higher compared with those in controls for both half livers. Serum HGF and VEGF were increased compared with that of controls. Both unirradiated and low dose-irradiated cirrhotic liver were able to regenerate triggered by sublethal partial liver IR and higher doses and IR to both halves liver triggered a more enhanced regeneration. (author)

Late radiation effects in animals surviving lethal irradiation

Energy Technology Data Exchange (ETDEWEB)

Dimitrov, L A

1974-01-01

Animals (rats, mice, dogs) survived lethal irradiation by means of prophylactic-therapeutic treatments or previously irradiated, were studied for late radiation effects: life span, cachexia and fat growing of hypophysical type, tissue or organ hypoplasia manifested by disturbed hemopoiesis, suppressed function of adrenal gland, etc., suppressed immune reactivity of the irradiated organism, atypical biochemical changes in DNA and protein metabolism, epilation, chronic dermatitis, ulcerations, reduced reproductivity or full sterility, damage of kidneys leading to nephrosclerosis, dishormonal states, cataracts, diffuse sclerotic processes, various kinds of malignant and non-malignant tumors. In these cases hemopoiesis compensated for a definite time peripheral blood composition, but during the late period it showed features of incompleteness: shorter life survival of erythrocytes and thrombocytes manifested by a decreased binding of labelled methionine in these blood elements, anemia and relative thrombocytopenia sometimes with an increased number of polychromatic erythrocytes in peripheral blood and a decreased number of reticulocytes at the same time; lymphopenia and relative leucopenia with an increased number of hypersegmented neutrophils. Decreased reproductivity and atypical biochemical changes available in the first generation of the irradiated animals showed the probable role of mutagenic factors in the emergency of some late radiation effects. A significant part of late radiation sequences were due to neuro-endocrine disintegrations. Some of the described late radiation effects were also observed in biological controls as features of ageing. After application of radioprotectors (AET, cysteamine, serotonin) a more marked protective effect is demonstrated in the early reactions (time survival till 30th day, DNA and protein metabolism, immune reactions) of the lethally irradiated animals.

Gamma irradiation of isolated rat islets pretransplantation produces indefinite allograft survival in cyclosporine-treated recipients

International Nuclear Information System (INIS)

James, R.F.; Lake, S.P.; Chamberlain, J.; Thirdborough, S.; Bassett, P.D.; Mistry, N.; Bell, P.R.

1989-01-01

In this study we have examined the use of low-dose gamma-irradiation for the reduction of islet immunogenicity in the strong allogeneic combination of WAG rat islets transplanted into diabetic AUG recipients. First, we determined that gamma-irradiation reduced immunogenicity in vitro by use of a modified MLR with WAG islets as stimulators and AUG splenocytes as responders. We then determined the maximum dose of gamma-irradiation that could be used (250 rads) before islet function was affected. As 250 rads islet pretreatment alone was ineffective in prolonging allograft survival, we combined the pretreatment with a short course (days 0, 1, 2; 30 mg/kg) of cyclosporine. We found that CsA was only effective in significantly prolonging allograft survival when given subcutaneously in olive oil. The CsA treatment alone gave a significantly prolonged survival time for the islet allografts (median, 37 days vs. 6 days for controls), but when combined with the 250 rads islet pretreatment a synergistic effect was seen with 100% becoming long-term survivors (greater than 100 days). The long-term surviving AUG rats from both the CsA alone group and the CsA plus 250 rads pretreated islets group were challenged with WAG dendritic cells (DC). The islets from the 250 rads pretreated group were subsequently rejected (day 6) while the CsA alone group were not affected. The role of low dose gamma-irradiation when combined with CsA treatment of islet graft recipients in inducing specific unresponsiveness will be discussed

Gamma irradiation of isolated rat islets pretransplantation produces indefinite allograft survival in cyclosporine-treated recipients

Energy Technology Data Exchange (ETDEWEB)

James, R.F.; Lake, S.P.; Chamberlain, J.; Thirdborough, S.; Bassett, P.D.; Mistry, N.; Bell, P.R.

1989-06-01

In this study we have examined the use of low-dose gamma-irradiation for the reduction of islet immunogenicity in the strong allogeneic combination of WAG rat islets transplanted into diabetic AUG recipients. First, we determined that gamma-irradiation reduced immunogenicity in vitro by use of a modified MLR with WAG islets as stimulators and AUG splenocytes as responders. We then determined the maximum dose of gamma-irradiation that could be used (250 rads) before islet function was affected. As 250 rads islet pretreatment alone was ineffective in prolonging allograft survival, we combined the pretreatment with a short course (days 0, 1, 2; 30 mg/kg) of cyclosporine. We found that CsA was only effective in significantly prolonging allograft survival when given subcutaneously in olive oil. The CsA treatment alone gave a significantly prolonged survival time for the islet allografts (median, 37 days vs. 6 days for controls), but when combined with the 250 rads islet pretreatment a synergistic effect was seen with 100% becoming long-term survivors (greater than 100 days). The long-term surviving AUG rats from both the CsA alone group and the CsA plus 250 rads pretreated islets group were challenged with WAG dendritic cells (DC). The islets from the 250 rads pretreated group were subsequently rejected (day 6) while the CsA alone group were not affected. The role of low dose gamma-irradiation when combined with CsA treatment of islet graft recipients in inducing specific unresponsiveness will be discussed.

Effect of immunomodifier on radiation-induced antitumor immunity following local irradiation to tumor, 2

International Nuclear Information System (INIS)

Mukae, Shiro; Norimura, Toshiyuki; Tsuchiya, Takehiko

1988-01-01

This study was carried out to clarify whether or not the antitumor cell-mediated immunity of host is more effectively induced by the combined use of mouse interferon-α/β (MuIFN-α/β) with local irradiation than by simple local irradiation to tumor. C3H/He female mice, MM46 tumor cells and mouse interferon-α/β (MuIFN-α/β) were used in the experiment. Antitumor activity in mice was evaluated by the inhibition of tumor growth and mean survival days after treatment. Spleen cell killing activity to MM46 tumor cells was measured to evaluate the antitumor activity in vitro. In the case of single use of MuIFN-α/β, tumor growth was more rapid than in the non-treated group (control) in vivo. The mean survival days were also reduced. There was no siginificant difference in tumor growth inhibition between combined therapy using X-irradiation and MuIFN-α/β, and single therapy by local irradiation. However, in the case of administration of MuIFN-α/β after irradiation, the mean survival days was significantly increased compared with the group receiving X-ray irradiation only. (author)

IL-6 modulates hepatocyte proliferation via induction of HGF/p21cip1: Regulation by SOCS3

International Nuclear Information System (INIS)

Sun Rui; Jaruga, Barbara; Kulkarni, Shailin; Sun Haoyu; Gao Bin

2005-01-01

The precise role of IL-6 in liver regeneration and hepatocyte proliferation is controversial and the role of SOCS3 in liver regeneration remains unknown. Here we show that in vitro treatment with IL-6 inhibited primary mouse hepatocyte proliferation. IL-6 induced p21 cip1 protein expression in primary mouse hepatocytes. Disruption of the p21 cip1 gene abolished the inhibitory effect of IL-6 on cell proliferation. Co-culture with nonparenchymal liver cells diminished IL-6 inhibition of hepatocyte proliferation, which was likely due to IL-6 stimulation of nonparenchymal cells to produce HGF. Finally, IL-6 induced higher levels of p21 cip1 protein expression and a slightly stronger inhibition of cell proliferation in SOCS3 +/- mouse hepatocytes compared to wild-type hepatocytes, while liver regeneration was enhanced and prolonged in SOCS3 +/- mice. Our findings suggest that IL-6 directly inhibits hepatocyte proliferation via a p21 cip1 -dependent mechanism and indirectly enhances hepatocyte proliferation via stimulating nonparenchymal cells to produce HGF. SOCS3 negatively regulates liver regeneration

Hepatocyte growth factor, a determinant of airspace homeostasis in the murine lung.

Directory of Open Access Journals (Sweden)

Carla Calvi

Full Text Available The alveolar compartment, the fundamental gas exchange unit in the lung, is critical for tissue oxygenation and viability. We explored hepatocyte growth factor (HGF, a pleiotrophic cytokine that promotes epithelial proliferation, morphogenesis, migration, and resistance to apoptosis, as a candidate mediator of alveolar formation and regeneration. Mice deficient in the expression of the HGF receptor Met in lung epithelial cells demonstrated impaired airspace formation marked by a reduction in alveolar epithelial cell abundance and survival, truncation of the pulmonary vascular bed, and enhanced oxidative stress. Administration of recombinant HGF to tight-skin mice, an established genetic emphysema model, attenuated airspace enlargement and reduced oxidative stress. Repair in the TSK/+ mouse was punctuated by enhanced akt and stat3 activation. HGF treatment of an alveolar epithelial cell line not only induced proliferation and scattering of the cells but also conferred protection against staurosporine-induced apoptosis, properties critical for alveolar septation. HGF promoted cell survival was attenuated by akt inhibition. Primary alveolar epithelial cells treated with HGF showed improved survival and enhanced antioxidant production. In conclusion, using both loss-of-function and gain-of-function maneuvers, we show that HGF signaling is necessary for alveolar homeostasis in the developing lung and that augmentation of HGF signaling can improve airspace morphology in murine emphysema. Our studies converge on prosurvival signaling and antioxidant protection as critical pathways in HGF-mediated airspace maintenance or repair. These findings support the exploration of HGF signaling enhancement for diseases of the airspace.

Oral fibroblasts produce more HGF and KGF than skin fibroblasts in response to co-culture with keratinocytes

DEFF Research Database (Denmark)

Grøn, Birgitte; Stoltze, Kaj; Andersson, Anders

2002-01-01

The production of hepatocyte growth factor (HGF) and keratinocyte growth factor (KGF) in subepithelial fibroblasts from buccal mucosa, periodontal ligament, and skin was determined after co-culture with keratinocytes. The purpose was to detect differences between the fibroblast subpopulations...... days by ELISA. When cultured on polystyrene, the constitutive level of KGF and HGF in periodontal fibroblasts was higher than the level in buccal and skin fibroblasts. In the presence of keratinocytes, all three types of fibroblasts in general increased their HGF and KGF production 2-3 times. When...... cells were maintained in collagen, the level of HGF and KGF was decreased mainly in skin cultures. However, in oral fibroblasts, induction after stimulation was at a similar level in collagen compared to on polystyrene. Skin fibroblasts maintained in collagen produced almost no HGF whether...

Effect of irradiation on the survival of Salmonella in cooled meat

International Nuclear Information System (INIS)

Szczawinska, M.; Szczawinski, J.; Szulc, M.

1982-01-01

The effect of irradiation by X rays of 1, 2 and 3 kGy on the survival of Salmonella cells in meat during its storage at 0-2 0 C was investigated. The radioresistance of the Salmonella strains as well as the effect of irradiation on the organoleptic properties and shelf-life extension of meat was evaluated. Progressive dying of Salmonella cells which survived the irradiation was recorded during the storage of irradiated meat at 0-2 0 C. After irradiation and storage of meat at 8-10 0 C the number of bacteria decreased within the first days. Then, some of the strains were able to multiply, however after 14 days of storage, especially after irradiation with 3 kGy, the number of Salmonella was always lower than that immediately after irradiation. After the exposure to 3 kGy the shelf-life extension increased at least twice with the organoleptic properties changed insignificantly. (author)

Radiation-induced epigenetic alterations after low and high LET irradiations

International Nuclear Information System (INIS)

Aypar, Umut; Morgan, William F.; Baulch, Janet E.

2011-01-01

Epigenetics, including DNA methylation and microRNA (miRNA) expression, could be the missing link in understanding radiation-induced genomic instability (RIGI). This study tests the hypothesis that irradiation induces epigenetic aberrations, which could eventually lead to RIGI, and that the epigenetic aberrations induced by low linear energy transfer (LET) irradiation are different than those induced by high LET irradiations. GM10115 cells were irradiated with low LET X-rays and high LET iron (Fe) ions and evaluated for DNA damage, cell survival and chromosomal instability. The cells were also evaluated for specific locus methylation of nuclear factor-kappa B (NFκB), tumor suppressor in lung cancer 1 (TSLC1) and cadherin 1 (CDH1) gene promoter regions, long interspersed nuclear element 1 (LINE-1) and Alu repeat element methylation, CpG and non-CpG global methylation and miRNA expression levels. Irradiated cells showed increased micronucleus induction and cell killing immediately following exposure, but were chromosomally stable at delayed times post-irradiation. At this same delayed time, alterations in repeat element and global DNA methylation and miRNA expression were observed. Analyses of DNA methylation predominantly showed hypomethylation, however hypermethylation was also observed. We demonstrate that miRNA expression levels can be altered after X-ray irradiation and that these miRNA are involved in chromatin remodeling and DNA methylation. A higher incidence of epigenetic changes was observed after exposure to X-rays than Fe ions even though Fe ions elicited more chromosomal damage and cell killing. This distinction is apparent at miRNA analyses at which only three miRNA involved in two major pathways were altered after high LET irradiations while six miRNA involved in five major pathways were altered after low LET irradiations. This study also shows that the irradiated cells acquire epigenetic changes suggesting that epigenetic aberrations may arise in the

Radiation-induced epigenetic alterations after low and high LET irradiations

Energy Technology Data Exchange (ETDEWEB)

Aypar, Umut, E-mail: uaypa001@umaryland.edu [Department of Radiation Oncology, Radiation Oncology Research Laboratory, University of Maryland School of Medicine, Baltimore, MD 21201 (United States); Morgan, William F. [Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352 (United States); Baulch, Janet E. [Department of Radiation Oncology, Radiation Oncology Research Laboratory, University of Maryland School of Medicine, Baltimore, MD 21201 (United States)

2011-02-10

Epigenetics, including DNA methylation and microRNA (miRNA) expression, could be the missing link in understanding radiation-induced genomic instability (RIGI). This study tests the hypothesis that irradiation induces epigenetic aberrations, which could eventually lead to RIGI, and that the epigenetic aberrations induced by low linear energy transfer (LET) irradiation are different than those induced by high LET irradiations. GM10115 cells were irradiated with low LET X-rays and high LET iron (Fe) ions and evaluated for DNA damage, cell survival and chromosomal instability. The cells were also evaluated for specific locus methylation of nuclear factor-kappa B (NF{kappa}B), tumor suppressor in lung cancer 1 (TSLC1) and cadherin 1 (CDH1) gene promoter regions, long interspersed nuclear element 1 (LINE-1) and Alu repeat element methylation, CpG and non-CpG global methylation and miRNA expression levels. Irradiated cells showed increased micronucleus induction and cell killing immediately following exposure, but were chromosomally stable at delayed times post-irradiation. At this same delayed time, alterations in repeat element and global DNA methylation and miRNA expression were observed. Analyses of DNA methylation predominantly showed hypomethylation, however hypermethylation was also observed. We demonstrate that miRNA expression levels can be altered after X-ray irradiation and that these miRNA are involved in chromatin remodeling and DNA methylation. A higher incidence of epigenetic changes was observed after exposure to X-rays than Fe ions even though Fe ions elicited more chromosomal damage and cell killing. This distinction is apparent at miRNA analyses at which only three miRNA involved in two major pathways were altered after high LET irradiations while six miRNA involved in five major pathways were altered after low LET irradiations. This study also shows that the irradiated cells acquire epigenetic changes suggesting that epigenetic aberrations may arise

DNA synthesis and cell survival after X-irradiation of mammalian cells treated with caffeine or adenine

International Nuclear Information System (INIS)

Griffiths, T.D.; Carpenter, J.G.; Dahle, D.B.

1978-01-01

The expression of the transient depression in the rate of DNA synthesis normally observed after exposure of randomly-dividing Chinese hamster V-79 or Chinese hamster CHO cells to ionizing radiation could be postponed by a post-irradiation treatment with 1.0 to 2.0 mM adenine or 1.5 mM caffeine. Caffeine may exert its effect by creating additional sites for replication in irradiated cells. Cells treated with caffeine or adenine for 2 or 4 hours after exposure to 3000 rad of 300 kVp X-rays exhibited depressed synthesis only after the removal of caffeine or adenine. These alterations in the timing of the X-ray-induced depression of the rate of DNA synthesis had no effect on X-ray-induced cell killing. Although a 4 hour post-irradiation treatment of randomly-dividing Chinese hamster V-79 cells with 1.0 or 2.0 mM caffeine potentiated X-ray-induced cell killing, this reduction in survival was due primarily to effects on cells not in S-phase. (author)

Decreased Hepatocyte Growth Factor (HGF) and Gamma Aminobutyric Acid (GABA) in Individuals with Obsessive-Compulsive Disorder (OCD).

Science.gov (United States)

Russo, Anthony J; Pietsch, Stefanie C

2013-01-01

There is support for the role of gamma aminobutyric acid (GABA) in the etiology of mood disorders. Recent research has shown that hepatocyte growth factor (HGF) modulates GABAergic inhibition and seizure susceptibility. This study was designed to determine and correlate plasma levels of HGF and GABA as well as symptom severity in individuals with obsessive-compulsive disorder (OCD). Plasma from 15 individuals with OCD (9 males, 6 females;, mean age 38.7 years) and 17 neurotypical controls (10 males, 7 females; mean age 35.2 years) was assessed for HGF, GABA, urokinase plasminogen activator (uPA), and urokinase plasminogen activator receptor (uPAR) concentration using enzyme-linked immunosorbest assays ELISAs. Symptom severity was assessed in these OCD individuals and compared with HGF and GABA concentrations. In this preliminary study, individuals with OCD had significantly decreased HGF levels, decreased plasma levels of GABA and decreased uPA. We found that both uPA and uPAR levels correlate with HGF. Both low uPA and low uPAR levels correlate with high symptom severity in individuals with OCD. Low GABA levels in OCD individuals also correlate with high symptom severity. These results demonstrate a preliminary association between HGF, GABA, uPA levels, and OCD and suggest that plasma GABA and uPA levels are related to symptom severity in individuals with OCD.

Expression of p53/HGF/c-met/STAT3 signal in fetuses with neural tube defects.

Science.gov (United States)

Trovato, Maria; D'Armiento, Maria; Lavra, Luca; Ulivieri, Alessandra; Dominici, Roberto; Vitarelli, Enrica; Grosso, Maddalena; Vecchione, Raffaella; Barresi, Gaetano; Sciacchitano, Salvatore

2007-02-01

Neural tube defects (NTD) are morphogenetic alterations due to a defective closure of neural tube. Hepatocyte growth factor (HGF)/c-met system plays a role in morphogenesis of nervous system, lung, and kidney. HGF/c-met morphogenetic effects are mediated by signal transducers and activators of transcription (STAT)3 and both HGF and c-met genes are regulated from p53. The aim of our study was to analyze mRNA and protein expressions of p53, HGF, c-met, and STAT3 in fetuses with NTD. By reverse transcriptase-polymerase chain reaction and immunohistochemistry, we analyzed neural tissues from four NTD fetuses and the corresponding non-malformed lungs, kidneys and placentas. We found a reduced mRNA expression of HGF/c-met/STAT3 pathway, in the malformed nervous systems and placentas. The reduced expression of this pathway correlated with the absence of p53 in all these samples. On the contrary, detectable expression levels of p53, HGF, c-met, and STAT3 were observed in non-malformed lungs and kidneys obtained from the same fetuses. Comparable results were obtained by immunohistochemistry, with the exception of p53, which was undetected in all fetal tissues. In conclusion, in NTD fetuses, both the defective neural tube tissue and the placenta have a reduction in all components of the p53/HGF/c-met/STAT3 cascade. This raises the possibility of using the suppression of these genes for early diagnosis of NTD especially on chorionic villus sampling.

Hepatocyte growth factor enhances death receptor-induced apoptosis by up-regulating DR5

International Nuclear Information System (INIS)

Li, Yang; Fan, Xing; Goodwin, C Rory; Laterra, John; Xia, Shuli

2008-01-01

Hepatocyte growth factor (HGF) and its receptor c-MET are commonly expressed in malignant gliomas and embryonic neuroectodermal tumors including medulloblastoma and appear to play an important role in the growth and dissemination of these malignancies. Dependent on cell context and the involvement of specific downstream effectors, both pro- and anti-apoptotic effects of HGF have been reported. Human medulloblastoma cells were treated with HGF for 24–72 hours followed by death receptor ligand TRAIL (Tumor necrosis factor-related apoptosis-inducing ligand) for 24 hours. Cell death was measured by MTT and Annexin-V/PI flow cytometric analysis. Changes in expression levels of targets of interest were measured by Northern blot analysis, quantitative reverse transcription-PCR, Western blot analysis as well as immunoprecipitation. In this study, we show that HGF promotes medulloblastoma cell death induced by TRAIL. TRAIL alone triggered apoptosis in DAOY cells and death was enhanced by pre-treating the cells with HGF for 24–72 h prior to the addition of TRAIL. HGF (100 ng/ml) enhanced TRAIL (10 ng/ml) induced cell death by 36% (P < 0.001). No cell death was associated with HGF alone. Treating cells with PHA-665752, a specific c-Met receptor tyrosine kinase inhibitor, significantly abrogated the enhancement of TRAIL-induced cell death by HGF, indicating that its death promoting effect requires activation of its canonical receptor tyrosine kinase. Cell death induced by TRAIL+HGF was predominately apoptotic involving both extrinsic and intrinsic pathways as evidenced by the increased activation of caspase-3, 8, 9. Promotion of apoptosis by HGF occurred via the increased expression of the death receptor DR5 and enhanced formation of death-inducing signal complexes (DISC). Taken together, these and previous findings indicate that HGF:c-Met pathway either promotes or inhibits medulloblastoma cell death via pathway and context specific mechanisms

MiRNA-486 regulates angiogenic activity and survival of mesenchymal stem cells under hypoxia through modulating Akt signal

Energy Technology Data Exchange (ETDEWEB)

Shi, Xue-Feng [High Altitude Medicine of Ministry of Chinese Education and Research Center for High Altitude Medicine, Qinghai University, Xining 810001 (China); Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850 (China); Department of Respiration, Qinghai Provincial People' s Hospital, Xining (China); Wang, Hua; Xiao, Feng-Jun [Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850 (China); Yin, Yue [Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850 (China); Department of Hematology, Peking University First Hospital, Beijing (China); Xu, Qin-Qin [High Altitude Medicine of Ministry of Chinese Education and Research Center for High Altitude Medicine, Qinghai University, Xining 810001 (China); Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850 (China); Ge, Ri-Li, E-mail: geriligao@hotmail.com [High Altitude Medicine of Ministry of Chinese Education and Research Center for High Altitude Medicine, Qinghai University, Xining 810001 (China); Wang, Li-Sheng, E-mail: wangls@bmi.ac.cn [Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850 (China)

2016-02-12

MicroRNA-486 (miR-486) was first identified from human fetal liver cDNA library and validated as a regulator of hematopoiesis. Its roles in regulating the biological function of bone marrow-derived mesnechymal stem cells (BM-MSCs) under hypoxia have not been explored yet. In this study, we demonstrated that exposure to hypoxia upregulates miR-486 expression in BM-MSCs. Lentivirus-mediated overexpression of miR-486 resulted in increase of hepatocyte growth factor (HGF) and vascular endothelial growth factor(VEGF) in both mRNA and protein levels. MiR-486 expression also promotes proliferation and reduces apoptosis of BM-MSCs. Whereas MiR-486 knockdown downregulated the secretion of HGF and VEGF and induced apoptosis of BM-MSCs. Furthermore, PTEN-PI3K/AKT signaling was validated to be involved in changes of BM-MSC biological functions regulated by miR-486. These results suggested that MiR-486 mediated the hypoxia-induced angiogenic activity and promoted the proliferation and survival of BM-MSCs through regulating PTEN-PI3K/AKT signaling. These findings might provide a novel understanding of effective therapeutic strategy for hypoxic-ischemic diseases. - Highlights: • miR-486 is a hypoxia-induced miRNA. • miR-486 regulates the secretion of HGF and VEGF, promotes proliferation, and inhibits apoptosis of BM-MSCs. • miR-486 enhances PI3K/AKT activity signaling by targeting PTEN molecule.

Radioprotective effect of cimitidine on acutely irradiated mice survival and hematopoietic system

Directory of Open Access Journals (Sweden)

Qing-rong WANG

2017-02-01

Full Text Available Objective　To investigate the radioprotective effect of cimetidine on survival rate and hematopoietic system in acutely irradiated mice. Methods　The total body irradiation doses were 6.0Gy and 8.0Gy respectively at 1.01Gy/min rate. Sixty healthy male C57BL/6 mice were randomly divided into control group, model group, positive-drug (523 group and cimetidine groups (33.3mg/kg, 100mg/kg and 300mg/kg. Each group had ten mice. The mice were given intragastric administration of cimetidine for 6d before the irradiation in cimetidine groups, and 523 was administered before irradiation once a day for one day in 523 group, and at 5h after irradiation, was given again. The 30d survival rate after 8.0Gy irradiation was recorded. The peripheral blood cells, bone marrow DNA content and frequency of micronucleated polychromatic erythrocytes (fMNPCE were determined 30d after 6.0Gy irradiation. Results　After 8.0Gy irradiation, all the mice died on 21th day in model control group. The survival rates in cimetidine groups were 50%, 20% and 30%, respectively. After 6.0Gy irradiation on 30th day, compared with control group, the peripheral white blood cells (WBC and bone marrow DNA content were decreased significantly (P<0.01, P<0.05 in model group, and fMNPCE was increased significantly (P<0.05. Compared with model group, WBC was significantly increased in 300mg/kg cimetidine group (P<0.01. In cimetidine groups, the bone marrow DNA content was increased significantly after irradiation (P<0.01 or P<0.05, and the fMNPCE was decreased significantly (P<0.01 or P<0.05and tended towards normal. Conclusion　Cimetidine could improve 30d survival rate of acutely irradiated mice and has good protective effect on hematopoietic system. DOI: 10.11855/j.issn.0577-7402.2017.01.12

The TAM-family receptor Mer mediates production of HGF through the RhoA-dependent pathway in response to apoptotic cells.

Science.gov (United States)

Park, Hyun-Jung; Baen, Ji-Yeon; Lee, Ye-Ji; Choi, Youn-Hee; Kang, Jihee Lee

2012-08-01

The TAM receptor protein tyrosine kinases Tyro3, Axl, and Mer play important roles in macrophage function. We investigated the roles of the TAM receptors in mediating the induction of hepatocyte growth factor (HGF) during the interaction of macrophages with apoptotic cells. Mer-specific neutralizing antibody, small interfering RNA (siRNA), and a recombinant Mer protein (Mer/Fc) inhibited HGF mRNA and protein expression, as well as activation of RhoA, Akt, and specific mitogen-activated protein (MAP) kinases in response to apoptotic cells. Inhibition of Axl or Tyro3 with specific antibodies, siRNA, or Fc-fusion proteins did not prevent apoptotic cell-induced HGF mRNA and protein expression and did not inhibit activation of the postreceptor signaling molecules RhoA and certain MAP kinases, including extracellular signal-regulated protein kinase and c-Jun NH(2)-terminal kinase. However, Axl- and Tyro3-specific blockers did inhibit the activation of Akt and p38 MAP kinase in response to apoptotic cells. In addition, none of the TAM receptors mediated the effects of apoptotic cells on transforming growth factor-β or epidermal growth factor mRNA expression. However, they were involved in the induction of vascular endothelial growth factor mRNA expression. Our data provide evidence that when macrophages interact with apoptotic cells, only Mer of the TAM-family receptors is responsible for mediating transcriptional HGF production through a RhoA-dependent pathway.

A case of irradiation-induced malignant fibrous histiocytoma after an operation for rectal cancer

International Nuclear Information System (INIS)

Tahara, Hiroyuki; Kuroda, Yoshinori; Kuranishi, Fumito; Toyota, Kazuhiro; Nakahara Masahiro

2004-01-01

We recently observed a case of presumed irradiation-induced malignant fibrous histiocytoma (MFH), which developed 11 years after postoperative chemoradiotherapy for residual rectal cancer. A 65-year-old female underwent chemoradiotherapy for the residual tumor on the sacrum after abdominoperineal resection for rectal cancer in 1991. She showed no evidence of local recurrence or distant metastasis. Biopsy and MRI in 2002 suggested a retroperitoneal malignant tumor associated with invasion of the uterus and the sacrum, and the patient subsequently underwent surgery. Histopathologically the tumor was MFH. This case was considered to be an irradiation-induced secondary malignant tumor, according to the criteria developed by Arlen et al. In elderly patients and cases that underwent chemoradiotherapy, the latency period of irradiation-induced secondary malignant tumor tends to be shorter. If the progress of postoperative adjuvant chemotherapy increases the number of long-term surviving cases in the future, the incidence of irradiation-induced secondary malignant tumor will increase. It is therefore necessary to survey these cases over a longer period of time after surgery. (author)

Radiation-Induced Epigenetic Alterations after Low and High LET Irradiations

Energy Technology Data Exchange (ETDEWEB)

Aypar, Umut; Morgan, William F.; Baulch, Janet E.

2011-02-01

Epigenetics, including DNA methylation and microRNA (miRNA) expression, could be the missing link in understanding the delayed, non-targeted effects of radiation including radiationinduced genomic instability (RIGI). This study tests the hypothesis that irradiation induces epigenetic aberrations, which could eventually lead to RIGI, and that the epigenetic aberrations induced by low linear energy transfer (LET) irradiation are different than those induced by high LET irradiations. GM10115 cells were irradiated with low LET x-rays and high LET iron (Fe) ions and evaluated for DNA damage, cell survival and chromosomal instability. The cells were also evaluated for specific locus methylation of nuclear factor-kappa B (NFκB), tumor suppressor in lung cancer 1 (TSLC1) and cadherin 1 (CDH1) gene promoter regions, long interspersed nuclear element 1 (LINE-1) and Alu repeat element methylation, CpG and non-CpG global methylation and miRNA expression levels. Irradiated cells showed increased micronucleus induction and cell killing immediately following exposure, but were chromosomally stable at delayed times post-irradiation. At this same delayed time, alterations in repeat element and global DNA methylation and miRNA expression were observed. Analyses of DNA methylation predominantly showed hypomethylation, however hypermethylation was also observed. MiRNA shown to be altered in expression level after x-ray irradiation are involved in chromatin remodeling and DNA methylation. Different and higher incidence of epigenetic changes were observed after exposure to low LET x-rays than high LET Fe ions even though Fe ions elicited more chromosomal damage and cell killing. This study also shows that the irradiated cells acquire epigenetic changes even though they are chromosomally stable suggesting that epigenetic aberrations may arise in the cell without initiating RIGI.

Solar irradiance limits the long-term survival of Listeria monocytogenes in seawater.

Science.gov (United States)

NicAogáin, K; Magill, D; O'Donoghue, B; Conneely, A; Bennett, C; O'Byrne, C P

2018-03-01

Seafood has often been implicated in outbreaks of food-borne illness caused by Listeria monocytogenes but the source of contamination is usually not known. In this study we investigated the possibility that this pathogen could survive in seawater for an extended time period. Freshly collected seawater samples were inoculated with 1 × 10 8  CFU per ml of L. monocytogenes EGD-e and survival was monitored by plate counting for up to 25 days. When incubated in the dark, either at ambient temperatures (4-14°C) or at 16°C, >10 4  CFU per ml survivors were present after 25 days. However, when the seawater cell suspensions were exposed to ambient light (solar irradiation) and temperatures, L. monocytogenes lost viability rapidly and no survivors could be detected after the 80 h time point. Both UV-A and visible light in the blue region of the spectrum (470 nm) were found to contribute to this effect. The stress inducible sigma factor σ B was found to play a role in survival of L. monocytogenes in seawater. Together these data demonstrate that solar irradiation is a critical determinant of L. monocytogenes survival in marine environments. The data further suggest the possibility of controlling this food-borne pathogen in food-processing environments using visible light. Listeria monocytogenes is a food-borne bacterial pathogen capable of causing the life-threatening infection, listeriosis. In seafood the route of contamination from the environment is often not well understood as this pathogen is not generally thought to survive well in seawater. Here we provide evidence that L. monocytogenes is capable of surviving for long periods of time in seawater when light is excluded. Sunlight is demonstrated to have a significant effect on the survival of this pathogen in seawater, and both visible (470 nm) and UV-A light are shown to contribute to this effect. © 2017 The Society for Applied Microbiology.

Irradiation strongly reduces tumorigenesis of human induced pluripotent stem cells

International Nuclear Information System (INIS)

Inui, Shoki; Minami, Kazumasa; Ito, Emiko; Imaizumi, Hiromasa; Mori, Seiji; Koizumi, Masahiko; Fukushima, Satsuki; Miyagawa, Shigeru; Sawa, Yoshiki; Matsuura, Nariaki

2017-01-01

Induced pluripotent stem (iPS) cells have demonstrated they can undergo self-renewal, attain pluripotency, and differentiate into various types of functional cells. In clinical transplantation of iPS cells, however, a major problem is the prevention of tumorigenesis. We speculated that tumor formation could be inhibited by means of irradiation. Since the main purpose of this study was to explore the prevention of tumor formation in human iPS (hiPS) cells, we tested the effects of irradiation on tumor-associated factors such as radiosensitivity, pluripotency and cell death in hiPS cells. The irradiated hiPS cells showed much higher radiosensitivity, because the survival fraction of hiPS cells irradiated with 2 Gy was < 10%, and there was no change of pluripotency. Irradiation with 2 and 4 Gy caused substantial cell death, which was mostly the result of apoptosis. Irradiation with 2 Gy was detrimental enough to cause loss of proliferation capability and trigger substantial cell death in vitro. The hiPS cells irradiated with 2 Gy were injected into NOG mice (NOD/Shi-scid, IL-2 Rγnull) for the analysis of tumor formation. The group of mice into which hiPS cells irradiated with 2 Gy was transplanted showed significant suppression of tumor formation in comparison with that of the group into which non-irradiated hiPS cells were transplanted. It can be presumed that this diminished rate of tumor formation was due to loss of proliferation and cell death caused by irradiation. Our findings suggest that tumor formation following cell therapy or organ transplantation induced by hiPS cells may be prevented by irradiation.

Novel biomarker-based model for the prediction of sorafenib response and overall survival in advanced hepatocellular carcinoma: a prospective cohort study.

Science.gov (United States)

Kim, Hwi Young; Lee, Dong Hyeon; Lee, Jeong-Hoon; Cho, Young Youn; Cho, Eun Ju; Yu, Su Jong; Kim, Yoon Jun; Yoon, Jung-Hwan

2018-03-20

Prediction of the outcome of sorafenib therapy using biomarkers is an unmet clinical need in patients with advanced hepatocellular carcinoma (HCC). The aim was to develop and validate a biomarker-based model for predicting sorafenib response and overall survival (OS). This prospective cohort study included 124 consecutive HCC patients (44 with disease control, 80 with progression) with Child-Pugh class A liver function, who received sorafenib. Potential serum biomarkers (namely, hepatocyte growth factor [HGF], fibroblast growth factor [FGF], vascular endothelial growth factor receptor-1, CD117, and angiopoietin-2) were tested. After identifying independent predictors of tumor response, a risk scoring system for predicting OS was developed and 3-fold internal validation was conducted. A risk scoring system was developed with six covariates: etiology, platelet count, Barcelona Clinic Liver Cancer stage, protein induced by vitamin K absence-II, HGF, and FGF. When patients were stratified into low-risk (score ≤ 5), intermediate-risk (score 6), and high-risk (score ≥ 7) groups, the model provided good discriminant functions on tumor response (concordance [c]-index, 0.884) and 12-month survival (area under the curve [AUC], 0.825). The median OS was 19.0, 11.2, and 6.1 months in the low-, intermediate-, and high-risk group, respectively (P functions on tumor response (c-index, 0.825) and 12-month survival (AUC, 0.803), and good calibration functions (all P > 0.05 between expected and observed values). This new model including serum FGF and HGF showed good performance in predicting the response to sorafenib and survival in patients with advanced HCC.

Prolongation of experimental islet transplant survival by fractionated splenic irradiation

International Nuclear Information System (INIS)

Kolb, E.; Casanova, M.; Largiader, F.

1980-01-01

Experiments designed to delay the rejection of intrasplenic pancreatic fragment allotransplants in dogs showed increased transplant survival times from 3.1 days (controls) to 5.5 days with fractionated splenic irradiation and to 7.5 days with combined local irradiation and immunosuppressive chemotherapy. Drug treatment alone had no beneficial effect

X-irradiation-induced emesis in Suncus murinus

International Nuclear Information System (INIS)

Torii, Yoshifumi; Saito, Hiroshi; Matsuki, Norio; Shikita, Mikio.

1993-01-01

X-irradiation-induced emesis was investigated in Suncus murinus, a house musk shrew. Whole body X-irradiation caused emesis, and the calculated ED 50 value that induced emesis in 50% of animals was 429 cGy. At the irradiation dose of 800 cGy all the animals vomited 10.0±2.4 times with a latency of 20.0±2.9 min. The emetogenic effect of X-irradiation was dependent on the part of the body exposed. Abdominal X-irradiation at 1000 cGy caused emesis in all animals studied, whereas the same dose to the head had no emetogenic effect. We investigated several prophylactic methods against X-irradiation-induced emesis. Surgical vagotomy completely inhibited the emesis induced by 800 cGy X-irradiation. Emesis was also prevented by the subcutaneous administration of tropisetron (ICS 205-930, a selective serotonergic 5-HT 3 receptor antagonist) with an ID 50 value of 29 μg/kg. These results suggest that (1) suncus is a useful experimental animal for the study of radiation-induced emesis and the development of prophylactic drugs, (2) serotonin plays an important role in X-irradiation-induced emesis, and (3) X-irradiation-induced emesis is very similar to that caused by cancer chemotherapeutic agents. (author)

Evidence that survival of γ-irradiated Escherichia coli is influenced by membrane fluidity

International Nuclear Information System (INIS)

Yatvin, M.B.

1976-01-01

Survival studies have been carried out on an Escherichia coli auxotroph (K-12 strain K1060) defective in both fatty acid degradation and in unsaturated fatty acid biosynthesis. Cultures were grown overnight in media supplemented with either oleic or linolenic acid, and γ-irradiated at two temperatures. Gas chromatography of total cellular fatty acids demonstrated marked differences in the compositions. In the bacteria grown in oleate, plamitate accounted for 35% and oleate 43%, whereas those grown in linolenate had no oleate but contained 56% palmitate and 35% linolenate. The loss (35%) in total DNA radioactivity from ( 3 H)TdR labelled cells after irradiation at room temperature or on ice, was essentially the same in bacteria grown with linoleic or oleic acid medium. The survival of linolenic substituted bacteria was altered little by irradiation at ice-bath temperature, but the oleic-grown bacteria were much more radiosensitive when irradiated and plated from the cold. The temperatures of the membrane phase transitions are such that at ice-bath temperature (approximately 3 to 5 0 C) only the membrane of the linolenate grown bacteria could possibly still be in the liquid (unorganized) state. The results therefore indicate that one of the factors influencing survival of irradiated bacteria may be membrane fluidity, and the membranes are an important factor in determining the extent of damage, 'repair' and ultimate survival in irradiated cells. (U.K.)

Tanacetum parthenium leaf extract mediated survival protection in lethally irradiated Swiss albino mice

International Nuclear Information System (INIS)

Shetty, Prashanth; Pooja, S.; Suchetha Kumari, N.; Shetty, Jayaram; Peter, Alex John; Jose, Jerish M.

2016-01-01

Search for less-toxic radioprotectors has spurred interest in the development of natural products. In Ayurveda, the traditional medicine, Tanacetum species have been used to treat ailments since ancient times throughout the world. Effects of the administration of different concentrations of Tanacetum parthenium leaf aqueous extract (TPLA), Tanacetum parthenium leaf ethanolic extract (TPLE) were investigated in Swiss albino mice. Mice (20-25 g) were randomly divided into 8 groups of ten animals each. The control group and the radiation group were treated daily with oral administration of saline for 15 days. Each subgroups of TPLA and TPLE were treated with doses of 50, 100 and 250 mg/kg daily for 15 days. On the 15th day, all were irradiated with 10 Gy whole body irradiation. Survival was observed daily up to 30th post-irradiation day. Data were analysed using the Kaplan-Meier survival curves. The significance difference in survival between control, radiation and treatment groups were observed (P < 0.001). Current studies revealed the protective effect of Tanacetum parthenium rendering high survivability in lethally irradiated mice. (author)

Leptin deficiency-induced obesity exacerbates ultraviolet B radiation-induced cyclooxygenase-2 expression and cell survival signals in ultraviolet B-irradiated mouse skin

International Nuclear Information System (INIS)

Sharma, Som D.; Katiyar, Santosh K.

2010-01-01

Obesity has been implicated in several inflammatory diseases and in different types of cancer. Chronic inflammation induced by exposure to ultraviolet (UV) radiation has been implicated in various skin diseases, including melanoma and nonmelanoma skin cancers. As the relationship between obesity and susceptibility to UV radiation-caused inflammation is not clearly understood, we assessed the role of obesity on UVB-induced inflammation, and mediators of this inflammatory response, using the genetically obese (leptin-deficient) mouse model. Leptin-deficient obese (ob/ob) mice and wild-type counterparts (C57/BL6 mice) were exposed to UVB radiation (120 mJ/cm 2 ) on alternate days for 1 month. The mice were then euthanized and skin samples collected for analysis of biomarkers of inflammatory responses using immunohistochemistry, western blotting, ELISA and real-time PCR. Here, we report that the levels of inflammatory responses were higher in the UVB-exposed skin of the ob/ob obese mice than those in the UVB-exposed skin of the wild-type non-obese mice. The levels of UVB-induced cyclooxygenase-2 expression, prostaglandin-E 2 production, proinflammatory cytokines (i.e., tumor necrosis factor-α, interleukin-1β, interleukin-6), and proliferating cell nuclear antigen and cell survival signals (phosphatidylinositol-3-kinase and p-Akt-Ser 473 ) were higher in the skin of the ob/ob obese mice than the those in skin of their wild-type non-obese counterparts. Compared with the wild-type non-obese mice, the leptin-deficient obese mice also exhibited greater activation of NF-κB/p65 and fewer apoptotic cells in the UVB-irradiated skin. Our study suggests for the first time that obesity in mice is associated with greater susceptibility to UVB-induced inflammatory responses and, therefore, obesity may increase susceptibility to UVB-induced inflammation-associated skin diseases, including the risk of skin cancer.

Possible radiation induced cancer of the thoracic esophagus after postoperative irradiation for the breast cancer

International Nuclear Information System (INIS)

Ueda, Mamoru; Matsubara, Toshiki; Kasumi, Fujio; Nishi, Mitsumasa; Kajitani, Tamaki

1991-01-01

We report 11 patients with cancer of the thoracic esophagus developing after postoperative irradiation therapy for breast cancer. Irradiation was done immediately after mastectomy in these patients and the irradiation field included the unilateral or bilateral parasternal region. They received a total dose ranging from 35 Gy to 60 Gy and the dose received to the thoracic esophagus was estimated from 10 Gy to 48 Gy. All cancer sites were involved in the irradiation field. The latent intervals of 10 patients from radiation to the manifest of cancer ranged from 10 to 19 years. Among 4777 women undergoing mastectomy for breast cancer between 1946 and 1980 in our hospital, 8 women (0.17%) developed cancer of the thoracic esophagus, whereas 5 (0.335%) out of 1534 women treated with mastectomy and radiotherapy with Linac between 1964 and 1980 developed cancer of the thoracic esophagus. Higher incidence of esophageal cancer in patients treated with surgery and radiation suggests that these cancers might be induced by radiation. Eight patients had esophagectomy and 4 patients of them received postoperative irradiation. They have survived from 9 months to 13 years. Two patients were controlled well by the irradiation alone. It is interesting that radiation therapy is sensitive to the possible radiation induced cancer of the thoracic esophagus. Follow up study should be directed to the possible development of second malignancy in patients who survive for a long time after radiation therapy. (author)

Electron-irradiation-induced phase transformation in alumina

International Nuclear Information System (INIS)

Chen, C.L.; Arakawa, K.; Lee, J.-G.; Mori, H.

2010-01-01

In this study, electron-irradiation-induced phase transformations between alumina polymorphs were investigated by high-resolution transmission electron microscopy. It was found that the electron-irradiation-induced α → κ' phase transformation occurred in the alumina under 100 keV electron irradiation. It is likely that the knock-on collision between incident electrons and Al 3+ cations is responsible for the occurrence of electron-irradiation-induced phase transformation from α-alumina to κ'-alumina.

A theoretical study on the influence of the homogeneity of heavy-ion irradiation field on the survival fraction of cells

International Nuclear Information System (INIS)

Wen Xiaoqiong; Li Qiang; Zhou Guangming; Li Wenjian; Wang Jufang; Wei Zengquan

2001-01-01

In order to provide theoretical basis for the homogeneity request of heavy-ion irradiation field, the most important design parameter of the heavy-ion radiotherapy facility planned in IMP (Institute of Modern Physics), the influence of the homogeneity of heavy-ion irradiation field on the survival fraction of cells was investigated theoretically. A formula for survival fraction of cells irradiated by the un-uniform heavy-ion irradiation field was deduced to estimate the influence of the homogeneity of heavy-ion irradiation field on the survival fraction of cells. The results show that the survival fraction of cells irradiation by the un-uniform irradiation field is larger than that of cells irradiated by the uniform irradiation field, and the survival fraction of cells increases as the homogeneity of heavy-ion irradiation field decreasing. Practically, the heavy-ion irradiation field can be treated as uniform irradiation field when its homogeneity is better than 95%. According to these results, design request for the homogeneity of heavy-ion irradiation field should be better than 95%. The present results also show that the agreement of homogeneity of heavy-ion irradiation field must be checked while comparing the survival fraction curves obtained by different laboratory

Response of thyroid follicular cells to gamma irradiation compared to proton irradiation. I. Initial characterization of DNA damage, micronucleus formation, apoptosis, cell survival, and cell cycle phase redistribution

Science.gov (United States)

Green, L. M.; Murray, D. K.; Bant, A. M.; Kazarians, G.; Moyers, M. F.; Nelson, G. A.; Tran, D. T.

2001-01-01

The RBE of protons has been assumed to be equivalent to that of photons. The objective of this study was to determine whether radiation-induced DNA and chromosome damage, apoptosis, cell killing and cell cycling in organized epithelial cells was influenced by radiation quality. Thyroid-stimulating hormone-dependent Fischer rat thyroid cells, established as follicles, were exposed to gamma rays or proton beams delivered acutely over a range of physical doses. Gamma-irradiated cells were able to repair DNA damage relatively rapidly so that by 1 h postirradiation they had approximately 20% fewer exposed 3' ends than their counterparts that had been irradiated with proton beams. The persistence of free ends of DNA in the samples irradiated with the proton beam implies that either more initial breaks or a quantitatively different type of damage had occurred. These results were further supported by an increased frequency of chromosomal damage as measured by the presence of micronuclei. Proton-beam irradiation induced micronuclei at a rate of 2.4% per gray, which at 12 Gy translated to 40% more micronuclei than in comparable gamma-irradiated cultures. The higher rate of micronucleus formation and the presence of larger micronuclei in proton-irradiated cells was further evidence that a qualitatively more severe class of damage had been induced than was induced by gamma rays. Differences in the type of damage produced were detected in the apoptosis assay, wherein a significant lag in the induction of apoptosis occurred after gamma irradiation that did not occur with protons. The more immediate expression of apoptotic cells in the cultures irradiated with the proton beam suggests that the damage inflicted was more severe. Alternatively, the cell cycle checkpoint mechanisms required for recovery from such damage might not have been invoked. Differences based on radiation quality were also evident in the alpha components of cell survival curves (0.05 Gy(-1) for gamma rays, 0

Cell Survival and DNA Damage in Normal Prostate Cells Irradiated Out-of-Field.

LENUS (Irish Health Repository)

Shields, L

2014-10-31

Interest in out-of-field radiation dose has been increasing with the introduction of new techniques, such as volumetric modulated arc therapy (VMAT). These new techniques offer superior conformity of high-dose regions to the target compared to conventional techniques, however more normal tissue is exposed to low-dose radiation with VMAT. There is a potential increase in radiobiological effectiveness associated with lower energy photons delivered during VMAT as normal cells are exposed to a temporal change in incident photon energy spectrum. During VMAT deliveries, normal cells can be exposed to the primary radiation beam, as well as to transmission and scatter radiation. The impact of low-dose radiation, radiation-induced bystander effect and change in energy spectrum on normal cells are not well understood. The current study examined cell survival and DNA damage in normal prostate cells after exposure to out-of-field radiation both with and without the transfer of bystander factors. The effect of a change in energy spectrum out-of-field compared to in-field was also investigated. Prostate cancer (LNCaP) and normal prostate (PNT1A) cells were placed in-field and out-of-field, respectively, with the PNT1A cells being located 1 cm from the field edge when in-field cells were being irradiated with 2 Gy. Clonogenic and γ-H2AX assays were performed postirradiation to examine cell survival and DNA damage. The assays were repeated when bystander factors from the LNCaP cells were transferred to the PNT1A cells and also when the PNT1A cells were irradiated in-field to a different energy spectrum. An average out-of-field dose of 10.8 ± 4.2 cGy produced a significant reduction in colony volume and increase in the number of γ-H2AX foci\\/cell in the PNT1A cells compared to the sham-irradiated control cells. An adaptive response was observed in the PNT1A cells having first received a low out-of-field dose and then the bystander factors. The PNT1A cells showed a significant

Ten-Year Survival Results of a Randomized Trial of Irradiation of Internal Mammary Nodes After Mastectomy

International Nuclear Information System (INIS)

Hennequin, Christophe; Bossard, Nadine; Servagi-Vernat, Stéphanie; Maingon, Philippe; Dubois, Jean-Bernard; Datchary, Jean; Carrie, Christian; Roullet, Bernard; Suchaud, Jean-Philippe; Teissier, Eric; Lucardi, Audrey; Gerard, Jean-Pierre; Belot, Aurélien

2013-01-01

Purpose: To evaluate the efficacy of irradiation of internal mammary nodes (IMN) on 10-year overall survival in breast cancer patients after mastectomy. Methods and Patients: This multicenter phase 3 study enrolled patients with positive axillary nodes (pN+) or central/medial tumors with or without pN+. Other inclusion criteria were age <75 and a Karnofsky index ≥70. All patients received postoperative irradiation of the chest wall and supraclavicular nodes and were randomly assigned to receive IMN irradiation or not. Randomization was stratified by tumor location (medial/central or lateral), axillary lymph node status, and adjuvant therapy (chemotherapy vs no chemotherapy). The prescribed dose of irradiation to the target volumes was 50 Gy or equivalent. The first 5 intercostal spaces were included in the IMN target volume, and two-thirds of the dose (31.5 Gy) was given by electrons. The primary outcome was overall survival at 10 years. Disease-free survival and toxicity were secondary outcomes. Results: T total of 1334 patients were analyzed after a median follow-up of 11.3 years among the survivors. No benefit of IMN irradiation on the overall survival could be demonstrated: the 10-year overall survival was 59.3% in the IMN-nonirradiated group versus 62.6% in the IMN-irradiated group (P=.8). According to stratification factors, we defined 6 subgroups (medial/central or lateral tumor, pN0 [only for medial/central] or pN+, and chemotherapy or not). In all these subgroups, IMN irradiation did not significantly improve overall survival. Conclusions: In patients treated with 2-dimensional techniques, we failed to demonstrate a survival benefit for IMN irradiation. This study cannot rule out a moderate benefit, especially with more modern, conformal techniques applied to a higher risk population

Inhibition of IL-1 activity induced with allogeneic transfusion of UV-irradiated blood

International Nuclear Information System (INIS)

Horvat, B.; Poljak-Blazi, M.; Hadija, M.

1991-01-01

Treatment with UV-irradiated donor-specific blood transfusion is known to induce specific unresponsiveness in recipient animals and prolong allograft survival. Mixed lymphocyte response in transfused mice was decreased towards spleen cells of the blood donor strain, but was not altered to third-party cells. Sera from treated mice showed significantly lower interleukin-1 (IL-1) activity, which was increased with higher dilutions of sera, indicating the presence of IL-1 inhibitor. Furthermore, sera decreased rIL-1-induced cell proliferation in dose-dependent manner, while the response to rIL-2 neither depended on the concentration of sera, nor differed between non-treated controls and treated mice. These results indicate that UV-irradiated allogeneic blood transfusion could induce an inhibitor, specifically directed to IL-1 activity, which may be involved in the generation of immunological unresponsiveness in treated animals. (author)

Genistein Protects Against Biomarkers of Delayed Lung Sequelae in Mice Surviving High-Dose Total Body Irradiation

Science.gov (United States)

DAY, Regina M.; BARSHISHAT-KUPPER, Michal; MOG, Steven R.; MCCART, Elizabeth A.; PRASANNA, P. G. S.; DAVIS, Thomas A.; LANDAUER, Michael R.

2008-01-01

The effects of genistein on 30-day survival and delayed lung injury were examined in C57BL/6J female mice. A single subcutaneous injection of vehicle (PEG-400) or genistein (200 mg/kg) was administered 24 h before total body irradiation (7.75 Gy 60Co, 0.6 Gy/min). Experimental groups were: No treatment + Sham (NC), Vehicle + Sham (VC), Genistein + Sham (GC), Radiation only (NR), Vehicle + Radiation (VR), Genistein + Radiation (GR). Thirty-day survivals after 7.75 Gy were: NR 23%, VR 53%, and GR 92%, indicating significant protection from acute radiation injury by genistein. Genistein also mitigated radiation-induced weight loss on days 13–28 postirradiation. First generation lung fibroblasts were analyzed for micronuclei 24 h postirradiation. Fibroblasts from the lungs of GR-treated mice had significantly reduced micronuclei compared with NR mice. Collagen deposition was examined by histochemical staining. At 90 days postirradiation one half of the untreated and vehicle irradiated mice had focal distributions of small collagen-rich plaques in the lungs, whereas all of the genistein-treated animals had morphologically normal lungs. Radiation reduced the expression of COX-2, transforming growth factor-β receptor (TGFβR) I and II at 90 days after irradiation. Genistein prevented the reduction in TGFβRI. However, by 180 days postirradiation, these proteins normalized in all groups. These results demonstrate that genistein protects against acute radiation-induced mortality in female mice and that GR-treated mice have reduced lung damage compared to NR or VR. These data suggest that genistein is protective against a range of radiation injuries. PMID:18434686

Genistein protects against biomarkers of delayed lung sequelae in mice surviving high-dose total body irradiation

International Nuclear Information System (INIS)

Day, R.M.; Barshishat-Kupper, M.; Mog, S.R.; Mccart, E.A.; Prasanna, P.G.S.; Landauer, M.R.; Davis, T.A.

2008-01-01

The effects of genistein on 30-day survival and delayed lung injury were examined in C57BL/6J female mice. A single subcutaneous injection of vehicle (PEG-400) or genistein (200 mg/kg) was administered 24 h before total body irradiation (7.75 Gy 60 Co, 0.6 Gy/min). Experimental groups were: No treatment+Sham (NC), Vehicle+Sham (VC), Genistein+Sham (GC), Radiation only (NR), Vehicle+Radiation (VR), Genistein+Radiation (GR). Thirty-day survivals after 7.75 Gy were: NR 23%, VR 53%, and GR 92%, indicating significant protection from acute radiation injury by genistein. Genistein also mitigated radiation-induced weight loss on days 13-28 postirradiation. First generation lung fibroblasts were analyzed for micronuclei 24 h postirradiation. Fibroblasts from the lungs of GR-treated mice had significantly reduced micronuclei compared with NR mice. Collagen deposition was examined by histochemical staining. At 90 days postirradiation one half of the untreated and vehicle irradiated mice had focal distributions of small collagen-rich plaques in the lungs, whereas all of the genistein-treated animals had morphologically normal lungs. Radiation reduced the expression of COX-2, transforming growth factor-β receptor (TGFβR) I and II at 90 days after irradiation. Genistein prevented the reduction in TGFβRI. However, by 180 days postirradiation, these proteins normalized in all groups. These results demonstrate that genistein protects against acute radiation-induced mortality in female mice and that GR-treated mice have reduced lung damage compared to NR or VR. These data suggest that genistein is protective against a range of radiation injuries. (author)

Local control and survival after external irradiation for adenocarcinoma of the prostate

International Nuclear Information System (INIS)

Rangala, N.; Cox, J.D.; Byhardt, R.W.; Wilson, J.F.; Greenberg, M.; Conceicao, A.L.D.

1982-01-01

From 1966 through 1978, 128 patients with biopsy-proven adenocarcinoma of the prostate underwent external irradiation to the entire pelvis followed by additional irradiation with a field that encompassed the entire prostate with generous margins. Local recurrence was diagnosed when palpable regrowth occurred and was confirmed by biopsy. Eighteen patients (14%) had local recurrence. Actuarial (life table) local recurrence rates, however, were 24% for both for Stage B and C patients. Actuarial five year survival was 100% for the 10 Stage A patients, 91% for the 25 Stage B, and 78% for the 93 Stage C patients. Actuarial five year disease-free survival was 59% for Stage B and 69% for Stage C patients. Local recurrence was affected by the total dose to the whole pelvis and the dose at the center of the prostate. Disease-free survival was influenced by differentiation. High dose external irradiation to the prostate and regional lymph nodes offers the greatest probability of long-term disease-free survival for patients with localized disease. Late bowel complications were seen in 14 patients (11%), two of whom required colostomies. Late urinary tract complications were observed in five patients (4%)

Hepatocyte growth factor protects human endothelial cells against advanced glycation end products-induced apoposis

International Nuclear Information System (INIS)

Zhou Yijun; Wang Jiahe; Zhang Jin

2006-01-01

Advanced glycation end products (AGEs) form by a non-enzymatic reaction between reducing sugars and biological proteins, which play an important role in the pathogenesis of atherosclerosis. In this study, we assessed AGEs effects on human umbilical vein endothelial cells (HUVECs) growth, proliferation and apoptosis. Additionally, we investigated whether hepatocyte growth factor (HGF), an anti-apoptotic factor for endothelial cells, prevents AGEs-induced apoptosis of HUVECs. HUVECs were treated with AGEs in the presence or absence of HGF. Treatment of HUVECs with AGEs changed cell morphology, decreased cell viability, and induced DNA fragmentation, leading to apoptosis. Apoptosis was induced by AGEs in a dose- and time-dependent fashion. AGEs markedly elevated Bax and decreased NF-κB, but not Bcl-2 expression. Additionally, AGEs significantly inhibited cell growth through a pro-apoptotic action involving caspase-3 and -9 activations in HUVECs. Most importantly, pretreatment with HGF protected against AGEs-induced cytotoxicity in the endothelial cells. HGF significantly promoted the expression of Bcl-2 and NF-κB, while decreasing the activities of caspase-3 and -9 without affecting Bax level. Our data suggest that AGEs induce apoptosis in endothelial cells. HGF effectively attenuate AGEs-induced endothelial cell apoptosis. These findings provide new perspectives in the role of HGF in cardiovascular disease

Gram-scale production of plasmid pUDK-HGF with current good manufacturing practices for gene therapy of critical limb ischemia.

Science.gov (United States)

Hu, ChunSheng; Cheng, XiaoChen; Lu, YuXin; Wu, ZuZe; Zhang, QingLin

2016-11-16

The demand of a plasmid encoding human hepatocyte growth factor gene (pUDK-HGF) in large quantities at high purity and concentration has increased for gene therapy of critical limb ischemia (CLI) in clinical trials. In this article, we produced pUDK-HGF in compliance with current good manufacturing practices at gram scale. The process included a 50-L batch fermentation, continuous alkaline lysis, and integrated three-step chromatography on Sepharose 6 Fast Flow, PlasmidSelect Xtra, and Source 15Q. The production process has been scaled up to yield 4.24 ± 0.41 g of pharmaceutical pUDK-HGF from 1.0 kg bacterial cell paste and the overall yield reached range from 58.37 to 66.70%. The final pUDK-HGF product exhibited high purity with supercoiled percentage of > 95.8% and undetectable residual RNA, contaminated protein, and bacterial endotoxin. The phase I clinical study indicates that intramuscular injection of pUDK-HGF is safe, well tolerated, and may provide symptomatic relief to CLI patients. These results show that our manufacturing process of pUDK-HGF is efficient in producing pharmaceutical-grade plasmid DNA and is safe for clinical applications.

Prolonged survival of isolated rat islet allografts pre-irradiated with X-rays

Energy Technology Data Exchange (ETDEWEB)

Kimura, Toshihisa; Note, Masayuki; Nakagawara, Gizo (Fukui Medical School, Matsuoka (Japan)); Kojima, Yasuhiko

1994-04-01

Prior to transplantation of islets, pre-incubation, or pre-irradiation may suppress the immunogenicity of islet cells without suppressing islet function. In the presently described experiments we investigated the use of X-ray irradiation prior to transplantation to reduce islet immunogenicity. To determine whether or not the islet function was reduced after irradiation, ACI rat islets were transplanted into the subrenal capsules of isogeneic rats which had been diabetic and examined the blood glucose level over a period of 40 days. The results indicated that irradiation injury was dose-dependent and that islets irradiated with over 80 Gy lost their function. Next, allogeneic transplantation was performed using the model of ACI rats to Lewis rats without the use of any immunosuppressive agent. Non-irradiated islets were rejected within 7 days. However 20 Gy or 40 Gy irradiated islets prolonged survival (18.7[+-]5.8 days (n=6) and 26.7[+-]10.0 days (n=6), respectively). To determine the basis for this effect, MHC expression of islets was examined by the immunoperoxidase technique. Immunohistologic studies showed that 40 Gy-irradiated islets were depleted of Class II antigen positive cells while Class I antigen expression was unchanged. These results suggest that the prolongation of islets survival by X-ray irradiation may possibly be due to, in part, the depletion of donor Class II antigen positive cells. (author).

Survival of embryo irradiated with gamma rays by embryo culture in Brassica pekinensis Rupr

International Nuclear Information System (INIS)

Moue, T.

1984-01-01

The effect of irradiation on the survival rates and embryonic development of Brassica pekinensis RUPR. (Varieties; Kashin, Kohai 65 nichi and kairyochitose) was investigated. The purpose of this study was to seek ways of increasing the survival rates of embryos such as B.oleracea obtained through embryo culture techniques after irradiation doses affecting seed fertility and germination, for the purpose of increasing mutation rates. Embryos at different developmental stages ranging from the globular to the early heart stages were irradiated with 20 KR of gamma rays at the daily rate 0L 20 KR or 10 KR (Fig.1 and Table 1). The embryos were excised from ovules 4 to 10 days after irradiation and cultured on White's medium. The shooting and rooting rates on the 34th day of culture were higher at the dose of 10 KR/day than 20 KR/day and were lower when the materials were irradiated at the young embryonic stage (Table 3). Varietal differences in the shooting and rooting rates were also observed. The irradiated embryos survived mainly in the state of callus. It was concluded that the embryo culture technique was successful when applied to irradiated embryos excised at the young embryonic stage and that the technique affected B.pekinensis less than B.oleracea

Skin Inqjuries Reduce Survival and Modulate Corticosterone, C-Reactive Protein, Complement Component 3, IgM, and Prostaglandin E2 after Whole-Body Reactor-Produced Mixed Field (n + γ-Photons Irradiation

Directory of Open Access Journals (Sweden)

Juliann G. Kiang

2013-01-01

Full Text Available Skin injuries such as wounds or burns following whole-body γ-irradiation (radiation combined injury (RCI increase mortality more than whole-body γ-irradiation alone. Wound-induced decreases in survival after irradiation are triggered by sustained activation of inducible nitric oxide synthase pathways, persistent alteration of cytokine homeostasis, and increased susceptibility to systemic bacterial infection. Among these factors, radiation-induced increases in interleukin-6 (IL-6 concentrations in serum were amplified by skin wound trauma. Herein, the IL-6-induced stress proteins including C-reactive protein (CRP, complement 3 (C3, immunoglobulin M (IgM, and prostaglandin E2 (PGE2 were evaluated after skin injuries given following a mixed radiation environment that might be found after a nuclear incident. In this report, mice received 3 Gy of reactor-produced mixed field (n+γ-photons radiations at 0.38 Gy/min followed by nonlethal skin wounding or burning. Both wounds and burns reduced survival and increased CRP, C3, and PGE2 in serum after radiation. Decreased IgM production along with an early rise in corticosterone followed by a subsequent decrease was noted for each RCI situation. These results suggest that RCI-induced alterations of corticosterone, CRP, C3, IgM, and PGE2 cause homeostatic imbalance and may contribute to reduced survival. Agents inhibiting these responses may prove to be therapeutic for RCI and improve related survival.

Matriptase is required for the active form of hepatocyte growth factor induced Met, focal adhesion kinase and protein kinase B activation on neural stem/progenitor cell motility.

Science.gov (United States)

Fang, Jung-Da; Lee, Sheau-Ling

2014-07-01

Hepatocyte growth factor (HGF) is a chemoattractant and inducer for neural stem/progenitor (NS/P) cell migration. Although the type II transmembrane serine protease, matriptase (MTP) is an activator of the latent HGF, MTP is indispensable on NS/P cell motility induced by the active form of HGF. This suggests that MTP's action on NS/P cell motility involves mechanisms other than proteolytic activation of HGF. In the present study, we investigate the role of MTP in HGF-stimulated signaling events. Using specific inhibitors of phosphatidylinositol-3-kinase (PI3K), protein kinase B (Akt) or focal adhesion kinase (FAK), we demonstrated that in NS/P cells HGF-activated c-Met induces PI3k-Akt signaling which then leads to FAK activation. This signaling pathway ultimately induces MMP2 expression and NS/P cell motility. Knocking down of MTP in NS/P cells with specific siRNA impaired HGF-stimulation of c-Met, Akt and FAK activation, blocked HGF-induced production of MMP2 and inhibited HGF-stimulated NS/P cell motility. MTP-knockdown NS/P cells cultured in the presence of recombinant protein of MTP protease domain or transfected with the full-length wild-type but not the protease-defected MTP restored HGF-responsive events in NS/P cells. In addition to functioning as HGF activator, our data revealed novel function of MTP on HGF-stimulated c-Met signaling activation. Copyright © 2014. Published by Elsevier B.V.

Improving the determination of irradiation efficacy by the identification of surviving bacteria from irradiated spices

International Nuclear Information System (INIS)

Koshikawa, Tomihiko; Matsushima, Masako; Hironiwa, Takayuki; Takekawa, Tetsuya; Miyahara, Makoto

2009-01-01

The identification of the surviving bacteria isolated from 5 kinds of irradiated spices (all-spice, oregano, sage, paprika and black pepper) was carried out to know whether these bacteria were marker organisms to determine the efficacy of the irradiation treatment. Except in paprika, B.megaterium was detected. In allspice, paprika and black pepper B.pumilus was detected. B.cereus was detected in allspice, oregano and black pepper. Gram negative bacteria such as Methylobacterium and Enterobacter genus were also detected in oregano, sage and paprika. These bacteria were strongly resistant to radiation, and can be used as marker organisms for the determination of the efficacy of the irradiation treatment of spices. (author)

Survival of mouse testicular stem cells after γ or neutron irradiation

International Nuclear Information System (INIS)

Lu, C.C.; Meistrich, M.L.; Thames, H.D. Jr.

1980-01-01

The survival of mouse testicular stem cells after γ or neutron irradiation was measured by counts of repopulated tubular cross sections and by the numbers of differentiated spermatogenic cells produced. The numbers of such cells were determined either by sperm head counts of the X-isozyme of lactate dehydrogenase enzyme levels. Qualitatively similar results were obtained with all three assays. The results have confirmed that, with C3H mice, stem-cell survival is higher when the γ-radiation dose is fractionated by a 24-h interval. Single-dose γ-radiaton survival curves for the stem cell had large shoulders and also showed the presence of a radioresistant subpopulation which predominated after doses greater than 600 rad. Part of the shoulder must have resulted from repair of sublethal damage since neutron irradiation produced survival curves with smaller shoulders. The relative biological effectiveness for stem-cell killing for these neutrons (mean energy, 22 MeV) varied from about 2.9 at 10 rad of γ radiation to 2.2 at 600 rad

Medium from X-rayed cultures induces DNA strand-breaks in non-irradiated HeLa cells

International Nuclear Information System (INIS)

Ikushima, T.; Okuyama, K.; Tanizaki, Y.

2002-01-01

There is growing evidence to indicate that several types of responses are induced by ionizing radiation in non-irradiated cells. Such bystander effects include the killing of non-irradiated cells, the induction of sister chromatid exchanges and chromosomal aberrations, and the induction of gene mutations and chromosomal instability and enhanced cell growth. In the present study, we assessed whether the medium from irradiated cultures can induce DNA strand-breaks in non-irradiated cells, using single-cell gel electrophoresis assay (comet assay). HeLa cells in culture were irradiated with 0.5 to 8 Gy of 140 kVp X-rays and one hour later, the medium was taken from the irradiated culture, passed through a filter and transferred to the parallel culture of non-irradiated HeLa cells as non-target cells. After incubation for 30 min, the comet assay was performed under alkaline and neutral conditions. Such treatments resulted in a dose-dependent increase in tail moment under either alkaline or neutral condition, indicating the induction of DNA single- or double-strand breaks, respectively. It was also shown that the clonogenic survival was reduced in the cells cultured in the medium from irradiated cultures. Such a change was not detected at all when medium alone was irradiated. These results provided disputed evidence that irradiated cells released certain genotoxic factor(s) into the culture medium that can induce DNA strand breaks leading to cell death. Our results suggest that physical contact between irradiated and non-irradiated cells may not be necessary for the bystander effects observed in this study. It appears that bystander responses may be mediated by multiple mechanisms

Cell survival in spheroids irradiated with heavy-ion beams

International Nuclear Information System (INIS)

Rodriguez, A.; Alpen, E.L.

1981-01-01

Biological investigations with accelerated heavy ions have been carried out regularly at the Lawrence Berkeley Laboratory Bevalac for the past four years. Most of the cellular investigations have been conducted on cell monolayer and suspension culture systems. The studies to date suggest that heavy charged particle beams may offer some radiotherapeutic advantages over conventional radiotherapy sources. The advantages are thought to lie primarily in an increased relative biological effectiveness (RBE), a decrease in the oxygen enhancement ratio (OER), and better tissue distribution dose. Experiments reported here were conducted with 400 MeV/amu carbon ions and 425 MeV/amu neon ions, using a rat brain gliosarcoma cell line grown as multicellular spheroids. Studies have been carried out with x-rays and high-energy carbon and neon ion beams. These studies evaluate high-LET (linear energy transfer) cell survival in terms of RBE and the possible contributions of intercellular communication. Comparisons were made of the post-irradiation survival characteristics for cells irradiated as multicellular spheroids (approximately 100 μm and 300 μm diameters) and for cells irradiated in suspension. These comparisons were made between 225-kVp x-rays, 400 MeV/amu carbon ions, and 425 MeV/amu neon ions

Naked gene therapy of hepatocyte growth factor for dextran sulfate sodium-induced colitis in mice

International Nuclear Information System (INIS)

Kanbe, Takamasa; Murai, Rie; Mukoyama, Tomoyuki; Murawaki, Yoshiyuki; Hashiguchi, Ko-ichi; Yoshida, Yoko; Tsuchiya, Hiroyuki; Kurimasa, Akihiro; Harada, Ken-ichi; Yashima, Kazuo; Nishimuki, Eiji; Shabana, Noriko; Kishimoto, Yukihiro; Kojyo, Haruhiko; Miura, Kunihiko; Murawaki, Yoshikazu; Kawasaki, Hironaka; Shiota, Goshi

2006-01-01

Ulcerative colitis (UC) is progressive and relapsing disease. To explore the therapeutic effects of naked gene therapy of hepatocyte growth factor (HGF) on UC, the SRα promoter driving HGF gene was intrarectally administered to the mice in which colitis was induced by dextran sulfate sodium (DSS). Expression of the transgene was seen in surface epithelium, lamina propria, and muscularis mucosae. The HGF-treated mice showed reduced colonic mucosal damage and increased body weights, compared with control mice (P < 0.01 and P < 0.05, respectively). The HGF-treated mice displayed increased number of PCNA-positive cells and decreased number of apoptotic cells than in control mice (P < 0.01, each). Phosphorylated AKT was dramatically increased after HGF gene administration, however, phosphorylated ERK1/2 was not altered. Microarray analysis revealed that HGF induced expression of proliferation- and apoptosis-associated genes. These data suggest that naked HGF gene delivery causes therapeutic effects through regulation of many downstream genes

Prolongation of rat islet allograft survival by direct ultraviolet irradiation of the graft

International Nuclear Information System (INIS)

Lau, H.; Reemtsma, K.; Hardy, M.A.

1984-01-01

Ultraviolet irradiation of rat dendritic cells completely abrogated their allostimulatory capacity in a mixed lymphocyte reaction. Rat islets of Langerhans similarly irradiated remained hormonally functional when transplanted into syngeneic diabetic rats. Allogeneic transplantation across a major histocompatibility barrier of islets initially treated in vitro with ultraviolet irradiation resulted in prolonged allograft survival without the use of any immunosuppressive agents

Semi-synthesis of a HGF/SF kringle one (K1) domain scaffold generates a potent in vivo MET receptor agonist.

Science.gov (United States)

Simonneau, Claire; Bérénice Leclercq; Mougel, Alexandra; Adriaenssens, Eric; Paquet, Charlotte; Raibaut, Laurent; Ollivier, Nathalie; Drobecq, Hervé; Marcoux, Julien; Cianférani, Sarah; Tulasne, David; de Jonge, Hugo; Melnyk, Oleg; Vicogne, Jérôme

2015-03-01

The development of MET receptor agonists is an important goal in regenerative medicine, but is limited by the complexity and incomplete understanding of its interaction with HGF/SF (Hepatocyte Growth Factor/Scatter Factor). NK1 is a natural occurring agonist comprising the N-terminal (N) and the first kringle (K1) domains of HGF/SF. In the presence of heparin, NK1 can self-associate into a "head to tail" dimer which is considered as the minimal structural module able to trigger MET dimerization and activation whereas isolated K1 and N domains showed a weak or a complete lack of agonistic activity respectively. Starting from these structural and biological observations, we investigated whether it was possible to recapitulate the biological properties of NK1 using a new molecular architecture of isolated N or K1 domains. Therefore, we engineered multivalent N or K1 scaffolds by combining synthetic and homogeneous site-specifically biotinylated N and K1 domains (NB and K1B) and streptavidin (S). NB alone or in complex failed to activate MET signaling and to trigger cellular phenotypes. Importantly and to the contrary of K1B alone, the semi-synthetic K1B/S complex mimicked NK1 MET agonist activity in cell scattering, morphogenesis and survival phenotypic assays. Impressively, K1B/S complex stimulated in vivo angiogenesis and, when injected in mice, protected the liver against fulminant hepatitis in a MET dependent manner whereas NK1 and HGF were substantially less potent. These data reveal that without N domain, proper multimerization of K1 domain is a promising strategy for the rational design of powerful MET agonists.

The effect of natural hot environment on survival and peripheral blood lymphocytes in γ-irradiated mice

International Nuclear Information System (INIS)

Zhou Meijuan; Zheng Li; Ding Zhenhua

2004-01-01

Objective: To study the effect of natural hot environment (NHE) on survival and peripheral blood lymphocytes in γ-irradiated in mice. Methods: After γ-irradiation at the dosage of 6.5 or 9.0 Gy, the mice were exposed to NHE for 0, 3, 6, 9 h or 30 days. After exposure to NHE, mice of the 6 h and 9 h groups, were then bred at room temperature. The survival and peripheral blood lymphocytes were observed for 30 days. Results: There were obvious differences in survival time between the groups that were exposed to NHE for 9 h and 30 d and that of the 0 h group, the mice of these three groups having been irradiated with 6.5 Gy. For 9.0 Gy-irradiated mice, the survival times of the 6, 9 h and 30 d groups were all significantly shorter than that of the 0 h group. The descending rate of peripheral blood lymphocytes in 0 h group is smaller than that of all NHE groups. There was no lymphocyte fluctuate resuscitation in all NHE groups as seen in the 0 h group. Conclusion: There is a significant decrease of survival indexes and a faster descending rate of peripheral blood lymphocytes in mice exposed to after γ-irradiation. (authors)

Long-term survival of skin allografts in mice treated with fractionated total lymphoid irradiation

International Nuclear Information System (INIS)

Slavin, S.; Strober, S.; Fuks, Z.; Kaplan, H.S.

1976-01-01

Treatment of recipient Balb/c mice with fractionated, high-dose total lymphoid irradiation, a procedure commonly used in the therapy of human malignant lymphomas, resulted in fivefold prolongation of the survival of C57BL/Ka skin allografts despite major histocompatibility differences between the strains (H-2/sup d/ and H-2/sup b/, respectively). Infusion of 10 7 (C57BL/Ka x Balb/c)F 1 bone marrow cells after total lymphoid irradiation further prolonged C57BL/Ka skin graft survival to more than 120 days. Total lymphoid irradiation may eventually prove useful in clinical organ transplantation

Influence of locoregional irradiation on local control and survival in breast cancer

International Nuclear Information System (INIS)

Cutuli, B.

1998-01-01

Locoregional control is a crucial step in the achievement of breast cancer cure. In ductal carcinoma in situ, breast irradiation significantly reduces the rates of local recurrence whatever the histological subtypes, as demonstrated by the NSABP-B17 trial (25.8 % of local recurrences without radiotherapy vs. 11.4 % with radiotherapy). In infiltrating breast carcinomas, complementary breast irradiation has been shown to significantly improve the local control and slightly the overall survival in five randomized trials. Following mastectomy, locoregional irradiation clearly reduces the chest wall and nodal relapse rates, especially in case of lesions more than 5 cm or with nodal involvement and/or large lymphatic or vascular emboli. Two recent randomized trials confirmed the benefit of well-adapted locoregional irradiation in all subgroups, especially in patients with one to three axillary involves nodes. In the Danish trial (including pre-menopausal high-risk women), radiotherapy reduced locoregional relapses from 32 to 9 % (p<0.001) and increased the 10-year survival rate from 45 to 54% (p<0.001). In the Canadian trial, locoregional relapse rate decreased from 25 to 13 % and the 10-year survival rate increased from 56 to 65 %. The meta-analysis published in 1995 by the EBCTCG showed only a modest benefit due to locoregional irradiation in breast cancer. However, when small or old trials were excluded due to imperfect methodology or inadequate irradiation techniques, the benefit of modern radiotherapy became much more evident in a population of 7,840 patients. Locoregional irradiation appears to be able to reduce the risk of metastatic evolution occurring after local or nodal relapse and must be integrated in a multidisciplinary strategy. Treatment toxicity (especially toxicity due to irradiation of internal mammary nodes) is of special concern, as anthracycline-based chemotherapy is prescribed more often. The use of a direct field, with at least 60 % of the dose

Quantitative analysis of HGF and EGF-dependent phosphotyrosine signaling networks

DEFF Research Database (Denmark)

Hammond, Dean E; Hyde, Russell; Kratchmarova, Irina

2010-01-01

549 lung adenocarcinoma cells with EGF or HGF. In total, we obtained quantitative information for 274 proteins, which respond to either or both stimuli by >1.5 fold changes in enrichment, following immuno-precipitation with antiphosphotyrosine antibodies. The data reveal a high degree of overlap...

Irradiation induced effects in zirconium (A review)

International Nuclear Information System (INIS)

Madden, P.K.

1975-06-01

Irradiation creep in zirconium and its alloys is comprehensively discussed. The main theories are outlined and the gaps between them and the observed creep behaviour, indicated. Although irradiation induced point defects play an important role, effects due to irradiation induced dislocation loops seem insignificant. The experimental results suggest that microstructural variations due to prior cold-working or hydrogen injection perturb the irradiation growth and the irradiation creep of zircaloy. Further investigations into these areas are required. One disadvantage of creep experiments lies in their duration. The possibility of accelerated experiments using ion implantation or electron irradiation is examined in the final section, and its possible advantages and disadvantages are outlined. (author)

Sexual Competitiveness, Field Survival, and Dispersal of Anastrepha obliqua (Diptera: Tephritidae) Fruit Flies Irradiated at Different Doses.

Science.gov (United States)

Gallardo-Ortiz, Uriel; Pérez-Staples, Diana; Liedo, Pablo; Toledo, Jorge

2018-04-02

The sterile insect technique (SIT) is used in area-wide pest management programs for establishing low pest prevalence and/or areas free of fruit flies (Diptera: Tephritidae). The aim of this technique is to induce high levels of sterility in the wild population, for this the released insects must have a high sexual competitiveness and field dispersal. However, radiation decreases these biological attributes that do not allow it to compete successfully with wild insects. In this study the sexual competitiveness, field survival and dispersal of Anastrepha obliqua (Macquart; Diptera: Tephritidae) irradiated at 0, 40, 50, 60, 70, and 80 Gy were evaluated in laboratory. A dose of 60 Gy produced 98% sterility, whereas doses of 70 and 80 Gy produced 99% sterility. Sexual competitiveness was assessed in field cages, comparing males irradiated at 0, 50, 60, 70, and 80 Gy against wild males for mating with wild fertile females. Males irradiated at 50 and 60 Gy achieved more matings than those irradiated at 70 and 80 Gy. Wild males were more competitive than mass-reared males, even when these were not irradiated (0 Gy). There was no effect of irradiation on mating latency, yet wild males showed significantly shorter mating latency than mass-reared males. Female remating did not differ among those that mated with wild males and those that mated with males irradiated with different doses. The relative sterility index (RSI) increased from 0.25 at 80 Gy to 0.37 at 60 Gy. The Fried competitiveness index was 0.69 for males irradiated at 70 Gy and 0.57 for those irradiated at 80 Gy, which indicates that a 10 Gy reduction in the irradiation dose produces greater induction of sterility in the wild population. There were no significant differences in field survival and dispersal between flies irradiated at 70 or 80 Gy. Reducing the irradiation dose to 60 or 70 Gy could improve the performance of sterile males and the effectiveness of the SIT. Our results also distinguish between the

Gamma irradiation-induced variation in carrots (Daucus carota L.)

International Nuclear Information System (INIS)

Al-Safadi, B.; Simon, P.W.

1996-01-01

Carrot tissue cultures, germinating seed, and dry seed were exposed to gamma radiation. Irradiation accelerated germination of carrot seed in the M1 generation at low doses (0.5 and 1 krad), whereas higher doses delayed germination. A high negative correlation was observed between dose and survival of plants after seed irradiation. Plant size and root weight were 20% to 35% greater than control plants after seeds, but not tissue cultures, were exposed to low doses of gamma irradiation. Higher doses reduced M1 plant size by 50% in germinating seed and tissue culture treatments but less for the dry seed treatment. Seed production decreased while phenotypic variation of M1 plants increased with increasing gamma ray dosage. Root weight and total dissolved solids were highly variable in M2 families. Less variation was observed in total carotene content and none was seen in sugar type (reducing vs. non reducing sugars). Induced variation in root color and root shape was also observed. Irradiation of germinating seed and tissue cultures yielded more M2 variation than irradiation of dry seed. Putative point mutations were not observed. Unirradiated carrot tissue cultures did not yield significant M2 somaclonal variation. Average root weight of M2 plants increased with increasing gamma ray dosage, especially for the dry seed treatment

Gamma irradiation induced variation in carrots (Daucus Carota L.)

International Nuclear Information System (INIS)

Al-Safady, B.; Simon, P.W.

1999-01-01

Carrot tissue cultures, germinating seed, and dry seed were exposed to gamma radiation. Irradiation accelerated germination of carrot seed in the M 1 generation at low doses (0.5 and 1 krad), whereas higher doses delayed germination. A high negative correlation was observed between dose and survival of plants after seed irradiation. Plant size and root weight were 20% to 35% greater than control plants after seeds, but not tissue culture, were exposed to low doses of gamma irradiation. Higher doses reduced M 1 plant size by > 50% in germinating seed and tissue culture treatments but less for the dry seed treatment. Seed production decreased while phenotypic variation of M 1 plants increased with increasing gamma ray dosage. Root weight and total dissolved solids were highly variable in M 2 families. Less variation was observed in total carotene content and none was seen in sugar type [reducing vs. non reducing sugars]. Induced variation in root color and rot shape was also observed. Irradiation of germinating seed and tissue cultures yielded more M 2 variation than irradiation of dry seed. Putative point mutations were not observed. Unirradiated carrot tissue cultures did not yield significant M 2 somaclonal variation. Average root weight of M 2 plants increased with increasing gamma ray dosage, especially for the dry seed treatment (Author)

The regulatory role of heparin on c-Met signaling in hepatocellular carcinoma cells.

Science.gov (United States)

İşcan, Evin; Güneş, Aysim; Korhan, Peyda; Yılmaz, Yeliz; Erdal, Esra; Atabey, Neşe

2017-06-01

The role of heparin as an anticoagulant is well defined; however, its role in tumorigenesis and tumor progression is not clear yet. Some studies have shown that anticoagulant treatment in cancer patients improve overall survival, however, recent clinical trials have not shown a survival benefit in cancer patients receiving heparin treatment. In our previous studies we have shown the inhibitory effects of heparin on Hepatocyte Growth Factor (HGF)-induced invasion and migration in hepatocellular carcinoma (HCC) cells. In this study, we showed the differential effects of heparin on the behaviors of HCC cells based on the presence or absence of HGF. In the absence of HGF, heparin activated HGF/c-Met signaling and promoted motility and invasion in HCC cells. Heparin treatment led to c-Met receptor dimerization and activated c-Met signaling in an HGF independent manner. Heparin-induced c-Met activation increased migration and invasion through ERK1/2, early growth response factor 1 (EGR1) and Matrix Metalloproteinases (MMP) axis. Interestingly, heparin modestly decreased the proliferation of HCC cells by inhibiting activatory phosphorylation of Akt. The inhibition of c-Met signaling reversed heparin-induced increase in motility and invasion and, proliferation inhibition. Our study provides a new perspective into the role of heparin on c-Met signaling in HCC.

Effects of irradiation on the survival of bacterial contaminants in food

Directory of Open Access Journals (Sweden)

Lily Natalia

2016-01-01

Full Text Available The primary concern about microbial safety of irradiated food is the survival of pathogenic spore forming bacteria. Clostridium sporogenes was selected as the spore forming test organism for conducting inoculated pack studies for its similarities to the most toxigenic Cl. botulinum, in radiation resistance. Minimum radiation dose applied (45 kGy under cryogenic condition, in -790C was determined to eliminate Cl. sporogenes spores and other bacterial contaminants in different kind of Indonesian chicken and beef dishes. In separate studies, irradiation doses of 3 – 7 kGy at cryogenic condition was used to improve the microbiological safety of a number chilled prepared meals. The dishes or ready to eat foods were packaged in air impermeable pouches. Irradiation process was carried out after inoculation on chicken and beef dishes with certain amounts of Cl. sporogenes spores. The evaluation of colony count differences between the irradiated and unirradiated foods revealed the effect of radiation on the survival of bacterial spores or other bacterial contaminants. It was demonstrated that a minimum dose of 45 kGy under cryogenic condition eliminated the spore of Cl. sporogenes, Bacillus spp and Staphylococcus spp. Irradiation at doses 5-7 kGy significantly reduced some potential pathogenic microorganisms in samples without affecting quality up to 3 months of storage at the refrigeration temperature.

IR-induced autophagy plays a role in survival of HeLa cells

International Nuclear Information System (INIS)

Kang, Mi Young; Jang, Eun Yeong; Ryu, Tae Ho; Chung, Dong Min; Kim, Jin Hong; Kim, Jin Kyu

2014-01-01

Cells respond to stress with repair, or are diverted into irreversible cell cycle exit (senescence) or are eliminated through programmed cell death. There are two major morphologically distinctive forms of programmed cell death, apoptosis and autophagic cell death. Apoptosis contribute to cell death, whereas autophagy can play a dual role in mediating either cell survival or death in response to various stress stimuli. Here we analysed cellular responses induced by IR. The understanding of an appropriate cellular stress response is of crucial importance in foreseeing the cell fate. Apoptotic feagures were not detected in HeLa under our experimental irradiation condition. Autophagic cell death in HeLa may play an important role in cell protection and can result in cell survival

A reevaluation of X-irradiation-induced phocomelia and proximodistal limb patterning.

Science.gov (United States)

Galloway, Jenna L; Delgado, Irene; Ros, Maria A; Tabin, Clifford J

2009-07-16

Phocomelia is a devastating, rare congenital limb malformation in which the long bones are shorter than normal, with the upper portion of the limb being most severely affected. In extreme cases, the hands or fingers are attached directly to the shoulder and the most proximal elements (those closest to the shoulder) are entirely missing. This disorder, previously known in both autosomal recessive and sporadic forms, showed a marked increase in incidence in the early 1960s due to the tragic toxicological effects of the drug thalidomide, which had been prescribed as a mild sedative. This human birth defect is mimicked in developing chick limb buds exposed to X-irradiation. Both X-irradiation and thalidomide-induced phocomelia have been interpreted as patterning defects in the context of the progress zone model, which states that a cell's proximodistal identity is determined by the length of time spent in a distal limb region termed the 'progress zone'. Indeed, studies of X-irradiation-induced phocomelia have served as one of the two major experimental lines of evidence supporting the validity of the progress zone model. Here, using a combination of molecular analysis and lineage tracing in chick, we show that X-irradiation-induced phocomelia is fundamentally not a patterning defect, but rather results from a time-dependent loss of skeletal progenitors. Because skeletal condensation proceeds from the shoulder to fingers (in a proximal to distal direction), the proximal elements are differentially affected in limb buds exposed to radiation at early stages. This conclusion changes the framework for considering the effect of thalidomide and other forms of phocomelia, suggesting the possibility that the aetiology lies not in a defect in the patterning process, but rather in progenitor cell survival and differentiation. Moreover, molecular evidence that proximodistal patterning is unaffected after X-irradiation does not support the predictions of the progress zone model.

Rat mammary-cell survival following irradiation with 14.3-MeV neutrons

International Nuclear Information System (INIS)

Mahler, P.A.; Gould, M.N.; DeLuca, P.M. Jr.; Pearson, D.W.; Clifton, K.H.

1982-01-01

The survival of rat mammary gland cells irradiated in situ with either single or split doses of 14.3-MeV neutrons was determined by an in vivo transplantation assay. The single-dose data are best fit to the multitarget single-hit model by the parameters D 0 = 97 cGy and n = 0.6 while the split-dose data are best fit by the parameters D 0 = 100 cGy and n = 1.2. Analysis of the combined data sets suggests that the two survival curves are not identical. Comparison of these data with previously published results following irradiation with 250-kVp x-rays is reported

Rat mammary cell survival following irradiation with 14.3-MeV neutrons

International Nuclear Information System (INIS)

Mahler, P.A.; Gould, M.N.; DeLuca, P.M. Jr.; Pearson, D.W.; Clifton, K.H.

1982-01-01

The survival of rat mammary gland cells irradiated in situ with either single or split doses of 14.3-MeV neutrons was determined by an in vivo transplantation assay. The single-dose data are best fit to the multitarget single-hit model by the parameters D/sub o/ = 97 cGy and n = 0.6 while the split-dose data are best fit by the parameters D/sub o/ = 100 cGy and n = 1.2.Analysis of the combined data sets suggests that the two survival curves are not identical. Comparison of these data with previously published results following irradiation with 250-kVp X rays is reported

Total lymphoid irradiation

International Nuclear Information System (INIS)

Sutherland, D.E.; Ferguson, R.M.; Simmons, R.L.; Kim, T.H.; Slavin, S.; Najarian, J.S.

1983-01-01

Total lymphoid irradiation by itself can produce sufficient immunosuppression to prolong the survival of a variety of organ allografts in experimental animals. The degree of prolongation is dose-dependent and is limited by the toxicity that occurs with higher doses. Total lymphoid irradiation is more effective before transplantation than after, but when used after transplantation can be combined with pharmacologic immunosuppression to achieve a positive effect. In some animal models, total lymphoid irradiation induces an environment in which fully allogeneic bone marrow will engraft and induce permanent chimerism in the recipients who are then tolerant to organ allografts from the donor strain. If total lymphoid irradiation is ever to have clinical applicability on a large scale, it would seem that it would have to be under circumstances in which tolerance can be induced. However, in some animal models graft-versus-host disease occurs following bone marrow transplantation, and methods to obviate its occurrence probably will be needed if this approach is to be applied clinically. In recent years, patient and graft survival rates in renal allograft recipients treated with conventional immunosuppression have improved considerably, and thus the impetus to utilize total lymphoid irradiation for its immunosuppressive effect alone is less compelling. The future of total lymphoid irradiation probably lies in devising protocols in which maintenance immunosuppression can be eliminated, or nearly eliminated, altogether. Such protocols are effective in rodents. Whether they can be applied to clinical transplantation remains to be seen

Long-term survival in nasopharyngeal carcinoma and late complications of irradiation

International Nuclear Information System (INIS)

Furukawa, Mitsuru; Komori, Takashi; Ishiguro, Hideyo; Takimoto, Toru; Umeda, Ryozo

1983-01-01

Irradiation remains the mainstay of treatment of nasopharyngeal carcinoma in the primary site and the neck. We studied the long-term effects of irradiation in five patients who have survived ten or more years after treatment without recurrence of disease, and we were impressed by the rarity of disabling complications of the treatment. Minor complications were common, and especially troublesome were xerostomia, dental caries, postnasal crusting and neck weakness. (author)

Biochemical aspects of the immunomodular action in irradiated survival mice with 60C gama irradiation

International Nuclear Information System (INIS)

Garcia Agudo, N.L. del M. de.

1983-01-01

The radioprotective action of Calmetti-Guerin bacillus (BCG), Corynebacterium parvum, Escherichia coli Lipopolysccharides (LPS) and peptone proteose was evaluated. A single injection of the macrophage activiting agents prior to 60 Co whole-body irradiation increased the survival rate of mice in the lethal dose range. (L.M.J.) [pt

Proliferation and clonal survival of human lung cancer cells treated with fractionated irradiation in combination with paclitaxel

International Nuclear Information System (INIS)

Rijn, Johannes van; Berg, Jaap van den; Meijer, Otto W.M.

1995-01-01

Purpose: This study was performed to determine the effects of a continuous exposure to paclitaxel (taxol) in combination with fractionated irradiation on cell proliferation and survival. Methods and Materials: Human lung carcinoma cells (SW1573) were given a daily treatment with 3 Gy of x-rays during 5 days in the continuous presence of 5 nM taxol. The surviving fraction and the total number of cells were determined every 24 h before and immediately after irradiation. Results: Irradiation with 5 x 3 Gy and 5 nM taxol cause approximately the same inhibition of cell proliferation. In combination these treatments have an additional effect and the cell population increases no further after the first 24 h. Whereas the cells become more resistant to taxol after the first 24 h with a minimum survival of 42%, taxol progressively reduces the population of surviving cells in combination with x-rays when the number of fractions increases, up to 25-fold relative to irradiation alone. The enhancement effect of 5 nM taxol is likely to be attributed to an inhibition of the repopulation during fractionated irradiation and not to an increased radiosensitivity. Only after treatment with 10 or 100 nM taxol for 24 h, which is attended with a high cytotoxicity, is moderate radiosensitization observed. Conclusion: Taxol, continuously present at a low concentration with little cytotoxicity, causes a progressive reduction of the surviving cell population in combination with fractionated irradiation, mainly by an inhibition of the repopulation of surviving cells between the dose fractions

The influence of scrotonin on survival of Candida guillermondii, irradiated by short-wave ultraviolet

International Nuclear Information System (INIS)

Strakhovskaya, M.G.; Frajkin, G.Ya.; Goncharenko, E.N.

1982-01-01

A study was made on the influence of serotonin on survival of Candida quilliermondu yeast irradiated by 254 nm short-wave ultraviolet. It was established that incubation with serotonin, leading to its penetration inside cells causes two opposite effects - protection from ultraviolet inactivation in preliminary incubation and intensification of cells death in postradiation incubation. Serotonin action is similar to the effects induced in C. guillermondii yeast by 334 nm long-wave ultraviolet light, that is serotonin possesses photomimetic effect. The data obtained are considered as conformaition of participation of serotonin photoinduced synthesis in manifestation of effects of long-wave ultraviolet light action on yeast

The effects of pentoxifylline on the survival of human glioma cells with continuous and intermittent stereotactic radiosurgery irradiation

International Nuclear Information System (INIS)

Eley, Kerry W.; Benedict, Stanley H.; Chung, Theodore D.K.; Kavanagh, Brian D.; Broaddus, William C.; Schmidt-Ullrich, Rupert K.A.; Lin, P.-S.

2002-01-01

Purpose: In linac-based stereotactic radiosurgery, treatment is delivered intermittently via multiple individual small radiotherapy arcs. The time lapses between the individual arcs permit greater damage repair and increased tumor cell survival in comparison with continuous irradiation. Because pentoxifylline (PTX) has been reported to prevent radiation-induced cell cycle arrest at the G2/M checkpoint, where damage repair is critically linked to cell survival, we hypothesized that PTX would exert a favorable radiosensitization effect by reducing the recovery observed during intermittent stereotactic radiosurgery. Methods and Materials: The human glioma cell line T98G was used to study the effects of continuous vs. intermittent irradiation with or without PTX. Cell cycle patterns were studied using flow cytometry. Clonogenic assays of single cells and spheroid outgrowth assays provided a quantitative measure of PTX-mediated radiosensitization. The PTX effect upon cells in low oxygen conditions was also studied in vitro after enzymatic oxygen scavenging. Results: Flow Cytometry: T98G cells exposed to both continuous and intermittent irradiation exhibit similar arrest at the G2/M checkpoint. The addition of 2 mM PTX significantly reduced the radiation-induced G2/M block in both irradiation schemes. Clonogenic Assays: The same PTX concentration applied before a continuous dose of 12 Gy, two intermittent doses of 6 Gy, or three intermittent doses of 4 Gy, all given within a 1-h interval, consistently caused radiosensitization. The drug enhancement ratios for PTX were 1.5, 2.7, and 6.0 for the continuous and two different intermittent dose schedules, respectively. Adding PTX after irradiation yielded lower enhancement ratios than pre-irradiation application. A similar pattern was observed after total doses of 4, 6, 9, or 12 Gy, as well. In low oxygen conditions, PTX was seen to have the same effects as in normoxic conditions. Spheroid Outgrowth Assays: The in vitro PTX

Effect of the irradiation of bacteria upon their survival rate during conventional methods of meat preservation

International Nuclear Information System (INIS)

Szczawinska, M.

1981-01-01

The purpose of this paper is to define the effect of irradiation upon the survival rate of non-sporing bacteria (Staphylococcus aureus, Salmonella typhimurium, Escherichia coli, Pseudomonas fluorescens) during basic methods of meat preservation. The bacteria were irradiated in broth by X-rays at a dose that destroyed about 90% of the bacteria (D 10 ). The survival rate of unirradiated and irradiated bacteria during cooling and freezing, in solutions of sodium chloride, nitrates and liquid smoke, was defined. The number of microorganisms was determined directly after irradiation as well as 1, 3, 7, 14, 21 and 28 days after irradiation. The effect of irradiation upon heat resistance of the examined species of bacteria was also defined. The microorganisms were heated in broth, at 70 0 C for 1, 2 and 5 minutes. The obtained results were subjected to statistical analysis. On the basis of the research results, a faster dying rate of irradiated populations of S. aureus and E. coli during any type of preservation treatment, the lack of any reaction to irradiation regarding the survival rate of S. typhimurium, and the lack of any effect of irradiation upon the rate of deterioration of P. fluorescens during freezing and storage in a solution with 10% addition of NaCI, were observed. On the other hand, a pronounced effect of irradiation upon the lowering of the heat resistance of the bacteria, as well as delayed growth in other variants of the experiment, was determined. (author)

Study on cytotoxicities induced by alpha particle irradiation combined with NNK treatment

International Nuclear Information System (INIS)

Li Ping; Yang Zhihua; Pan Xiujie; Cao Zhenshan; Mi Na; Chen Zhongmin; Liu Gang; Wei Han; Li Huiyin; Zhu Maoxiang

2006-01-01

Objective: To investigate cytotoxicities of alpha-particle irradiation combined with NNK treatment. Methods: Exponentially growing immortalized human bronchial epithelial cells were divided into normal control group (NC), alpha particle irradiation group (α), NNK administration group (NNK), NNK administration (100 μg/ml) followed by alpha particle irradiation group (NNK + α), and alphaparticle irradiation followed by NNK administration (100 μg/ml) group (α + NNK). Cell survival fractions were measured by cloning rate of low-density plating cell. Ethidium bromide and 2', 7'-dichlorofluorescein, fluorescent products of the membrane-permeable dyes hydroethine and 2', 7'-dichloroflurescindiacetate were used to monitor the inarticulate reactive oxygen species (ROS) . Damage to membrane permeability was evaluated through testing LDH activity in medium. Results: In the groups exposed to both alpha particles and NNK, the survival rates were significantly lower than that of the groups administrated with the same dose of alpha particles or NNK alone. The levels of intracellular ROS and the activity of LDH in medium were significantly higher than that of the groups administrated with the same dose of alpha particles or NNK alone. Subtracted the NNK effect, the survival rates of the groups received both alpha particle irradiation and NNK treatment were significantly lower than that of alpha particle irradiated only group. However, the intracellular ROS level and the activity of LDH in medium were significantly higher than that of alpha-particle irradiated only group. In addition, the survival rates of the cells in groups exposed to alpha particle irradiation followed by NNK administration were significantly lower than that of cells treated with NNK administration followed by alpha particle irradiation. Conclusions: Alpha particle irradiation and NNK administration had synergisticity in cytotoxicity, and furthermore different schedules of the administration resulted in

Effect of fibrinolysis inhibitors on survival time of irradiated rats

International Nuclear Information System (INIS)

Smok, W.

1988-01-01

The possibilities of alleviation of the gastrointestinal syndrome of acute radiation sickness by modification of haemorrhagic diathesis using EACA and traskolan were studied. A significant prolongation of the mean survival time was obtained in the irradiated rats treated with EACA. 7 tabs., 10 refs. (author)

Action of caffeine on the survival of x-irradiated cells

International Nuclear Information System (INIS)

Busse, P.M.

1978-01-01

Post-irradiation treatment of HeLa S3 cells with 1 mM caffeine results in a marked diminution of the surviving fraction as scored by colony formation. The decrease is dose-dependent; the effect of a 24-h post-irradiation treatment of a non-synchronous population with caffeine is to change the terminal slope of the survival curve and its intercept. Do is reduced from 130 to 60 rad; the extrapolation number is increased about twofold. The amount of post-irradiation killing is maximal if cells are exposed to caffeine at a concentration of at least 1 mM for 8 hours; less than 10% of unirradiated cells are killed under these conditions. Dose-response curves were also obtained for synchronous cells at various phases of the cell cycle. Similar results were obtained at all cell ages, but the magnitude of the effect is age-dependent. This age dependence was further explored in experiments in which mitotically collected cells were exposed to 300 or 500 rad doses at 2-hour intervals throughout the cell cycle. Treatment with caffeine for 24 hours after irradiation enhances the killing of cells late in the cycle more than in G 1 . The sensitivities of two other cell lines, CHO and EMT6, also were examined; both are substantially less sensitive to caffeine. The smaller cell-cycle dependence of CHO cells is qualitatively the same as that of HeLa cells

Overview of Radiosensitivity of Human Tumor Cells to Low-Dose-Rate Irradiation

International Nuclear Information System (INIS)

Williams, Jerry R.; Zhang Yonggang; Zhou Haoming; Gridley, Daila S.; Koch, Cameron J.; Slater, James M.; Little, John B.

2008-01-01

Purpose: We compared clonogenic survival in 27 human tumor cell lines that vary in genotype after low-dose-rate (LDR) or high-dose rate (HDR) irradiation. We measured susceptibility to LDR-induced redistribution in the cell cycle in eight of these cell lines. Methods and Materials: We measured clonogenic survival after up to 96 hours of LDR (0.25 Gy/h) irradiation. We compared these with clonogenic survival after HDR irradiation (50 Gy/h). Using flow cytometry, we measured LDR-induced redistribution as a function of time during LDR irradiation in eight of these cell lines. Results: Coefficients that describe clonogenic survival after both LDR and HDR irradiation segregate into four radiosensitivity groups that associate with cell genotype: mutant (mut)ATM, wild-type TP53, mutTP53, and an unidentified gene in radioresistant glioma cells. The LDR and HDR radiosensitivity correlates at lower doses (∼2 Gy HDR, ∼6 Gy LDR), but not at higher doses (HDR > 4 Gy; LDR > 6 Gy). The rate of LDR-induced loss of clonogenic survival changes at approximately 24 hours; wild-type TP53 cells become more resistant and mutTP53 cells become more sensitive. Redistribution induced by LDR irradiation also changes at approximately 24 hours. Conclusions: Radiosensitivity of human tumor cells to both LDR and HDR irradiation is genotype dependent. Analysis of coefficients that describe cellular radiosensitivity segregates 27 cell lines into four statistically distinct groups, each associating with specific genotypes. Changes in cellular radiosensitivity and redistribution in the cell cycle are strongly time dependent. Our data establish a genotype-dependent time-dependent model that predicts clonogenic survival, explains the inverse dose-rate effect, and suggests possible clinical applications

Effect of bifidobacteria implantation on the survival time of whole-body irradiated mice

International Nuclear Information System (INIS)

Yokokura, Teruo; Onoue, Masaharu; Mutai, Masahiko

1980-01-01

Letahl dose (2 KR) of gamma-ray was irradiated on the whole bodies of mice. Survival time after irradiation was significantly longer in mice with administration of both Bifidobacterium breve YIT 4008 and transgalactosyl oligosaccharide than in mice with administration of either of the two or nothing. (Tsunoda, M.)

The value of gated myocardial perfusion imaging for the evaluation of early treatment effectiveness of ischemic heart disease using Ad-HGF myocardial injection

International Nuclear Information System (INIS)

Feng Jianlin; Cheng Xu; Li Jianhua; Xu Zhaoqiang; Li Dianfu; Yuan Biao; Zhang Yourong; Cao Kejiang; Huang Jun

2008-01-01

Objective: Hepatocyte growth factor (HGF) has multipotent actions mediated by c- Mesenchymal epithelial transition factor (Met) receptor. Preclinical studies in animal models of myocardial ischemia demonstrated that treatment with HGF could benefit myocardial perfusion, cardiac remodeling, angiogenesis and myocardial function. This study used gated 99 Tc m -methoxyisobutylisonitrile (MIBI) myocardial perfusion imaging (G-MPI) to assess the early treatment effectiveness of adenovirus HGF (Ad-HGF) directly administered in ischemic heart disease (IHD) patients. Methods: Eighteen patients with IHD were divided into 3 groups receiving low dose [5 x 10 8 plaque forming unit (PFU)/site], medium (1.5 x 10 9 PFU/site) and high dose (5 x l0 9 PFU/site) of Ad-HGF. And the Ad-HGF was injected at 10 sites in each patient. Rest G-MPI was performed before and after treatment for myocardial perfusion and left ventricular function measurement. Stata 7.0 was used to analyse the data. Results: (1) After Ad-HGF, myocardial perfusion was improved in 3/6, 5/6 and 6/6 patients in low, medium and high dosage groups. The dosage of AD-HGF was closely correlated with the improvement of myocardial perfusion (χ 2 =4.34, P<0.05). (2) Left ventricular ejection fraction (LVEF) was significantly increased [(50.1 ± 6.4)% vs (58.7 ± 5.6)%, t=6.1, P<0.01], end-diastolic volume [EDV, (137.7 ± 33.2) ml vs (123.7 ± 32.7) ml] and end-systolic volume [ESV, (70.2 ± 22.4) ml vs (51.9 ± 14.9) ml] were significantly reduced. (3) The LVEFs were increased in all groups, and the LVEF improvement in the high dosage group [(8.6 ± 5.9)%] was significantly greater than the other two groups [(4.3 ± l.2)%, (6.8 ± 5.7)%]. The difference of post-treatment improvement on LVEF between the low and medium dosage groups was not significant. The dosage of Ad-HGF was closely correlated with the improvement of LVEF (r=0.67, P< 0.01). Conclusion: G-MPI is a reliable method for evaluating the early effectiveness of

The survival effects of V79 cells irradiated with carbon ions in different let

International Nuclear Information System (INIS)

Wang Jufang; Zhou Guangming; He Jing; Li Wenjian; Li Qiang; Dang Bingrong; Li Xinglin; Weng Xiaoqiong; Xie Hongmei; Wei Zengquan; Gao Qingxiang

2001-01-01

The survival of cultured Chinese V79 hamster cells irradiated with carbon ions with different LETs were investigated. Irradiation was performed at the heavy Ion Research Facility in Lanzhou (HIRFL). Results were compared with those obtained from the experiments with γ rats and could be concluded as follows: The survival curves for carbon ions showed as straight lines and were fitted to the one-target one-hit model, but for γ rays the curves with shoulders were fitted to the multi-target one-hit model. As the LETs were 125, 200 and 700 keV/μm for carbon ions, the inactivation cross section 35, 12 and 8 μm 2 , respectively, which suggested that under the experimental conditions, the lower the LET of carbon ions, the more seriously the irradiation killed cells. In the case of 125 keV/μm, the RBEs of carbon ions at the 0.1 and 0.37 survival levels were 1.47 and 2.19 respectively

Survival frequency and spectrum of induced mutations in Penicillium vermiculatum dangeard following

International Nuclear Information System (INIS)

Mitra, Jharna; Chaudhari, K.L.

1974-01-01

A comparative study on the sensitivity of UV, X-rays and gamma rays on conidia of Penicillium vermiculatum has been done. LD50 with UV-rays was shown with less than 60 second treatment at a dose of 6 x 10 3 ergs/mm 2 . Beyond 240 second treatment i.e. 2.4 x 10 4 ergs/mm 2 the survival percent remained almost the same, indicating resistance of surviving spores to the action of UV radiation. With X-rays an increase in the germination percent of conidia was noticed at dosages of 5 and 10 Kr. Abrupt fall in the survival percent was observed with increasing dosage of X-rays. A wide range of biochemical morphological mutants was obtained with UV irradiation as compared to those with X-rays. Nicotinic acid requiring mutants occurred frequently with X-rays and methionine requiring ones with gamma-rays. Compact colonial mutants were induced freely with X-rays and violet pigment producing ones with gamma-rays. (author)

Ensemble of cell survival experiments after ion irradiation for validation of RBE models

Energy Technology Data Exchange (ETDEWEB)

Friedrich, Thomas; Scholz, Uwe; Scholz, Michael [GSI Helmholtzzentrum fuer Schwerionenforschung, Darmstadt (Germany); Durante, Marco [GSI Helmholtzzentrum fuer Schwerionenforschung, Darmstadt (Germany); Institut fuer Festkoerperphysik, TU Darmstadt, Darmstadt (Germany)

2012-07-01

There is persistent interest in understanding the systematics of the relative biological effectiveness (RBE). Models such as the Local Effect Model (LEM) or the Microdosimetric Kinetic Model have the goal to predict the RBE. For the validation of these models a collection of many in-vitro cell survival experiments is most appropriate. The set-up of an ensemble of in-vitro cell survival data comprising about 850 survival experiments after both ion and photon irradiation is reported. The survival curves have been taken out from publications. The experiments encompass survival curves obtained in different labs, using different ion species from protons to uranium, varying irradiation modalities (shaped or monoenergetic beam), various energies and linear energy transfers, and a whole variety of cell types (human or rodent; normal, mutagenic or tumor; radioresistant or -sensitive). Each cell survival curve has been parameterized by the linear-quadratic model. The photon parameters have been added to the data base to allow to calculate the experimental RBE to any survival level. We report on experimental trends found within the data ensemble. The data will serve as a testing ground for RBE models such as the LEM. Finally, a roadmap for further validation and first model results using the data base in combination with the LEM are presented.

Comparison of six different models describing survival of mammalian cells after irradiation

International Nuclear Information System (INIS)

Sontag, W.

1990-01-01

Six different cell-survival models have been compared. All models are based on the similar assumption that irradiated cells are able to exist in one of three states. S A is the state of a totally repaired cell, in state S C the cell contains lethal lesions and in state S b the cell contains potentially lethal lesions i.e. those which either can be repaired or converted into lethal lesions. The differences between the six models lie in the different mathematical relationships between the three states. To test the six models, six different sets of experimental data were used which describe cell survival at different repair times after irradiation with sparsely ionizing irradiation. In order to compare the models, a goodness-of-fit function was used. The differences between the six models were tested by use of the nonparametric Mann-Whitney two sample test. Based on the 95% confidence limit, this required separation into three groups. (orig.)

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

Directory of Open Access Journals (Sweden)

Juliann G. Kiang

2014-01-01

Full Text Available 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 to 60Co-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.

Myocardial perfusion imaging, coronary angiography and histological examination in experimental treatment of Ad-HGF for myocardial infarction

International Nuclear Information System (INIS)

Li Jianhua; Feng Jianlin; Cheng Xu; Li Dianfu; Zhang Youfu

2007-01-01

Objective: Gene therapy has drawn a great attention. A swine model of adenovirus hepatocyte growth factor(Ad-HGF) treated myocardial infarction(MI) was utilized, with the effect being assessed by rest myocardial perfusion imaging, coronary angiography and histological examination. Methods: Three groups of MI swine treated with Ad-HGF at low dose [n=5, Ad-HGF 10 8 plague forming unit (PFU)/ site], medium dose(n=5, 4 x 10 8 PFU/site), and high dose (n=5, 5 x 10 9 PFU/site), a control group treated with normal saline(NS, n=5) and a blank control group (n=5) underwent rest myocardial perfusion imaging and coronary angiography before and after treatment. The imaging results were analyzed along with histological findings in each group. Results: The state of myocardial perfusion and Rentrop scores remained unchanged in the blank control and NS groups after treatment. Whereas there was a significant improvement in the two variables in all three groups treated with Ad-HGF. The scores of left circumflex coronary artery (LCX) before and after treated were 7.8 ± 1.3 and 16.4 ± 1.1 (low-dose), 8.2 ± 1.6 and 17.6 ± 0.9 (medium-dose), 8.4 ± 1.5 and 19.0 ± 0.7 (high-dose), respectively. No significant differences were noted among the 3 groups. The number of vessels of NS group was markedly less than that of other groups. Conclusion: Myocardial perfusion imaging seems to be more accurate than coronary angiography and histological examination in evaluating the effects of Ad-HGF on myocardial infarction. (authors)

Modification of survival and hematopoiesis in mice by tocopherol injection following irradiation

International Nuclear Information System (INIS)

Bichay, T.J.E.; Roy, R.M.

1986-01-01

The LD 50/30 of CD-1-female mice increased from 6.6 Gy to 7.0 Gy when 2.5 mg of dl-α-tocopherol was injected immediately post irradiation. Increased survival was associated with increased numbers of hematopoietic colony forming units (CFU). Endogeneous spleen colonies were found in greater numbers in the tocopherol-treated mice after irradiation. The vitamin, however, must be injected within five hours following irradiation to have this effect. The increased numbers of CFU in tocopherol-treated mice may be due to a stimulation of recovery of repair processes. Split-dose studies suggest that most repair of sublethal damage in hematopoietic stem cells take place within seven and nine hours following irradiation. Tocopherol injection appears to enhance the recovery manifested in the split-dose assay. There is also evidence that tocopherol-treatment caused an earlier onset of mitotic activity in CFU after irradiation. The increased number of spleen colonies in tocopherol-injected mice is not due to an altered CFU seeding efficiency associated with an altered spleen microenvironment. Tocopherol injection did not affect the shoulder of the stem cell survival curve using exogenous spleen colony assays of bone marrow-derived or spleen-derived hematopoietic stem cells. There appears to be a decrease in D 0 in the higher dose region (4.3 Gy) of the bone marrow exogenous SCA survival curves for the vehicle-injected and the non-injected groups; however, the tocopherol-injected group showed no evidence of change in radiosensitivity up to the highest dose used (5.0 Gy). Data may be interpreted to suggest that the therapeutic effect of tocopherol may involve repair of hematopoietic stem cell damage in the higher dose range of bone marrow syndrome. (orig.) [de

The effects of 137Cs irradiation and MAP on the survival and growth of salmonella Spp in pork

International Nuclear Information System (INIS)

Gao Meixu

2000-01-01

The effects of 137 Cs irradiation (0 to 2 kGy) and MAP combination treatment on the survival and growth of Salmonella Spp are studied in sterile pork in the absence of competing microflora. A central composite response-surface design is used to test the response of the pathogen to the treatments in a single experiment. Predictive equations are developed from the analyses of variances of the resulting data. The results show that the survival of Salmonella is significant decrease with the increasing of irradiation dose, but there are no evident effects on the survival of salmonella due to the MAP. Five kinds of MAP do not show the difference on the growth of Salmonella. 50% CO 2 treatment shows the irradiation protection of Salmonella compared with air. The results indicate that the treatment combined irradiation with MAP is not more effective for controlling the survival and growth of Salmonella Spp

Free radicals induced archive paper by irradiation

International Nuclear Information System (INIS)

Cutrubinis, M.; Moise, I.V.; Negut, C.D.; Georgescu, R.; Suvaila, R.; Virgolici, M.; Manea, M.M.

2011-01-01

Complete text of publication follows. Irradiation of archive paper (document archives of institutions, companies etc. and library or museum collections of books and documents) can solve the problems related to the bio-deterioration and bio-contamination of paper and sometimes save valuable cultural heritage paper items. For valuable paper items care should be taken to the degradation induced instantly by the ionising radiation to the cellulosic support and also to the long term post-irradiation effects. The free radicals formed due to the irradiation treatment could contribute to instant degradation of paper. Part of them are also trapped for months and years after irradiation and they could be related to the post-irradiation effects in paper items. In this study, different sorts of cellulosic support samples (soft wood and hard wood cellulose, contemporary paper, paper from archives and from collections etc.) have been irradiated with dosis up to 100 kGy and the radiation induced free radicals have been measured by ESR spectrometry. The ESR signals have shown the type and quantity of radiation induced free radicals. Their study can be used for a realistic estimation of the degradative effect of the ionising radiation treatment of archive paper.

Combined administration of mesenchymal stem cells overexpressing IGF-1 and HGF enhances neovascularization but moderately improves cardiac regeneration in a porcine model.

Science.gov (United States)

Gómez-Mauricio, Guadalupe; Moscoso, Isabel; Martín-Cancho, María-Fernanda; Crisóstomo, Verónica; Prat-Vidal, Cristina; Báez-Díaz, Claudia; Sánchez-Margallo, Francisco M; Bernad, Antonio

2016-07-16

Insulin-like growth factor 1 (IGF-1) and hepatocyte growth factor (HGF) are among the most promising growth factors for promoting cardiorepair. Here, we evaluated the combination of cell- and gene-based therapy using mesenchymal stem cells (MSC) genetically modified to overexpress IGF-1 or HGF to treat acute myocardial infarction (AMI) in a porcine model. Pig MSC from adipose tissue (paMSC) were genetically modified for evaluation of different therapeutic strategies to improve AMI treatment. Three groups of infarcted Large White pigs were compared (I, control, non-transplanted; II, transplanted with paMSC-GFP (green fluorescent protein); III, transplanted with paMSC-IGF-1/HGF). Cardiac function was evaluated non-invasively using magnetic resonance imaging (MRI) for 1 month. After euthanasia and sampling of the animal, infarcted areas were studied by histology and immunohistochemistry. Intramyocardial transplant in a porcine infarct model demonstrated the safety of paMSC in short-term treatments. Treatment with paMSC-IGF-1/HGF (1:1) compared with the other groups showed a clear reduction in inflammation in some sections analyzed and promoted angiogenic processes in ischemic tissue. Although cardiac function parameters were not significantly improved, cell retention and IGF-1 overexpression was confirmed within the myocardium. The simultaneous administration of IGF-1- and HGF-overexpressing paMSC appears not to promote a synergistic effect or effective repair. The combined enhancement of neovascularization and fibrosis in paMSC-IGF-1/HGF-treated animals nonetheless suggests that sustained exposure to high IGF-1 + HGF levels promotes beneficial as well as deleterious effects that do not improve overall cardiac regeneration.

Mutation induced with ion beam irradiation in rose

Energy Technology Data Exchange (ETDEWEB)

Yamaguchi, H. E-mail: yhiroya@nias.affrc.go.jp; Nagatomi, S.; Morishita, T.; Degi, K.; Tanaka, A.; Shikazono, N.; Hase, Y

2003-05-01

The effects of mutation induction by ion beam irradiation on axillary buds in rose were investigated. Axillary buds were irradiated with carbon and helium ion beams, and the solid mutants emerged after irradiation by repeated cutting back. In helium ion irradiation, mutations were observed in plants derived from 9 buds among 56 irradiated buds in 'Orange Rosamini' and in plants derived from 10 buds among 61 irradiated buds in 'Red Minimo'. In carbon ion, mutations were observed in plants derived from 12 buds among 88 irradiated buds in 'Orange Rosamini'. Mutations were induced not only in higher doses but also in lower doses, with which physiological effect by irradiation was hardly observed. Irradiation with both ion beams induced mutants in the number of petals, in flower size, in flower shape and in flower color in each cultivar.

PHA665752, a small-molecule inhibitor of c-Met, inhibits hepatocyte growth factor-stimulated migration and proliferation of c-Met-positive neuroblastoma cells

International Nuclear Information System (INIS)

Crosswell, Hal E; Dasgupta, Anindya; Alvarado, Carlos S; Watt, Tanya; Christensen, James G; De, Pradip; Durden, Donald L; Findley, Harry W

2009-01-01

c-Met is a tyrosine kinase receptor for hepatocyte growth factor/scatter factor (HGF/SF), and both c-Met and its ligand are expressed in a variety of tissues. C-Met/HGF/SF signaling is essential for normal embryogenesis, organogenesis, and tissue regeneration. Abnormal c-Met/HGF/SF signaling has been demonstrated in different tumors and linked to aggressive and metastatic tumor phenotypes. In vitro and in vivo studies have demonstrated inhibition of c-Met/HGF/SF signaling by the small-molecule inhibitor PHA665752. This study investigated c-Met and HGF expression in two neuroblastoma (NBL) cell lines and tumor tissue from patients with NBL, as well as the effects of PHA665752 on growth and motility of NBL cell lines. The effect of the tumor suppressor protein PTEN on migration and proliferation of tumor cells treated with PHA665752 was also evaluated. Expression of c-Met and HGF in NBL cell lines SH-EP and SH-SY5Y and primary tumor tissue was assessed by immunohistochemistry and quantitative RT-PCR. The effect of PHA665752 on c-Met/HGF signaling involved in NBL cell proliferation and migration was evaluated in c-Met-positive cells and c-Met-transfected cells. The transwell chemotaxis assay and the MTT assay were used to measure migration and proliferation/cell-survival of tumor cells, respectively. The PPAR-γ agonist rosiglitazone was used to assess the effect of PTEN on PHA665752-induced inhibition of NBL cell proliferation/cell-survival and migration High c-Met expression was detected in SH-EP cells and primary tumors from patients with advanced-stage disease. C-Met/HGF signaling induced both migration and proliferation of SH-EP cells. Migration and proliferation/cell-survival were inhibited by PHA665752 in a dose-dependent manner. We also found that induced overexpression of PTEN following treatment with rosiglitazone significantly enhanced the inhibitory effect of PHA665752 on NBL-cell migration and proliferation. c-Met is highly expressed in most tumors from

Ion irradiation-induced swelling and hardening effect of Hastelloy N alloy

Energy Technology Data Exchange (ETDEWEB)

Zhang, S.J. [Key Laboratory of Artificial Micro-and Nano-structures of Ministry of Education, School of Physics and Technology, Wuhan University, Wuhan 430072 (China); Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 (China); Li, D.H.; Chen, H.C.; Lei, G.H.; Huang, H.F.; Zhang, W.; Wang, C.B. [Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 (China); Yan, L., E-mail: yanlong@sinap.ac.cn [Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 (China); Fu, D.J. [Key Laboratory of Artificial Micro-and Nano-structures of Ministry of Education, School of Physics and Technology, Wuhan University, Wuhan 430072 (China); Tang, M. [Los Alamos National Laboratory, Los Alamos, NM 87545 (United States)

2017-06-15

The volumetric swelling and hardening effect of irradiated Hastelloy N alloy were investigated in this paper. 7 MeV and 1 MeV Xe ions irradiations were performed at room temperature (RT) with irradiation dose ranging from 0.5 to 27 dpa. The volumetric swelling increases with increasing irradiation dose, and reaches up to 3.2% at 27 dpa. And the irradiation induced lattice expansion is also observed. The irradiation induced hardening initiates at low ion dose (≤1dpa) then saturates with higher ion dose. The irradiation induced volumetric swelling may be ascribed to excess atomic volume of defects. The irradiation induced hardening may be explained by the pinning effect where the defects can act as obstacles for the free movement of dislocation lines. And the evolution of the defects' size and number density could be responsible for the saturation of hardness. - Highlights: •Irradiation Swelling: The irradiation induced volumetric swelling increases with ion dose. •Irradiation Hardening: The irradiation hardening initiates below 1 dpa, then saturates with higher ion dose (1–10 dpa). •Irradiation Mechanism: The irradiation phenomena are ascribed to the microstructural evolution of the irradiation defects.

Efficacy of prophylactic irradiation in altering renal allograft survival

International Nuclear Information System (INIS)

Faber, R.; Johnson, H.K.; Braren, H.V.; Richie, R.E.

1974-01-01

Renal allograft rejection is a complex phenomenon involving both cell-mediated and humoral antibody responses. Most transplant programs have used a combination of therapeutic modalites to combat the immune system in an attempt to prolong both allograft and patient survival. Corticosteroids (methylprednisolone (Solu-Medrol) and prednisone and azathioprine (Imuran) are widely accepted as immunosuppressive drugs; however, both are non-specific and have the disadvantage of compromising the recipients' defense mechanisms. Nevertheless, these drugs have proved to be essential to the success of renal transplantation and they are routinely used while the efficacy of other modalities continues to be evaluated. We could find no reports of a prospective study to evaluate the efficacy of prophylactic irradiation in the complex therapeutic situation of renal transplantation with the only variable being the administration of local graft irradiation. The purpose of this study was to evaluate prophylactic graft irradiation for its effectiveness in preventing graft rejection in conjunction with Imuran and corticosteroids

Hepatocyte growth factor limits autoimmune neuroinflammation via glucocorticoid-induced leucine zipper expression in dendritic cells.

Science.gov (United States)

Benkhoucha, Mahdia; Molnarfi, Nicolas; Dunand-Sauthier, Isabelle; Merkler, Doron; Schneiter, Gregory; Bruscoli, Stefano; Riccardi, Carlo; Tabata, Yasuhiko; Funakoshi, Hiroshi; Nakamura, Toshikazu; Reith, Walter; Santiago-Raber, Marie-Laure; Lalive, Patrice H

2014-09-15

Autoimmune neuroinflammation, including multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE), a prototype for T cell-mediated autoimmunity, is believed to result from immune tolerance dysfunction leading to demyelination and substantial neurodegeneration. We previously showed that CNS-restricted expression of hepatocyte growth factor (HGF), a potent neuroprotective factor, reduced CNS inflammation and clinical deficits associated with EAE. In this study, we demonstrate that systemic HGF treatment ameliorates EAE through the development of tolerogenic dendritic cells (DCs) with high expression levels of glucocorticoid-induced leucine zipper (GILZ), a transcriptional repressor of gene expression and a key endogenous regulator of the inflammatory response. RNA interference-directed neutralization of GILZ expression by DCs suppressed the induction of tolerance caused by HGF. Finally, adoptive transfer of HGF-treated DCs from wild-type but not GILZ gene-deficient mice potently mediated functional recovery in recipient mice with established EAE through effective modulation of autoaggressive T cell responses. Altogether, these results show that by inducing GILZ in DCs, HGF reproduces the mechanism of immune regulation induced by potent immunomodulatory factors such as IL-10, TGF-β1, and glucocorticoids and therefore that HGF therapy may have potential in the treatment of autoimmune dysfunctions. Copyright © 2014 by The American Association of Immunologists, Inc.

SIRT1 interacts with and protects glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from nuclear translocation: Implications for cell survival after irradiation

International Nuclear Information System (INIS)

Joo, Hyun-Yoo; Woo, Seon Rang; Shen, Yan-Nan; Yun, Mi Yong; Shin, Hyun-Jin; Park, Eun-Ran; Kim, Su-Hyeon; Park, Jeong-Eun; Ju, Yeun-Jin; Hong, Sung Hee; Hwang, Sang-Gu; Cho, Myung-Haing; Kim, Joon; Lee, Kee-Ho

2012-01-01

Highlights: ► SIRT1 serves to retain GAPDH in the cytosol, preventing GAPDH nuclear translocation. ► When SIRT1 is depleted, GAPDH translocation occurs even in the absence of stress. ► Upon irradiation, SIRT1 interacts with GAPDH. ► SIRT1 prevents irradiation-induced nuclear translocation of GAPDH. ► SIRT1 presence rather than activity is essential for inhibiting GAPDH translocation. -- Abstract: Upon apoptotic stimulation, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a cytosolic enzyme normally active in glycolysis, translocates into the nucleus and activates an apoptotic cascade therein. In the present work, we show that SIRT1 prevents nuclear translocation of GAPDH via interaction with GAPDH. SIRT1 depletion triggered nuclear translocation of cytosolic GAPDH even in the absence of apoptotic stress. Such translocation was not, however, observed when SIRT1 enzymatic activity was inhibited, indicating that SIRT1 protein per se, rather than the deacetylase activity of the protein, is required to inhibit GAPDH translocation. Upon irradiation, SIRT1 prevented irradiation-induced nuclear translocation of GAPDH, accompanied by interaction of SIRT1 and GAPDH. Thus, SIRT1 functions to retain GAPDH in the cytosol, protecting the enzyme from nuclear translocation via interaction with these two proteins. This serves as a mechanism whereby SIRT1 regulates cell survival upon induction of apoptotic stress by means that include irradiation.

Irradiation creep due to SIPA-induced growth

International Nuclear Information System (INIS)

Woo, C.H.

1980-01-01

An additional contribution to irradiation creep resulting from the stress-induced preferred adsorption (SIPA) effect is described - SIPA-induced growth (SIG). The mechanism of SIG is discussed and an expression for its contribution to irradiation creep developed. It is shown that SIG is very significant in comparison with SIPA. Enhancement of creep by swelling may also occur. (U.K.)

A Reevaluation of X-Irradiation Induced Phocomelia and Proximodistal Limb Patterning

Science.gov (United States)

Galloway, Jenna L.; Delgado, Irene; Ros, Maria A.; Tabin, Clifford J.

2009-01-01

Phocomelia is a devastating, rare congenital limb malformation in which the long bones are shorter than normal, with the upper portion of the limb being most severely affected. In extreme cases, the hands or fingers are attached directly to the shoulder and the most proximal elements (those closest to the shoulder) are entirely missing. This disorder, previously known in both autosomal recessive and sporadic forms, showed a dramatic increase in incidence in the early 1960’s due to the tragic toxicological effects of the drug thalidomide, which had been prescribed as a mild sedative1, 2. This human birth defect is mimicked in developing chick limb buds exposed to X-irradiation3-5. Both X-irradiation5 and thalidomide-induced phocomelia5, 6 have been interpreted as patterning defects in the context of the Progress Zone Model, which states that a cell’s proximodistal (PD) identity is determined by the length of time spent in a distal limb region termed the “Progress Zone” 7. Indeed, studies of X-irradiation induced phocomelia have served as one of the two major experimental lines of evidence supporting the validity of the Progress Zone Model. Here, using a combination of molecular analysis and lineage tracing, we show that X-irradiation-induced phocomelia is fundamentally not a patterning defect, but rather results from a time-dependent loss of skeletal progenitors. As skeletal condensation proceeds from the shoulder to fingers (in a proximal to distal direction), the proximal elements are differentially affected in limb buds exposed to radiation at early stages. This conclusion changes the framework for considering the effect of thalidomide and other forms of phocomelia, suggesting the possibility that the etiology lies not in a defect in the patterning process, but rather in progenitor cell survival and differentiation. Moreover, molecular evidence that PD patterning is unaffected following X-irradiation does not support the predictions of the Progress Zone

Longevity of irradiated burros

International Nuclear Information System (INIS)

Lushbaugh, C.C.; Brown, D.G.; Frome, E.L.

1986-01-01

During the course of external radiation exposures of burros to establish a dose-response curve for acute mortality after total irradiation, some of the animals at the three lowest exposures to gamma photons survived. These groups of 10, 9, and 10 burros were exposed to 320, 425, and 545 R, respectively. There were 10 unirradiated controls. In 1953, 20 burros were exposed to 375 R (gamma) in 25-R/week increments without acute mortality and were added to the life-span study. In 1957, 33 burros were exposed to mixed neutron-gamma radiation from nuclear weapons, and 14 controls were added. The total number of irradiated burros in the study was increased to 88 by the addition of 6 animals irradiated with 180 rads of neutron and gamma radiation (4:1) in a Godiva-type reactor in 1959. In this experiment two acute deaths occurred which were not included in the analysis. In the first 4 years after the single gamma exposures, there were deaths from pancytopenia and thrombocytopenia, obviously related to radiation-induced bone-marrow damage. After that period, however, deaths were from common equine diseases; no death has resulted from a malignant neoplasm. Of the original 112 burros, 15 survive (10 irradiated and 5 controls). Survival curves determined for unirradiated and neutron-gamma- and gamma-irradiated burros showed significant differences. The mean survival times were: controls, 28 years; gamma irradiation only, 26 years; and neutron-gamma irradiation, 23 years. 3 refs., 4 figs., 1 tab

Correlation between cell survival and DNA single-strand break repair proficiency in the Chinese hamster ovary cell lines AA8 and EM9 irradiated with 365-nm ultraviolet-A radiation

Energy Technology Data Exchange (ETDEWEB)

Churchill, M.E.; Peak, J.G.; Peak, M.J. (Argonne National Lab., IL (USA))

1991-02-01

Cell survival parameters and the induction and repair of DNA single-strand breaks were measured in two Chinese hamster ovary cell lines after irradiation with monochromatic UVA radiation of wavelength 365 nm. The radiosensitive mutant cell line EM9 is known to repair ionizing-radiation-induced single-strand breaks (SSB) more slowly than the parent line AA8. EM9 was determined to be 1.7-fold more sensitive to killing by 365-nm radiation than AA8 at the 10% survival level, and EM9 had a smaller shoulder region on the survival curve ({alpha} = 1.76) than AA8 ({alpha} = 0.62). No significant differences were found between the cell lines in the initial yields of SSB induced either by {gamma}-radiation (as determined by alkaline sucrose gradient sedimentation) or by 365-nm UVA (as determined by alkaline elution). For measurement of initial SSB, cells were irradiated at 0.5{sup o}C to minimize DNA repair processes. Rejoining of 365-nm induced SSB was measured by irradiating cells at 0.5{sup o}C, allowing them to repair at 37{sup o}C in full culture medium, and then quantitating the remaining SSB by alkaline elution. The repair of these breaks followed biphasic kinetics in both cell lines. EM9 repaired the breaks more slowly (T{sub 1/2} values of 1.3 and 61.3 min) than did AA8 (T{sub 1/2} values of 0.9 and 53.3 min), and EM9 also left more breaks unrepaired 90 min after irradiation (24% vs 8% for AA8). Thus, the sensitivity of EM9 to 365-nm radiation correlated with its deficiency in repairing DNA lesions revealed as SSB in alkaline elution. These results suggest that DNA may be a critical target in 365-nm induced cellular lethality and that the ability of AA8 and EM9 cells to repair DNA strand breaks may be related to their ability to survive 365-nm radiation. (author).

Analysis of radicals induced in irradiated foods

International Nuclear Information System (INIS)

Kishida, Keigo; Kaimori, Yoshihiko; Kawamura, Shoei; Sakamoto, Yuhki; Nakamura, Hideo; Ukai, Mitsuko; Kikuchi, Masahiro; Shimoyama, Yuhei; Kobayashi, Yasuhiko

2012-01-01

By electron spin resonance (ESR) spectroscopy, we revealed free radicals in γ-ray irradiated foods; black pepper, green coffee bean and ginseng. We also analyzed the decay behavior of radiation induced free radicals during storage of irradiated foods. The ESR spectrum of experimental irradiated foods consists of a sextet signal centered at g=2.0 and a singlet signal at the same g-value position and a singlet signal at g=4.0. The singlet signal at g=2.0 is originated from organic free radicals and its peak intensity showed the dependence of γ-ray irradiation dose levels. The signal intensity was decreased during storage. Only after 3 hours of radiation treatment the peak intensity was decreased fast and after that the intensity was decreased slowly. The relaxation times, T 1 and T 2 , of radiation induced free radicals showed the variations before and after irradiation. During long time storage period it was shown that T 1 was increased and T 2 was decreased. By analysis of decay process using the simulation methods based on the theory of reaction speed, it is considered that at least two kinds of radicals were induced in irradiated foods during long time storage. (author)

The evolution of interaction between grain boundary and irradiation-induced point defects: Symmetric tilt GB in tungsten

Science.gov (United States)

Li, Hong; Qin, Yuan; Yang, Yingying; Yao, Man; Wang, Xudong; Xu, Haixuan; Phillpot, Simon R.

2018-03-01

Molecular dynamics method is used and scheme of calculational tests is designed. The atomic evolution view of the interaction between grain boundary (GB) and irradiation-induced point defects is given in six symmetric tilt GB structures of bcc tungsten with the energy of the primary knock-on atom (PKA) EPKA of 3 and 5 keV and the simulated temperature of 300 K. During the collision cascade with GB structure there are synergistic mechanisms to reduce the number of point defects: one is vacancies recombine with interstitials, and another is interstitials diffuse towards the GB with vacancies almost not move. The larger the ratio of the peak defect zone of the cascades overlaps with the GB region, the statistically relative smaller the number of surviving point defects in the grain interior (GI); and when the two almost do not overlap, vacancy-intensive area generally exists nearby GBs, and has a tendency to move toward GB with the increase of EPKA. In contrast, the distribution of interstitials is relatively uniform nearby GBs and is affected by the EPKA far less than the vacancy. The GB has a bias-absorption effect on the interstitials compared with vacancies. It shows that the number of surviving vacancies statistically has increasing trend with the increase of the distance between PKA and GB. While the number of surviving interstitials does not change much, and is less than the number of interstitials in the single crystal at the same conditions. The number of surviving vacancies in the GI is always larger than that of interstitials. The GB local extension after irradiation is observed for which the interstitials absorbed by the GB may be responsible. The designed scheme of calculational tests in the paper is completely applicable to the investigation of the interaction between other types of GBs and irradiation-induced point defects.

Electron irradiation-induced defects in {beta}-SiC

Energy Technology Data Exchange (ETDEWEB)

Oshima, Ryuichiro [Osaka Prefectural Univ., Sakai (Japan). Reseach Inst. for Advanced Science and Technology

1996-04-01

To add information of point defects in cubic crystal SiC, polycrystal {beta}-SiC on the market was used as sample and irradiated by neutron and electron. In situ observation of neutron and electron irradiation-induced defects in {beta}-SiC were carried out by ultra high-voltage electronic microscope (UHVEM) and ordinary electronic microscope. The obtained results show that the electron irradiation-induced secondary defects are micro defects less than 20 nm at about 1273K, the density of defects is from 2x10{sup 17} to 1x10{sup 18}/cc, the secondary defects may be hole type at high temperature and the preexistant defects control nuclear formation of irradiation-induced defects, effective sink. (S.Y.)

Irradiation-enhanced and-induced mass transport

International Nuclear Information System (INIS)

Rehn, L.E.

1989-01-01

Irradiation can be used to enhance diffusion, that is, to increase the rate at which equilibrium is attained, as well as to induce nonequilibrium changes. The main factors influencing whether irradiation will drive a material toward or away from equilibrium are the initial specimen microstructure and geometry, irradiation temperature, and primary recoil spectrum. This paper summarizes known effects of irradiation temperature and primary recoil spectrum on mass transport during irradiation. In comparison to either electron or heavy-ion irradiation, it is concluded that relatively low-energy, light-ion bombardment at intermediate temperatures offers the greatest potential to enhance the rate at which equilibrium is attained. The greatest departures from equilibrium can be expected from irradiation with similar particles at very low temperatures

Survival of human osteosarcoma cells and normal human fibroblasts following alpha particle irradiation

International Nuclear Information System (INIS)

Lloyd, E.L.; Gemmell, M.A.

1981-01-01

Cell survival of human osteosarcoma cells in culture following alpha particle irradiation is reported here for the first time. The osteosarcoma cell line (TE-85) is found to be less sensitive to inactivation by 5.6 MeV alpha particles (LET 86 keV/μm) than normal diploid human fibroblasts (NFS). Values for the mean lethal doses were estimated to be 103 rads for the TE-85 cells compared with 68 rads for the NFS cultures irradiated under identical conditions. It is postulated that the aneuploidy of the tumor cells with increased DNA chromosomal material may confer a selective advantage for the survival of tumor cells relative to normal cells with diploid chromosomes

Glioma cell death induced by irradiation or alkylating agent chemotherapy is independent of the intrinsic ceramide pathway.

Directory of Open Access Journals (Sweden)

Dorothee Gramatzki

Full Text Available Resistance to genotoxic therapy is a characteristic feature of glioma cells. Acid sphingomyelinase (ASM hydrolyzes sphingomyelin to ceramide and glucosylceramide synthase (GCS catalyzes ceramide metabolism. Increased ceramide levels have been suggested to enhance chemotherapy-induced death of cancer cells.Microarray and clinical data for ASM and GCS in astrocytomas WHO grade II-IV were acquired from the Rembrandt database. Moreover, the glioblastoma database of the Cancer Genome Atlas network (TCGA was used for survival data of glioblastoma patients. For in vitro studies, increases in ceramide levels were achieved either by ASM overexpression or by the GCS inhibitor DL-threo-1-phenyl-2-palmitoylamino-3-morpholino-1-propanol (PPMP in human glioma cell lines. Combinations of alkylating chemotherapy or irradiation and ASM overexpression, PPMP or exogenous ceramide were applied in parental cells. The anti-glioma effects were investigated by assessing proliferation, metabolic activity, viability and clonogenicity. Finally, viability and clonogenicity were assessed in temozolomide (TMZ-resistant cells upon treatment with PPMP, exogenous ceramide, alkylating chemotherapy, irradiation or their combinations.Interrogations from the Rembrandt and TCGA database showed a better survival of glioblastoma patients with low expression of ASM or GCS. ASM overexpression or PPMP treatment alone led to ceramide accumulation but did not enhance the anti-glioma activity of alkylating chemotherapy or irradiation. PPMP or exogenous ceramide induced acute cytotoxicity in glioblastoma cells. Combined treatments with chemotherapy or irradiation led to additive, but not synergistic effects. Finally, no synergy was found when TMZ-resistant cells were treated with exogenous ceramide or PPMP alone or in combination with TMZ or irradiation.Modulation of intrinsic glioma cell ceramide levels by ASM overexpression or GCS inhibition does not enhance the anti-glioma activity of

Epidermal growth factor receptor: an independent predictor of survival in astrocytic tumors given definitive irradiation

International Nuclear Information System (INIS)

An Zhu; Shaeffer, James; Leslie, Susan; Kolm, Paul; El-Mahdi, Anas M.

1996-01-01

Purpose: To determine whether the expression of epidermal growth factor receptor (EGFR) protein was predictive of patient survival independently of other prognostic factors in astrocytic tumors. Methods and Materials: Epidermal growth factor receptor protein expression was investigated immunohistochemically in formalin-fixed, paraffin-embedded surgical specimens of 55 glioblastoma multiforme, 14 anaplastic astrocytoma, and 2 astrocytomas given definitive irradiation. We evaluated the relationship of EGFR protein expression and tumor grade, histologic features, age at diagnosis, sex, patient survival, and recurrence-free survival. Results: The percentage of tumor cells which were EGFR positive related to reduced survival by Cox regression analysis in both univariate (p = 0.0424) and multivariate analysis (p = 0.0016). Epidermal growth factor receptor positivity was the only 1 of 11 clinical and histological variables associated with decreased recurrence-free survival by either univariate (p = 0.0353) or multivariate (p = 0.0182) analysis. Epidermal growth factor receptor protein expression was not related to patient age, sex, or histologic features. Conclusion: Epidermal growth factor receptor positivity was a significant and independent prognostic indicator for overall survival and recurrence-free survival for irradiated patients with astrocytic gliomas

Induced mitotic gynogenesis in common carp (Cyprinus carpio L.), optimizing irradiation dose of X- and gamma-ray

International Nuclear Information System (INIS)

Yousefian, M.; Amirinia, C.; Bercsenyi, M.; Horvath, L.

1997-01-01

Mitotic gynogenesis was induced in common carp, Cyprinus carpio L., in hatchery and laboratory conditions, using 60Co gamma-ray and X-ray for inactivation of sperm DNA and a subsequent heat shock for inducing endomitosis. The parameter examined was the dose of irradiation in the range of 70-140 Krad. Carp spermatozoa irradiated by 70-100 Krad doses showed higher motility and fertilization ability than the ones irradiated by 110-140 Krad. Sperm treated with doses of 70-90 Krad showed the same fertility rate, but lower survival rate at embryo stage compared with 100 Krad. The shock temperature and duration applied in these experiments for restoration of diploidy level were 40 degrees C plus/minus 0.1 and 2 min., respectively. The highest frequency of mitotic gynogenetic larvae was achieved by 100 Krad 60Co gamma ray at 34 min. after fertilization, - up to 12.2 percent (at 23 degrees C incubating temperature)

Carbon-ion beam irradiation kills X-ray-resistant p53-null cancer cells by inducing mitotic catastrophe.

Directory of Open Access Journals (Sweden)

Napapat Amornwichet

Full Text Available BACKGROUND AND PURPOSE: To understand the mechanisms involved in the strong killing effect of carbon-ion beam irradiation on cancer cells with TP53 tumor suppressor gene deficiencies. MATERIALS AND METHODS: DNA damage responses after carbon-ion beam or X-ray irradiation in isogenic HCT116 colorectal cancer cell lines with and without TP53 (p53+/+ and p53-/-, respectively were analyzed as follows: cell survival by clonogenic assay, cell death modes by morphologic observation of DAPI-stained nuclei, DNA double-strand breaks (DSBs by immunostaining of phosphorylated H2AX (γH2AX, and cell cycle by flow cytometry and immunostaining of Ser10-phosphorylated histone H3. RESULTS: The p53-/- cells were more resistant than the p53+/+ cells to X-ray irradiation, while the sensitivities of the p53+/+ and p53-/- cells to carbon-ion beam irradiation were comparable. X-ray and carbon-ion beam irradiations predominantly induced apoptosis of the p53+/+ cells but not the p53-/- cells. In the p53-/- cells, carbon-ion beam irradiation, but not X-ray irradiation, markedly induced mitotic catastrophe that was associated with premature mitotic entry with harboring long-retained DSBs at 24 h post-irradiation. CONCLUSIONS: Efficient induction of mitotic catastrophe in apoptosis-resistant p53-deficient cells implies a strong cancer cell-killing effect of carbon-ion beam irradiation that is independent of the p53 status, suggesting its biological advantage over X-ray treatment.

Effects of gamma ray and electron-beam irradiations on survival of anaerobic and facultatively anaerobic bacteria

International Nuclear Information System (INIS)

Miyahara, Michiko; Miyahara, Makoto

2002-01-01

An extension of the approval for food irradiation is desired due to the increase in the incidence of food poisoning in the world. One anaerobic (Clostridium perfringens) and four facultatively anaerobic (Bacillus cereus, Escherichia coli O157:H7, Listeria monocytogenes, and Salmonella Enteritidis) bacteria irradiated with gamma ray or electron beam (E-beam) were tested in terms of survival on agar under packaging atmosphere. Using pouch pack, effects of two irradiations on survival of anaerobic and facultatively anaerobic bacteria were evaluated comparatively. E-beam irradiation was more effective than gamma ray irradiation in decreasing the lethal dose 10% (D 10 ) value of B. cereus at 4 deg C, slightly more effective in that of E. coli O157, and similarly effective in that of the other three bacteria at 4 deg C. The gamma irradiation of the bacteria without incubation at 4 deg C before irradiation was more effective than that of the bacteria with incubation overnight at 4 deg C before irradiation in decreasing the D10 values of these bacteria (B. cereus, E. coli O157, and L. monocytogenes). Furthermore, ground beef patties inoculated with bacteria were irradiated with 1 kGy by E-beam (5 MeV) at 4 deg C. The inoculated bacteria in the 1-9 mm beef patties were killed by 1 kGy E-beam irradiation and some bacteria in more than 9 mm beef patties were not killed by the irradiation. (author)

Enhanced reactivation and mutagenesis of UV-irradiated adenovirus in normal human fibroblasts

International Nuclear Information System (INIS)

Bennett, C.B.; Rainbow, A.J.

1988-01-01

UV-enhanced reactivation (UVER) and UV-enhanced mutagenesis (UVEM) for two adenovirus temperature-sensitive mutants were examined following the infection of normal human fibroblasts. UV-irradiation of the virus alone resulted in dose-dependent increase in the UV-induced reversion frequency (RF) of viral progeny and a dose-dependent exponential decrease in progeny survival, when infecting non-irradiated cells. Analysis of the slopes of the UV-induced reversion curves suggested that 2.5 ± 0.3 and 2.4 ± 0.5 'hits' were required to produce a targeted reversion event among the viral progeny of Ad5ts36 and Ad5ts125 respectively. UV-irradiation of cells 24 h prior to infection resulted in a significant increase in progeny survival for UV-irradiated virus (UVER factor = 3.4 ± 0.8) concomitant with a significant increase in RF for UV-irradiated virus (targeted increase = 1.9 ± 0.3). The UV-induced RF per lethal hit to the virus was also significantly greater in UV-irradiated compared with non-irradiated cells. These results are consistent with the existence of a UV-inducible error-prone DNA repair mechanism in normal human cells. (author)

Survival and SOS response induction in ultraviolet B irradiated Escherichia coli cells with defective repair mechanisms.

Science.gov (United States)

Prada Medina, Cesar Augusto; Aristizabal Tessmer, Elke Tatjana; Quintero Ruiz, Nathalia; Serment-Guerrero, Jorge; Fuentes, Jorge Luis

2016-06-01

Purpose In this paper, the contribution of different genes involved in DNA repair for both survival and SOS induction in Escherichia coli mutants exposed to ultraviolet B radiation (UVB, [wavelength range 280-315 nm]) was evaluated. Materials and methods E. coli strains defective in uvrA, oxyR, recO, recN, recJ, exoX, recB, recD or xonA genes were used to determine cell survival. All strains also had the genetic sulA::lacZ fusion, which allowed for the quantification of SOS induction through the SOS Chromotest. Results Five gene products were particularly important for survival, as follows: UvrA > RecB > RecO > RecJ > XonA. Strains defective in uvrA and recJ genes showed elevated SOS induction compared with the wild type, which remained stable for up to 240 min after UVB-irradiation. In addition, E. coli strains carrying the recO or recN mutation showed no SOS induction. Conclusions The nucleotide excision and DNA recombination pathways were equally used to repair UVB-induced DNA damage in E. coli cells. The sulA gene was not turned off in strains defective in UvrA and RecJ. RecO protein was essential for processing DNA damage prior to SOS induction. In this study, the roles of DNA repair proteins and their contributions to the mechanisms that induce SOS genes in E. coli are proposed.

The HGF Receptor c-Met Is Overexpressed in Esophageal Adenocarcinoma

Directory of Open Access Journals (Sweden)

Luis J. Herrera

2005-01-01

Full Text Available The hepatocyte growth factor (HGF receptor, Met, has established oncogenic properties; however, its expression and function in esophageal adenocarcinoma (EA remain poorly understood. We aimed to determine the expression and potential alterations in Met expression in EA. Met expression was investigated in surgical specimens of EA, Barrett's esophagus (BE, and normal esophagus (NE using immunohistochemistry (IHC and quantitative reverse transcriptase polymerase chain reaction. Met expression, phosphorylation, and the effect of COX-2 inhibition on expression were examined in EA cell lines. IHC demonstrated intense Met immunoreactivity in all (100% EA and dysplastic BE specimens. In contrast, minimal immunostaining was observed in BE without dysplasia or NE specimens. Met mRNA and protein levels were increased in three EA cell lines, and Met protein was phosphorylated in the absence of serum. Sequence analysis found the kinase domain of c-met to be wild type in all three EA cell lines. HGF mRNA expression was identified in two EA cell lines. In COX-2-overexpressing cells, COX-2 inhibition decreased Met expression. Met is consistently overexpressed in EA surgical specimens and in three EA cell lines. Met dysregulation occurs early in Barrett's dysplasia to adenocarcinoma sequence. Future study of Met inhibition as a potential biologic therapy for EA is warranted.

Irradiation-induced amorphization process in graphite

Energy Technology Data Exchange (ETDEWEB)

Abe, Hiroaki [Japan Atomic Energy Research Inst., Takasaki, Gunma (Japan). Takasaki Radiation Chemistry Research Establishment

1996-04-01

Effects of the element process of irradiation damage on irradiation-induced amorphization processes of graphite was studied. High orientation thermal decomposed graphite was cut about 100 nm width and used as samples. The irradiation experiments are carried out under the conditions of electronic energy of 100-400 KeV, ion energy of 200-600 KeV, ionic species Xe, Ar, Ne, C and He and the irradiation temperature at from room temperature to 900 K. The critical dose ({phi}a) increases exponentially with increasing irradiation temperature. The displacement threshold energy of graphite on c-axis direction was 27 eV and {phi}a{sup e} = 0.5 dpa. dpa is the average number of displacement to atom. The critical dose of ion irradiation ({phi}a{sup i}) was 0.2 dpa at room temperature, and amorphous graphite was produced by less than half of dose of electronic irradiation. Amorphization of graphite depending upon temperature is discussed. (S.Y.)

Disinfestation of stored rice and corn grains by gamma irradiation. 3. Survival values for irradiated rice weevil and flour beetle and comparison of gamma irradiation and fumigation of weevil infested grains

International Nuclear Information System (INIS)

Manoto, E.C.; Villarcarlos, L.T.

1976-02-01

Survival values for Sitophilus oryzae and Tribolium castaneum adults were studied using gamma radiation dosage of 25, 50, 100 and 150 krad. Results with the two species seemed similar, although the rice weevil appeared the more sensitive. Rice and corn grains were artificially infested with Sitophilus oryzae and then treated with gamma radiation or fumigation. Both treatment reduced or eliminated adult emergence although fumigation left some insecticidal residues in corn. Sterility in the adult weevils was induced by 15 or 25 krad treatment of gamma radiation. A practical control level for bulk irradiation of rice or corn grains could probably be achieved by a 25 krad treatment although complete disinfestation should be achieved by a 50 krad treatment

Survival of Listeria monocytogenes in mozzarella cheese and ice cream exposed to gamma irradiation

International Nuclear Information System (INIS)

Hashisaka, A.E.; Weagant, S.D.; Dong, F.M.

1989-01-01

The survival of Listeria monocytogenes preinoculated into ice cream and mozzarella cheese prior to gamma-irradiation treatment was determined. Samples were maintained at -78 degrees C and exposed to targeted doses of 2, 4, 8, 16, and 32 kGy of gamma-irradiation. The calculated D10 values were 1.4 kGy for mozzarella cheese and 2.0 kGy for ice cream. The effective level of irradiation (12D) for inactivating L. monocytogenes was 16.8 kGy for mozzarella cheese and 24.4 kGy for ice cream

Effect of total lymphoid irradiation on pancreatic islet xenograft survival in rats

International Nuclear Information System (INIS)

Nakajima, Y.; Lie, T.S.; Nakauo, H.; Nakagawa, K.; Segawa, M.

1984-01-01

Before transplantation of Syrian hamster pancreatic islet xenografts to diabetic rats the recipients received total lymphatic system irradiation and cyclosporin A treatment after transplantation for immunosuppression. The xenograft survival times were measured and the rat anti-hamster lymphocytotoxic titers were determined by 51 Cr release assay

Effect of total lymphoid irradiation on pancreatic islet xenograft survival in rats

Energy Technology Data Exchange (ETDEWEB)

Nakajima, Y; Lie, T S [Bonn Univ. (Germany, F.R.). Chirurgische Klinik und Poliklinik; Nakauo, H; Nakagawa, K; Segawa, M [Nara Women' s Univ. (Japan). Dept. of Physics

1984-01-01

Before transplantation of Syrian hamster pancreatic islet xenografts to diabetic rats the recipients received total lymphatic system irradiation and cyclosporin A treatment after transplantation for immunosuppression. The xenograft survival times were measured and the rat anti-hamster lymphocytotoxic titers were determined by /sup 51/Cr release assay.

Genes involved in yeast survival after irradiation with fast neutrons

International Nuclear Information System (INIS)

Bozin, D.; Milosevic, M.J.

2001-01-01

Life on the Earth has evolved against a continuous background of ionizing radiation. It would be expected, therefore, that all possible mutations have been produced at some time or another; man-made radiation from medical or industrial sources will not result in any new types of mutation but will simply increase the whole spectrum of mutations that occur spontaneously. Any such lesion can be mutagenic and, in principle, lethal. To counteract the consequences of DNA damage, evolution has equipped all living cells with an intricate network of defense and repair systems. Together, these systems act as a kind of nuclear 'immune system' that is able to recognize and eliminate many types of DNA lesions. In the case of the yeast Saccharomyces cerevisiae, in these processes over 30 RAD genes participate. We tested the survival of haploid and diploid rad1 yeast mutant strains at a dose of 15 Gy of γ or fast neutron radiation. We demonstrated that the lethality of rad1 mutants both haploid and diploid are significantly higher after fast neutron irradiation. The results indicate to the role and position of these genes in the DNA repair of damages specifically induced by fast neutrons. (authors)

Evidence and analysis of radioresistance induced by protracted gamma irradiation of Chlorella pyrenoidosa chick, green unicellular alga

International Nuclear Information System (INIS)

Santier-Riviere, S.

1984-06-01

Chlorella cells, unicellular green algae, are a suitable living material to study radiosensitivity of eucaryotic cells after acute or protracted gamma irradiations. Cell survival and survival curves are taken as end-points. Methods of irradiation were defined taking in account interferences of the different factors which can intervene during the experimentation. Survival curves after protracted irradiation of Chlorella cell cultures in plateau-phase have a shape that can be explained by radioresistance. The population of surviving cells becomes radioresistant in front of protracted and acute irradiations, acute irradiation allowing us to analyze radioresistance. Radioresistance increases with the total dose of protracted irradiation. The decrease of radiosensitivity with aging of cells is not able to explain the phenomenon. It is not due to selection of radioresistance cells by protracted irradiation. All the cells get radioresistance. Radioresistance decreases with the time when protracted irradiation is suppressed. It is not found in offspring. It is not a mutation but perhaps the effect of a stimulation of repair processes, but not potentially lethal damage repair [fr

Effect of BCNU combined with total body irradiation or cyclophosphamide on survival of dogs after autologous marrow grafts

International Nuclear Information System (INIS)

Paterson, A.H.G.; English, D.

1979-01-01

Dogs were treated with either: (1) 750 rad total body irradiation; (2) BCNU 2 or 4 mg/kg IV 48 hours prior to 750 rad total body irradiation; or (3) BCNU 4 mg/kg IV plus cyclophosphamide 30 mg/kg IV. Results showed that of 11 dogs who received 750 rad total body irradiation and did not receive cryopreserved autologous bone marrow cells, none survived, compared to an 88% survival (31 of 35 dogs) after 750 rad total body irradiation if the dogs received stored autologous bone marrow cells. However, when the dogs were treated with BCNU 2 or 4 mg/kg prior to 750 rad total body irradiation the survival rate, despite infusion of autologous bone marrow cells, dropped to 25% (3 of 12 dogs) for BCNU 2 mg/kg, and 17% (2 of 12 dogs) for BCNU 4 mg/kg. This effect did not seem to be due to direct serum inhibition of hemopoietic cell proliferation since serum obtained at various intervals after BCNU administrations failed to inhibit CFU growth in vitro. The dogs died from hemorrhage and infection; at autopsy there was hemorrhagic pneumonitis and intestinal ulcerations with petechial hemorrhages, suggesting that the combination of BCNU and total body irradiation may have synergistic toxicity on the canine gastro-intestinal tract. When BCNU was combined with cyclophosphamide, reversal of marrow toxicity occurred in 54% (6 of 11 dogs) with stored autologous bone marrow cells compared to no survival (0 of 8 dogs) with stored autologous bone marrow cells. Thus while autologous bone marrow grafts are useful for reversal of marrow toxicity due to many therapeutic protocols, such grafts alone may not provide protection against toxicity due to the combination of high dosage BCNU and total body irradiation

Origins of ion irradiation-induced Ga nanoparticle motion on GaAs surfaces

International Nuclear Information System (INIS)

Kang, M.; Wu, J. H.; Chen, H. Y.; Thornton, K.; Goldman, R. S.; Sofferman, D. L.; Beskin, I.

2013-01-01

We have examined the origins of ion irradiation-induced nanoparticle (NP) motion. Focused-ion-beam irradiation of GaAs surfaces induces random walks of Ga NPs, which are biased in the direction opposite to that of ion beam scanning. Although the instantaneous NP velocities are constant, the NP drift velocities are dependent on the off-normal irradiation angle, likely due to a difference in surface non-stoichiometry induced by the irradiation angle dependence of the sputtering yield. It is hypothesized that the random walks are initiated by ion irradiation-induced thermal fluctuations, with biasing driven by anisotropic mass transport

Radio protective effects of calcium channel blockers (Deltiazem) on survival of Saccharomyces cerevisiae cells irradiated with different doses of gamma rays

Energy Technology Data Exchange (ETDEWEB)

Alya, G; Shamma, M; Sharabi, N [Atomic Energy Commission, Damascus (Syrian Arab Republic), Dept. of Molecular Biology and Biotechnology

2007-03-15

Investigations of radioprotective effects of Deltiazem (as one of the commonly used calcium channel blockers, which is used in the treatment of acute and chronic angina and spasmo angina, in addition to the treatment of different types of essential hypertension) has been carried on Saccharomyces Cerevisiae cells. Cells cultures of the most famous yeast Saccharomyces Cerevisiae (bakers yeast) were irradiated with different doses of gamma rays. Results revealed that the necessary dose of gamma rays that leads to 10% of survived cellular population (D10 value) was about 256 Gy. This irradiation dose was used then in all irradiation experiments on culture of S. Cerevisiae cells in which different concentrations of Deltiazem (55, 110, 165 mg/Kg medium) were added before and after irradiation in order to study the radio protective effect of Deltiazem. Results showed that Deltiazem enhances survival percentage of irradiated S. Cerevisiae cultures in a concentration dependent manner. This study confirmed our previous works, which had demonstrated that Deltiazem protects lethally and supralethally irradiated rats, and enhances survival of pre-irradiated Deltiazem treated animals.(author)

Radio protective effects of calcium channel blockers (Deltiazem) on survival of Saccharomyces cerevisiae cells irradiated with different doses of gamma rays

International Nuclear Information System (INIS)

Alya, G.; Shamma, M.; Sharabi, N.

2007-03-01

Investigations of radioprotective effects of Deltiazem (as one of the commonly used calcium channel blockers, which is used in the treatment of acute and chronic angina and spasmo angina, in addition to the treatment of different types of essential hypertension) has been carried on Saccharomyces Cerevisiae cells. Cells cultures of the most famous yeast Saccharomyces Cerevisiae (bakers yeast) were irradiated with different doses of gamma rays. Results revealed that the necessary dose of gamma rays that leads to 10% of survived cellular population (D10 value) was about 256 Gy. This irradiation dose was used then in all irradiation experiments on culture of S. Cerevisiae cells in which different concentrations of Deltiazem (55, 110, 165 mg/Kg medium) were added before and after irradiation in order to study the radio protective effect of Deltiazem. Results showed that Deltiazem enhances survival percentage of irradiated S. Cerevisiae cultures in a concentration dependent manner. This study confirmed our previous works, which had demonstrated that Deltiazem protects lethally and supralethally irradiated rats, and enhances survival of pre-irradiated Deltiazem treated animals.(author)

Intra-myocardial injection of both growth factors and heart derived Sca-1+/CD31- cells attenuates post-MI LV remodeling more than does cell transplantation alone: neither intervention enhances functionally significant cardiomyocyte regeneration.

Directory of Open Access Journals (Sweden)

Xiaohong Wang

Full Text Available Insulin-like growth factor 1 (IGF-1 and hepatocyte growth factor (HGF are two potent cell survival and regenerative factors in response to myocardial injury (MI. We hypothesized that simultaneous delivery of IGF+HGF combined with Sca-1+/CD31- cells would improve the outcome of transplantation therapy in response to the altered hostile microenvironment post MI. One million adenovirus nuclear LacZ-labeled Sca-1+/CD31- cells were injected into the peri-infarction area after left anterior descending coronary artery (LAD ligation in mice. Recombinant mouse IGF-1+HGF was added to the cell suspension prior to the injection. The left ventricular (LV function was assessed by echocardiography 4 weeks after the transplantation. The cell engraftment, differentiation and cardiomyocyte regeneration were evaluated by histological analysis. Sca-1+/CD31- cells formed viable grafts and improved LV ejection fraction (EF (Control, 54.5+/-2.4; MI, 17.6+/-3.1; Cell, 28.2+/-4.2, n = 9, P<0.01. IGF+HGF significantly enhanced the benefits of cell transplantation as evidenced by increased EF (38.8+/-2.2; n = 9, P<0.01 and attenuated adverse structural remodeling. Furthermore, IGF+HGF supplementation increased the cell engraftment rate, promoted the transplanted cell survival, enhanced angiogenesis, and minimally stimulated endogenous cardiomyocyte regeneration in vivo. The in vitro experiments showed that IGF+HGF treatment stimulated Sca-1+/CD31- cell proliferation and inhibited serum free medium induced apoptosis. Supperarray profiling of Sca-1+/CD31- cells revealed that Sca-1+/CD31- cells highly expressed various trophic factor mRNAs and IGF+HGF treatment altered the mRNAs expression patterns of these cells. These data indicate that IGF-1+HGF could serve as an adjuvant to cell transplantation for myocardial repair by stimulating donor cell and endogenous cardiac stem cell survival, regeneration and promoting angiogenesis.

MeV single-ion beam irradiation of mammalian cells using the Surrey vertical nanobeam, compared with broad proton beam and X-ray irradiations

Energy Technology Data Exchange (ETDEWEB)

Prakrajang, K. [Plasma and Beam Physics Research Facility, Department of Physics and Materials Science, Faculty of Science, Chiang Mai University, Chiang Mai 50200 (Thailand); Faculty of Science, Maejo University, Chiang Mai 50290 (Thailand); Jeynes, J.C.G.; Merchant, M.J.; Kirkby, K.; Kirkby, N. [Surrey Ion Beam Center, Faculty of Engineering and Physical Science, University of Surrey, Guildford Surrey, GU2 7XH (United Kingdom); Thopan, P. [Plasma and Beam Physics Research Facility, Department of Physics and Materials Science, Faculty of Science, Chiang Mai University, Chiang Mai 50200 (Thailand); Yu, L.D., E-mail: yuld@fnrf.science.cmu.ac.th [Plasma and Beam Physics Research Facility, Department of Physics and Materials Science, Faculty of Science, Chiang Mai University, Chiang Mai 50200 (Thailand); Thailand Center of Excellence in Physics, Commission on Higher Education, 328 Si Ayutthaya Road, Bangkok 10400 (Thailand)

2013-07-15

Highlights: •Recently completed nanobeam at the Surrey Ion Beam Centre was used. •3.8-MeV single and broad proton beams irradiated Chinese hamster cells. •Cell survival curves were measured and compared with 300-kV X-ray irradiation. •Single ion irradiation had a lower survival part at ultra-low dose. •It implies hypersensitivity, bystander effect and cell cycle phase of cell death. -- Abstract: As a part of a systematic study on mechanisms involved in physical cancer therapies, this work investigated response of mammalian cells to ultra-low-dose ion beam irradiation. The ion beam irradiation was performed using the recently completed nanobeam facility at the Surrey Ion Beam Centre. A scanning focused vertical ion nano-beam was applied to irradiate Chinese hamster V79 cells. The V79 cells were irradiated in two different beam modes, namely, focused single ion beam and defocused scanning broad ion beam of 3.8-MeV protons. The single ion beam was capable of irradiating a single cell with a precisely controlled number of the ions to extremely low doses. After irradiation and cell incubation, the number of surviving colonies as a function of the number of the irradiating ions was measured for the cell survival fraction curve. A lower survival for the single ion beam irradiation than that of the broad beam case implied the hypersensitivity and bystander effect. The ion-beam-induced cell survival curves were compared with that from 300-kV X-ray irradiation. Theoretical studies indicated that the cell death in single ion irradiation mainly occurred in the cell cycle phases of cell division and intervals between the cell division and the DNA replication. The success in the experiment demonstrated the Surrey vertical nanobeam successfully completed.

Sub-micron indent induced plastic deformation in copper and irradiated steel

International Nuclear Information System (INIS)

Robertson, Ch.

1998-09-01

In this work we aim to study the indent induced plastic deformation. For this purpose, we have developed a new approach, whereby the indentation curves provides the mechanical behaviour, while the deformation mechanisms are observed thanks to Transmission Electron Microscopy (TEM). In order to better understand how an indent induced dislocation microstructure forms, numerical modeling of the indentation process at the scale of discrete dislocations has been worked out as well. Validation of this modeling has been performed through direct comparison of the computed microstructures with TEM micrographs of actual indents in pure Cu [001]. Irradiation induced modifications of mechanical behaviour of ion irradiated 316L have been investigated, thanks to the mentioned approach. An important hardening effect was reported from indentation data (about 50%), on helium irradiated 316L steel. TEM observations of the damage zone clearly show that this behaviour is associated with the presence of He bubbles. TEM observations of the indent induced plastic zone also showed that the extent of the plastic zone is strongly correlated with hardness, that is to say: harder materials gets a smaller plastic zone. These results thus clearly established that the selected procedure can reveal any irradiation induced hardening in sub-micron thick ion irradiated layers. The behaviour of krypton irradiated 316L steel is somewhat more puzzling. In one hand indeed, a strong correlation between the defect cluster size and densities on the irradiation temperature is observed in the 350 deg C -600 deg C range, thanks to TEM observations of the damage zone. On the other hand, irradiation induced hardening reported from indentation data is relatively small (about 10%) and shows no dependence upon the irradiation temperature (within the mentioned range). In addition, it has been shown that the reported hardening vanishes following appropriate post-irradiation annealing, although most of the TEM

In situ transmission electron microscope studies of ion irradiation-induced and irradiation-enhanced phase changes

International Nuclear Information System (INIS)

Allen, C.W.

1992-01-01

Motivated at least initially by materials needs for nuclear reactor development, extensive irradiation effects studies employing transmission electron microscopes (TEM) have been performed for several decades, involving irradiation-induced and irradiation-enhanced microstructural changes, including phase transformations such as precipitation, dissolution, crystallization, amorphization, and order-disorder phenomena. From the introduction of commercial high voltage electron microscopes (HVEM) in the mid-1960s, studies of electron irradiation effects have constituted a major aspect of HVEM application in materials science. For irradiation effects studies two additional developments have had particularly significant impact; the development of TEM specimen holder sin which specimen temperature can be controlled in the range 10-2200 K and the interfacing of ion accelerators which allows in situ TEM studies of irradiation effects and the ion beam modification of materials within this broad temperature range. This paper treats several aspects of in situ studies of electron and ion beam-induced and enhanced phase changes and presents two case studies involving in situ experiments performed in an HVEM to illustrate the strategies of such an approach of the materials research of irradiation effects

An experimental study of the effect of total lymphoid irradiation on the survival of skin allografts

International Nuclear Information System (INIS)

Park, Charn Il; Han, Man Chung

1981-01-01

The study was undertaken to determine the effect of fractionated high-dose total lymphoid irradiation (TLI) on the survival of skin allograft despite major histocompatibility difference. Total lymphoid irradiation is a relatively safe form of radiotherapy, has been used extensively to treat lymphoid malignancies in humans with few side effects. A total of 90 rats, Sprague-Dawley rat as recipient and Wistar rat as donor, were used for the experiment, of which 10 rats were used to determine mixed lymphocyte response (MLR) for antigenic difference and skin allografts was performed in 30 rats given total lymphoid irradiation to assess the immunosuppressive effect of total lymphoid irradiation despite major histocompatibility difference. In addition, the peripheral white blood cell counts and the proportion of lymphocytes was studied in 10 rats given total lymphoid irradiation but no skin graft to determine the effects of bone marrow suppression. The results obtained are summarized as follows. 1. The optimum dose of total lymphoid irradiation was between 1800 rads to 2400 rads. 2. The survival of skin graft on rats given total lymphoid irradiation (23.2 ± 6.0 days) was prolonged about three folds as compared to unirradiated control (8.7 ± 1.3 days). 3. Total lymphoid irradiation resulted in a severe leukopenia with marked lymphopenia, but the count was normal by the end of 3rd week. 4. The study suggests that total lymphoid irradiation is a nonlethal procedure that could be used successfully in animals to transplant allograft across major histocompatibility barriers

An experimental study of the effect of total lymphoid irradiation on the survival of skin allografts

Energy Technology Data Exchange (ETDEWEB)

Park, Charn Il; Han, Man Chung [College of Medicine, Seoul National University, Seoul (Korea, Republic of)

1981-06-15

The study was undertaken to determine the effect of fractionated high-dose total lymphoid irradiation (TLI) on the survival of skin allograft despite major histocompatibility difference. Total lymphoid irradiation is a relatively safe form of radiotherapy, has been used extensively to treat lymphoid malignancies in humans with few side effects. A total of 90 rats, Sprague-Dawley rat as recipient and Wistar rat as donor, were used for the experiment, of which 10 rats were used to determine mixed lymphocyte response (MLR) for antigenic difference and skin allografts was performed in 30 rats given total lymphoid irradiation to assess the immunosuppressive effect of total lymphoid irradiation despite major histocompatibility difference. In addition, the peripheral white blood cell counts and the proportion of lymphocytes was studied in 10 rats given total lymphoid irradiation but no skin graft to determine the effects of bone marrow suppression. The results obtained are summarized as follows. 1. The optimum dose of total lymphoid irradiation was between 1800 rads to 2400 rads. 2. The survival of skin graft on rats given total lymphoid irradiation (23.2 {+-} 6.0 days) was prolonged about three folds as compared to unirradiated control (8.7 {+-} 1.3 days). 3. Total lymphoid irradiation resulted in a severe leukopenia with marked lymphopenia, but the count was normal by the end of 3rd week. 4. The study suggests that total lymphoid irradiation is a nonlethal procedure that could be used successfully in animals to transplant allograft across major histocompatibility barriers.

Nitric oxide-mediated bystander signal transduction induced by heavy-ion microbeam irradiation

Science.gov (United States)

Tomita, Masanori; Matsumoto, Hideki; Funayama, Tomoo; Yokota, Yuichiro; Otsuka, Kensuke; Maeda, Munetoshi; Kobayashi, Yasuhiko

2015-07-01

In general, a radiation-induced bystander response is known to be a cellular response induced in non-irradiated cells after receiving bystander signaling factors released from directly irradiated cells within a cell population. Bystander responses induced by high-linear energy transfer (LET) heavy ions at low fluence are an important health problem for astronauts in space. Bystander responses are mediated via physical cell-cell contact, such as gap-junction intercellular communication (GJIC) and/or diffusive factors released into the medium in cell culture conditions. Nitric oxide (NO) is a well-known major initiator/mediator of intercellular signaling within culture medium during bystander responses. In this study, we investigated the NO-mediated bystander signal transduction induced by high-LET argon (Ar)-ion microbeam irradiation of normal human fibroblasts. Foci formation by DNA double-strand break repair proteins was induced in non-irradiated cells, which were co-cultured with those irradiated by high-LET Ar-ion microbeams in the same culture plate. Foci formation was suppressed significantly by pretreatment with an NO scavenger. Furthermore, NO-mediated reproductive cell death was also induced in bystander cells. Phosphorylation of NF-κB and Akt were induced during NO-mediated bystander signaling in the irradiated and bystander cells. However, the activation of these proteins depended on the incubation time after irradiation. The accumulation of cyclooxygenase-2 (COX-2), a downstream target of NO and NF-κB, was observed in the bystander cells 6 h after irradiation but not in the directly irradiated cells. Our findings suggest that Akt- and NF-κB-dependent signaling pathways involving COX-2 play important roles in NO-mediated high-LET heavy-ion-induced bystander responses. In addition, COX-2 may be used as a molecular marker of high-LET heavy-ion-induced bystander cells to distinguish them from directly irradiated cells, although this may depend on the time

Light ion irradiation for unfavorable soft tissue sarcoma

International Nuclear Information System (INIS)

Linstadt, D.; Castro, J.R.; Phillips, T.L.; Petti, P.L.; Collier, J.M.; Daftari, I.; Schoethaler, R.; Rayner, A.

1990-09-01

Between 1978 and 1989, 32 patients with unfavorable soft tissue sarcoma underwent light ion (helium, neon) irradiation with curative intent at Lawrence Berkeley Laboratory. The tumors were located in the trunk in 22 patients and head and neck in 10. Macroscopic tumor was present in 22 at the time of irradiation. Two patients had tumors apparently induced by previous therapeutic irradiation. Follow-up times for surviving patients ranged from 4 to 121 months (median 27 months). The overall 3-year actuarial local control rate was 62%; the corresponding survival rate was 50%. The 3-year actuarial control rate for patients irradiated with macroscopic tumors was 48%, while none of the patients with microscopic disease developed local recurrence (100%). The corresponding 3-year actuarial survival rates were 40% (macroscopic) and 78% (microscopic). Patients with retroperitoneal sarcoma did notably well; the local control rate and survival rate were 64% and 62%, respectively. Complications were acceptable; there were no radiation related deaths, while two patients (6%) required operations to correct significant radiation-related injuries. These results appear promising compared to those achieved by low -LET irradiation, and suggest that this technique merits further investigation

Survival of spermatogonial stem cells in the rat after split dose irradiation during LH-RH analogue treatment

International Nuclear Information System (INIS)

Kroonenburgh, M.J.P.G. van; Daal, W.A.J. van; Beck, J.L.; Vemer, H.M.; Rolland, R.

1987-01-01

A rat model has been created in which a single injection of an LH-RH analogue depot preparation (Zoladex, ICI 118630) produced a temporary interruption of the pituitary-gonadal axis. This effect applied during irradiation was investigated as a possible mechanism to protect the testis from radiation damage. A local testicular irradiation dose of 6.0 Gy was given either as a single dose or as a fractionated (2 x 3.0 Gy) dose at different time intervals ranging from 8 to 72 h. Stem cell survival was measured 11 weeks after irradiation by means of the repopulation index and the number of haploid cells (spermatids) measured by flow cytometry. Serum gonadotrophins and testosterone concentrations were measured to evaluate hormonal recovery. No significant differences were observed between serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone and the duration of the fractionation interval. Stem cell survival was higher following fractionated irradiation in comparison with the single dose. For the 8 h interval an increase in recovery ratio was found, amounting to a factor of 5 of the single dose value. The fluctuating pattern of the recovery curves indicated changes in radiosensitivity of stem cells. The combination of hormonal inhibition of spermatogenesis and fractionated irradiation led to a decrease in the absolute numbers of stem cells. However, the stem cell recovery curves were identical to those seen without hormonal inhibition. It was concluded that hormonal pretreatment with Zoladex during split dose irradiation had no protective effect on stem cell survival. 37 refs.; 4 figs

Estimation of γ irradiation induced genetic damage by Ames test

International Nuclear Information System (INIS)

Hosoda, Eiko

1999-01-01

Mutation by 60 Co γ irradiation was studied in five different histidine-requiring auxotrophs of Salmonella typhimurium. The strains TA98 (sensitive to frameshift) and TA100 (sensitive to base-pair substitution) were irradiated (10-84 Gy and 45-317 Gy, respectively) and revertants were counted. TA98 exhibited radiation-induced revertants, 2.8 fold of spontaneous revertants, although no significant increase was detected in TA100. Then, three other frameshift-sensitive strains TA1537, TA1538 and TA94 were irradiated in a dose of 61-167 Gy. Only in TA94, revertants increased 3.5 fold. Since spontaneous revertants are known to be independent of cell density, a decrease of bacterial number by γ irradiation was confirmed not to affect the induced revertants by dilution test. Thus the standard Ames Salmonella assay identified γ irradiation was confirmed not to affect the induced revertants by dilution test. Thus the standard Ames Salmonella assay identified γ irradiation as a mutagenetic agent. The mutagenicity of dinitropyrene, a mutagen widely existing in food, and dismutagenicity of boiling water insoluble fraction of Hizikia fusiforme, edible marine alga, were tested on γ induced revertant formation in TA98 and TA94. Dinitropyrene synergistically increased γ induced revertants and Hizikia insoluble fraction reduced the synergistic effect of dinitropyrene dependently on the concentration. (author)

Developmental toxicity and oxidative stress induced by gamma irradiation in zebrafish embryos.

Science.gov (United States)

Hu, Miao; Hu, Nan; Ding, Dexin; Zhao, Weichao; Feng, Yongfu; Zhang, Hui; Li, Guangyue; Wang, Yongdong

2016-11-01

This study aimed to evaluate the biological effects of gamma irradiation on zebrafish embryos. Different doses of gamma rays (0.01, 0.05, 0.1, 0.5 and 1 Gy) were used to irradiate zebrafish embryos at three developmental stages (stage 1, 6 h post-fertilization (hpf); stage 2, 12 hpf; stage three, 24 hpf), respectively. The survival, malformation and hatching rates of the zebrafish embryos were measured at the morphological endpoint of 96 hpf. The activities of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx) and glutathione S-transferase (GST) were assayed. Morphology analysis showed that gamma irradiation inhibited hatching and induced developmental toxicity in a dose-dependent manner. Interestingly, after irradiation the malformation rate changed not only in a dose-dependent manner but also in a developmental stage-dependent manner, indicating that the zebrafish embryos at stage 1 were more sensitive to gamma rays than those at other stages. Biochemical analysis showed that gamma irradiation modulated the activities of antioxidant enzymes in a dose-dependent manner. A linear relationship was found between GPx activity and irradiation dose in 0.1-1 Gy group, and GPx was a suitable biomarker for gamma irradiation in the dose range from 0.1 to 1 Gy. Furthermore, the activities of SOD, CAT, GR and GPx of the zebrafish embryos at stage 3 were found to be much higher than those at other stages, indicating that the zebrafish embryos at stage 3 had a greater ability to protect against gamma rays than those at other stages, and thus the activities of antioxidant enzymes changed in a developmental stage-dependent manner.

Developmental toxicity and oxidative stress induced by gamma irradiation in zebrafish embryos

International Nuclear Information System (INIS)

Hu, Miao; Hu, Nan; Ding, Dexin; Zhao, Weichao; Feng, Yongfu; Zhang, Hui; Li, Guangyue; Wang, Yongdong

2016-01-01

This study aimed to evaluate the biological effects of gamma irradiation on zebrafish embryos. Different doses of gamma rays (0.01, 0.05, 0.1, 0.5 and 1 Gy) were used to irradiate zebrafish embryos at three developmental stages (stage 1, 6 h post-fertilization (hpf); stage 2, 12 hpf; stage three, 24 hpf), respectively. The survival, malformation and hatching rates of the zebrafish embryos were measured at the morphological endpoint of 96 hpf. The activities of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx) and glutathione S-transferase (GST) were assayed. Morphology analysis showed that gamma irradiation inhibited hatching and induced developmental toxicity in a dose-dependent manner. Interestingly, after irradiation the malformation rate changed not only in a dose-dependent manner but also in a developmental stage-dependent manner, indicating that the zebrafish embryos at stage 1 were more sensitive to gamma rays than those at other stages. Biochemical analysis showed that gamma irradiation modulated the activities of antioxidant enzymes in a dose-dependent manner. A linear relationship was found between GPx activity and irradiation dose in 0.1-1 Gy group, and GPx was a suitable biomarker for gamma irradiation in the dose range from 0.1 to 1 Gy. Furthermore, the activities of SOD, CAT, GR and GPx of the zebrafish embryos at stage 3 were found to be much higher than those at other stages, indicating that the zebrafish embryos at stage 3 had a greater ability to protect against gamma rays than those at other stages, and thus the activities of antioxidant enzymes changed in a developmental stage-dependent manner. (orig.)

Developmental toxicity and oxidative stress induced by gamma irradiation in zebrafish embryos

Energy Technology Data Exchange (ETDEWEB)

Hu, Miao; Hu, Nan; Ding, Dexin; Zhao, Weichao; Feng, Yongfu; Zhang, Hui; Li, Guangyue; Wang, Yongdong [University of South China, Key Discipline Laboratory for National Defense for Biotechnology in Uranium Mining and Hydrometallurgy, Hengyang, Hunan Province (China)

2016-11-15

This study aimed to evaluate the biological effects of gamma irradiation on zebrafish embryos. Different doses of gamma rays (0.01, 0.05, 0.1, 0.5 and 1 Gy) were used to irradiate zebrafish embryos at three developmental stages (stage 1, 6 h post-fertilization (hpf); stage 2, 12 hpf; stage three, 24 hpf), respectively. The survival, malformation and hatching rates of the zebrafish embryos were measured at the morphological endpoint of 96 hpf. The activities of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx) and glutathione S-transferase (GST) were assayed. Morphology analysis showed that gamma irradiation inhibited hatching and induced developmental toxicity in a dose-dependent manner. Interestingly, after irradiation the malformation rate changed not only in a dose-dependent manner but also in a developmental stage-dependent manner, indicating that the zebrafish embryos at stage 1 were more sensitive to gamma rays than those at other stages. Biochemical analysis showed that gamma irradiation modulated the activities of antioxidant enzymes in a dose-dependent manner. A linear relationship was found between GPx activity and irradiation dose in 0.1-1 Gy group, and GPx was a suitable biomarker for gamma irradiation in the dose range from 0.1 to 1 Gy. Furthermore, the activities of SOD, CAT, GR and GPx of the zebrafish embryos at stage 3 were found to be much higher than those at other stages, indicating that the zebrafish embryos at stage 3 had a greater ability to protect against gamma rays than those at other stages, and thus the activities of antioxidant enzymes changed in a developmental stage-dependent manner. (orig.)

Clinical significance of estimation of changes in serum SF, VEGF and HGF levels and after transfusion of red blood cells in patients with chronic nephritis

International Nuclear Information System (INIS)

Mu Peidong; He Haoming

2011-01-01

Objective: To observe the changes of serum SF, VEGF and HGF levels and after transfusion of red blood cells (RBC) in patients with chronic nephritis. Methods: Serum SF (with RIA) and serum VEGF, HGF (with ELISA) levels were measured in 30 patients with chronic nephritis both before and after a course of transfusion of RBC and 35 controls. Results: Before transfusion the serum SF levels in the patients were significantly lower than those in controls (P 0.05). Conclusion: Determination of serum SF, VEGF and HGF levels were clinically useful for the progress, prognosis and judgement of chronic nephritis. (authors)

Magic-factor 1, a partial agonist of Met, induces muscle hypertrophy by protecting myogenic progenitors from apoptosis.

Directory of Open Access Journals (Sweden)

Marco Cassano

2008-09-01

Full Text Available Hepatocyte Growth Factor (HGF is a pleiotropic cytokine of mesenchymal origin that mediates a characteristic array of biological activities including cell proliferation, survival, motility and morphogenesis. Its high affinity receptor, the tyrosine kinase Met, is expressed by a wide range of tissues and can be activated by either paracrine or autocrine stimulation. Adult myogenic precursor cells, the so called satellite cells, express both HGF and Met. Following muscle injury, autocrine HGF-Met stimulation plays a key role in promoting activation and early division of satellite cells, but is shut off in a second phase to allow myogenic differentiation. In culture, HGF stimulation promotes proliferation of muscle precursors thereby inhibiting their differentiation.Magic-Factor 1 (Met-Activating Genetically Improved Chimeric Factor-1 or Magic-F1 is an HGF-derived, engineered protein that contains two Met-binding domains repeated in tandem. It has a reduced affinity for Met and, in contrast to HGF it elicits activation of the AKT but not the ERK signaling pathway. As a result, Magic-F1 is not mitogenic but conserves the ability to promote cell survival. Here we show that Magic-F1 protects myogenic precursors against apoptosis, thus increasing their fusion ability and enhancing muscular differentiation. Electrotransfer of Magic-F1 gene into adult mice promoted muscular hypertrophy and decreased myocyte apoptosis. Magic-F1 transgenic mice displayed constitutive muscular hypertrophy, improved running performance and accelerated muscle regeneration following injury. Crossing of Magic-F1 transgenic mice with alpha-sarcoglycan knock-out mice -a mouse model of muscular dystrophy- or adenovirus-mediated Magic-F1 gene delivery resulted in amelioration of the dystrophic phenotype as measured by both anatomical/histological analysis and functional tests.Because of these features Magic-F1 represents a novel molecular tool to counteract muscle wasting in major

The effect of caffeine and adenine on radiation induced suppression of DNA synthesis, and cell survival

International Nuclear Information System (INIS)

Wilcoxson, L.T.; Griffiths, T.D.

1984-01-01

Exposure of cultured mammalian cells to ionizing radiation or UV light results in a transient decrease in the rate of DNA synthesis. This depression in synthetic rate may be attenuated or deferred via a post-irradiation treatment with caffeine or adenine. It has been suggested that this attenuation may increase the fixation of damage and, therefore, increase radiation sensitivity. However, it has been previously reported that, for V79 cells treated with caffeine or adenine, no correlation exists between the extent of depression and cell survival. The present investigation expands upon these findings by examining the effect of caffeine or adenine post-irradiation treatment on two cell lines with normal UV sensitivity, mouse 3T3 and CHO AA8 cells, and one UV sensitive cell line, CHO UV5 cells. Both caffeine and adenine have been found to reduce, or delay, the suppression in DNA synthesis in all three cell lines. Surprisingly, caffeine appeared to induced even the UV5 cells to recover DNA synthetic ability. The amount of reduction in suppression of DNA synthesis, however, varies between the different cell lines and no consistent relationship with cell survival has emerged

Effect of pepleomycin combined with irradiation on cultured Chinese hamster V79 cells

International Nuclear Information System (INIS)

Saito, Tsutomu

1983-01-01

The combined effect of pepleomycin (PEP), a bleomycin derivative, with irradiation was investigated on cultured Chinese hamster V79 cells. An additive effect was observed when PEP and irradiation were given simultaneously. A time interval between PEP (50μg/ml for one hour) and subsequent irradiation (10 Gy) increased the survival, and it became maximum when the time interval exceeded 2 hours. PEP-induced potentially lethal damage (PLD) was recovered when trysinization was delayed, and this recovery increased the survival. When PEP was given at a time interval after initial irradiation, the survival was decreased to below that following simultaneous treatment of the two modalities, and it became minimum when the time interval was 5 to 6 hours. Cells in ''G 2 -block'' induced by 10 Gy irradiation were partially synchronized, and cells in G 2 -M phase were more sensitive to PEP than those in S phase. It was considered that cells became more sensitive to PEP when they were irradiated 5 to 6 hours previously. However, cells recovery at any cell age when trypsinization was delayed. The benefit of a time interval between the two modalities was decreased by this recovery. (author)

Anomalous dose-response characteristics induced by caffeine in ultraviolet-irradiated V79-79 Chinese hamster cells

International Nuclear Information System (INIS)

Schroy, C.B.; Todd, P.

1979-01-01

Cultured Chinese hamster cell line V79-79 exhibited an increase in survival with increasing UV fluence after a sharp decrease when exposed to 2.5 mM caffeine for 44 h after far-UV irradiation resulting in an anomalous maximum in the survival curve. No survival maximum was evident when either 0 or 1 mM caffeine is administered under the same conditions. The UV survival curve for 2.5 mM caffeine crossed the corresponding 1 mM curve and apparently became asymptotic to the 0 mM curve as UV fluence was increased. Chinese hamster cell lines V79-753B (related to V79-79 by derivation from the same parental line) and M3-1F3 (unrelated) exhibited only potentiation of post-UV lethality by the same concentration of caffeine and had no caffeine-induced anomalies in their survival curves. Xanthine, used alone or in combination with caffeine, only potentiated a slight amount of lethality and appeared not to be a major causative factor of the anomaly. (author)

The effect of vitamin E on cellular survival after X irradiation of lymphoma cells

International Nuclear Information System (INIS)

Fonck, K.; Kronings, A.W.T.

1978-01-01

Asynchronous cultures of a lymphocytic mouse leukaemic cell line L5178Y were X-irradiated under oxic and hypoxic conditions. The survival curves had almost no shoulder when the cells were grown under normal conditions and then irradiated in the presence of vitamin E, whereas a clear shoulder appeared when the cells were grown and irradiated in a medium supplemented with vitamin E (100 μg/ml). There was no change in the final sensitivity to lethal events in the vitamin E enriched cells. The results suggest that the radioprotective effect of vitamin E depends on its incorporation into the cell membranes. (U.K.)

Effects of non-implantation factors on survival rate of microbe irradiated by low-energy N+

International Nuclear Information System (INIS)

Yang Tianyou; Chen Linhai; Qin Guangyong; Li Zongwei; Su Mingjie; Wang Yanping; Chang Shenghe; Huo Yuping; Li Zongyi

2006-01-01

The effects of non-implantation factors, such as drying, vacuum and the staying time of the E.coli LE392 culture, on survival rate of E.coli LE392 were studied when E.coli LE392 was irradiated by the low-energy N + . The results show that the survival rate of E.coli LE392 does not reduce steadily all the time but rapidly drops sometime during drying. The survival rate of E.coli LE392 declines sharply as the samples are placed in vacuum, then falls in distinctively with increasing of time. the tolerance of E.coli LE392 towards vacuum increasingly strengthens when the E.coli LE392 culture is placed at room temperature. Preparing the culture in batchs can ensure the consistency of the irradiated samples and avoid errors caused by the inconsistent samples. When the non-implantation factors are controlled, E.coli is implanted by 30 kev N + of 1 x 10 14 cm -2 and 3 x 10 15 cm -2 , respectively. And the results show no difference in the E.coli's survival rates between batchs at the same dose. (authors)

Induced chlorophyll variation in pineapple c v. 'queen' by gamma irradiation (60Cobalt)

International Nuclear Information System (INIS)

Valencia, Lolita DC.

2012-01-01

Irradiation using gamma rays ( 60 Cobalt) coupled with in vitro culture techniques was undertaken to induce variation or mutation in pineapple. Calli from crown meristem tips of pineapple cv 'Queen' [Ananas comosus (L.) Merr.] were initiated using Murashiege and Skoog's basal meduim supplemented with 10mg/liter 4-amino-3,5,6-trichloro-2-pyrodinecarboxylic acid (Picloram). High percentage of growth and shoot proliferation was observed in basal medium supplemented with 50 μM benzene adenine purine (BAP) and 10 μM gibberrelic acid (GA) after 8 weeks in vitro. Regenerants derived from shoots using different doses of gamma rays (0, 5, 10, 15, 20, 25 and 30 Gy) were evaluated under laboratory conditions. Of the different doses, 15 Gy produced the most variegation in young shoots (chlorophyll variants) maintained in vitro. The variants appeared to have yellow and green color combinations of the young leaves of pineapple 'Queen' variety. When transplanted inside the greenhouse, high percentage of plantlets survival was observed, ranging from 90-95%. Of the different irradiation doses, variegation in young leaves was observed at 15, 20, 25 and 30 Gy. Further assessment on the effect of irradiation is currently being unertaken under screen house conditions. The variants produced could serve a basis for selection of ornamental-type pineapple. In addition, protocols developed on the use of in vitro culture techniques could be utilized as a tool for induced mutation breeding in pineapple. (author)

Influence of a uvrD mutation on survival and repair of X-irradiated Escherichia coli K-12 cells

International Nuclear Information System (INIS)

Schueren, E. van der; Youngs, D.A.; Smith, K.C.

1977-01-01

The presence of a uvrD mutation increased the X-ray sensitivities of E.coli wild-type and polA strains, but had no effect on the sensitivities of recA and recB strains, and little effect on a lexA strain. Incubation of irradiated cells in medium containing 2,4-dinitrophenol or chloramphenicol decreased the survival of wild-type and uvrD cells, but had no effect on the survival of recA, recB and lexA strains. Alkaline sucrose gradient sedimentation studies indicated that the uvrD strain is deficient in the growth-medium-dependent (Type III) repair of DNA single-strand breaks. These results indicate that the uvrD mutation inhibits certain rec + lex + -dependent repair processes, including the growth-medium-dependent (Type III) repair of X-ray-induced DNA single-strand breaks, but does not inhibit other rec + lex + -dependent processes that are sensitive to 2,4-dinitrophenol and chloramphenicol. (author)

Influence of a uvrD mutation on survival and repair of x-irradiated Escherichia coli K-12 cells

Energy Technology Data Exchange (ETDEWEB)

van der Schueren, E; Youngs, D A; Smith, K C [Stanford Univ., Calif. (USA). Dept. of Radiology

1977-06-01

The presence of a uvrD mutation increased the x-ray sensitivities of E.coli wild-type and polA strains, but had no effect on the sensitivities of recA and recB strains, and little effect on a lexA strain. Incubation of irradiated cells in medium containing 2,4-dinitrophenol or chloramphenicol decreased the survival of wild-type and uvrD cells, but had no effect on the survival of recA, recB and lexA strains. Alkaline sucrose gradient sedimentation studies indicated that the uvrD strain is deficient in the growth-medium-dependent (Type III) repair of DNA single-strand breaks. These results indicate that the uvrD mutation inhibits certain rec/sup +/lex/sup +/-dependent repair processes, including the growth-medium-dependent (Type III) repair of x-ray-induced DNA single-strand breaks, but does not inhibit other rec/sup +/lex/sup +/-dependent processes that are sensitive to 2,4-dinitrophenol and chloramphenicol.

Cell survival and radiation induced chromosome aberrations. Pt. 2

International Nuclear Information System (INIS)

Bauchinger, M.; Schmid, E.; Braselmann, H.

1986-01-01

Human peripheral lymphocytes were irradiated in whole blood with 0.5-4.0 Gy of 220 kVp X-rays and the frequency of chromosome aberrations was determined in 1st or 2nd division metaphases discriminated by fluorescence plus giemsa staining. Using the empirical distributions of aberrations among cells, cell survival and transmission of aberrations were investigated. Considering both daughter cells, we found that 20% of fragments and 55% of dicentrics or ring chromosomes are lost during the 1st cell division; i.e. cell survival rate from 1st to 2nd generation is mainly influenced by anaphase bridging of these two-hit aberrations. Cell survival to 2nd mitosis was calculated considering this situation and compared with the survival derived from the fraction of M1 cells without unstable aberrations. The resulting shouldered survival curves showed significantly different slopes, indicating that cell reproductive death is overestimated in the latter approach. (orig.)

Influence of preirradiational and postirradiational heating of lyophilized Micrococcus radioproteolyticus cells on their survival

Energy Technology Data Exchange (ETDEWEB)

Ryznar, L; Drasil, V [Ceskoslovenska Akademie Ved, Brno. Biofysikalni Ustav

1981-12-10

The survival curve of Micrococcus radioproteolyticus following gamma irradiation of lyophilized cells is characterized by a broad shoulder reaching as far as the dose range 10 - 20 kGy (1 - 2 Mrad). The course of the curve indicates that under these conditions most of the changes induced by irradiation have the character of sublethal damage, which the cell can repair. The course of the survival curve does not change if the lyophilized cells are heated prior to irradiation for 2 h at 60 /sup 0/C. Certain changes do occur if the preirradiational temperature is 80 /sup 0/C. If the cells are exposed to increased temperature after irradiation even a temperature of 60 /sup 0/C brings about a marked decrease in survival. A temperature of 80 /sup 0/C after irradiation leads to extensive changes in the shape of survival curves, which are characterized by a narrowing or even disappearing of the shoulders. It can be concluded from the results obtained that an increased temperature modifies the capability of irradiated lyophilized cells to repair radiation damage.

Influence of preirradiational and postirradiational heating of lyophilized Micrococcus radioproteolyticus cells on their survival

International Nuclear Information System (INIS)

Ryznar, L.; Drasil, V.

1981-01-01

The survival curve of Micrococcus radioproteolyticus following gamma irradiation of lyophilized cells is characterized by a broad shoulder reaching as far as the dose range 10 - 20 kGy (1 - 2 Mrad). The course of the curve indicates that under these conditions most of the changes induced by irradiation have the character of sublethal damage, which the cell can repair. The course of the survival curve does not change if the lyophilized cells are heated prior to irradiation for 2 h at 60 0 C. Certain changes do occur if the preirradiational temperature is 80 0 C. If the cells are exposed to increased temperature after irradiation even a temperature of 60 0 C brings about a marked decrease in survival. A temperature of 80 0 C after irradiation leads to extensive changes in the shape of survival curves, which are characterized by a narrowing or even disappearing of the shoulders. It can be concluded from the results obtained that an increased temperature modifies the capability of irradiated lyophilized cells to repair radiation damage. (author)

Analysis of survival curves for Rhizopus, Mucor and Penicillia irradiated with gamma radiation

International Nuclear Information System (INIS)

Ishiguro, Etsuji; Danno, Akibumi; Miyazato, Mitsuru

1994-01-01

This study was aimed to understand the survival pattern of some microorganisms which were treated by γ-sterilization. Though most of the works were concentrated and reported with D 10 -values, it was presently found that the γ-irradiated survival curves showed sigmoid pattern and L-values were reached about half of the D 10 -value for each strains. It was further confirmed that if L-values were used for practical sterilization with D 10 -values, the estimation of sterilized levels would become more accurate. (author). 10 refs., 3 figs., 1 tab

Survival of dental implants in native and grafted bone in irradiated head and neck cancer patients: a retrospective analysis.

Science.gov (United States)

Buddula, Aravind; Assad, Daniel A; Salinas, Thomas J; Garces, Yolanda I

2011-01-01

To study the long-term survival of dental implants placed in native or grafted bone in irradiated bone in subjects who had received radiation for head and neck cancer. A retrospective chart review was conducted for all patients who received dental implants following radiation treatment for head and neck cancer between May 1, 1987 and July 1, 2008. Only patients irradiated with a radiation dose of 50 Gy or greater and those who received dental implants in the irradiated field after head and neck radiation were included in the study. The associations between implant survival and patient/implant characteristics were estimated by fitting univariate marginal Cox proportional hazards models. A total of 48 patients who had prior head and neck radiation had 271 dental implants placed during May 1987-July 2008. There was no statistically significant difference between implant failure in native and grafted bone (P=0.76). Survival of implants in grafted bone was 82.3% and 98.1% in maxilla and mandible, respectively, after 3 years. Survival of implants in native bone in maxilla and mandible was 79.8% and 100%, respectively, after 3 years. For implants placed in the native bone, there was a higher likelihood of failure in the maxilla compared to the mandible and there was also a tendency for implants placed in the posterior region to fail compared to those placed in the anterior region. There was no significant difference in survival when implants were placed in native or grafted bone in irradiated head and neck cancer patients. For implants placed in native bone, survival was significantly influenced by the location of the implant (maxilla or mandible, anterior or posterior).

Irradiation-induced tumours of the head and neck

Energy Technology Data Exchange (ETDEWEB)

Aanesen, J P; Olofsson, J [Linkoepings Hoegskola (Sweden)

1979-09-01

Though irradiation-induced tumours are uncommon, they represent a well defined entity. At this Hospital, 14 irradiation-induced head and neck tumours were encountered in 11 patients over a 10-year period. The irradiation had been given for tuberculous lymphadenitis in 6 of the patients, for lupus vulgaris in one, and thyrotoxicosis in another; the other 3 patients had received radiotherapy for malignant tumours. The interval between the treatment and the diagnosis of the tumour disease ranged from 9 to 48 years (mean 32). Three of the patients had multiple tumours. In view of the risk of cancer-albeit a small one-associated with radiological diagnosis and radiotherapy, these should be performed only on strict indications, expecially in young patients.

Zinc finger protein 598 inhibits cell survival by promoting UV-induced apoptosis.

Science.gov (United States)

Yang, Qiaohong; Gupta, Romi

2018-01-19

UV is one of the major causes of DNA damage induced apoptosis. However, cancer cells adopt alternative mechanisms to evade UV-induced apoptosis. To identify factors that protect cancer cells from UV-induced apoptosis, we performed a genome wide short-hairpin RNA (shRNA) screen, which identified Zinc finger protein 598 (ZNF598) as a key regulator of UV-induced apoptosis. Here, we show that UV irradiation transcriptionally upregulates ZNF598 expression. Additionally, ZNF598 knockdown in cancer cells inhibited UV-induced apoptosis. In our study, we observe that ELK1 mRNA level as well as phosphorylated ELK1 levels was up regulated upon UV irradiation, which was necessary for UV irradiation induced upregulation of ZNF598. Cells expressing ELK1 shRNA were also resistant to UV-induced apoptosis, and phenocopy ZNF598 knockdown. Upon further investigation, we found that ZNF598 knockdown inhibits UV-induced apoptotic gene expression, which matches with decrease in percentage of annexin V positive cell. Similarly, ectopic expression of ZNF598 promoted apoptotic gene expression and also increased annexin V positive cells. Collectively, these results demonstrate that ZNF598 is a UV irradiation regulated gene and its loss results in resistance to UV-induced apoptosis.

Chemical reactions induced by fast neutron irradiation

International Nuclear Information System (INIS)

Katsumura, Y.

1989-01-01

Here, several studies on fast neutron irradiation effects carried out at the reactor 'YAYOI' are presented. Some indicate a significant difference in the effect from those by γ-ray irradiation but others do not, and the difference changes from subject to subject which we observed. In general, chemical reactions induced by fast neutron irradiation expand in space and time, and there are many aspects. In the time region just after the deposition of neutron energy in the system, intermediates are formed densely and locally reflecting high LET of fast neutrons and, with time, successive reactions proceed parallel to dissipation of localized energy and to diffusion of the intermediates. Finally the reactions are completed in longer time region. If we pick up the effects which reserve the locality of the initial processes, a significant different effect between in fast neutron radiolysis and in γ-ray radiolysis would be derived. If we observe the products generated after dissipation and diffusion in longer time region, a clear difference would not be observed. Therefore, in order to understand the fast neutron irradiation effects, it is necessary to know the fundamental processes of the reactions induced by radiations. (author)

Delayed reproductive death as a dominant phenotype in cell clones surviving X-irradiation

International Nuclear Information System (INIS)

Chang, W.P.; Little, J.B.

1992-01-01

Residual damage manifested as reduced cloning efficiency was observed in many of the cloned progeny of Chinese hamster ovary (CHO) cells and human carcinoma SQ-20B cells surviving X-irradiation. This stable phenotype, which we have termed delayed reproductive death, persisted for >50 generations of cell replication post-irradiation. Clones showing this phenotype were aneuploid, and formed colonies with a high proportion of giant cells. By somatic cell hybridization of CHO clones, the delayed reproductive death phenotype was found to be a dominant trait; the cloning efficiency of hybrid clones was persistently depressed, as compared with that of control hybrid cells. These results suggest that delayed reproductive death represents a specific cellular response that may persist in some of the progeny of mammalian cells for long periods after X-irradiation. (author)

Influence of the combined administration of antibiotic-resistant bifidobacteria and the corresponding antibiotics on the survival of irradiated mice

International Nuclear Information System (INIS)

Korshunov, V.M.; Pinegin, B.V.; Ivanova, N.P.; Mal'tsev, V.N.

1982-01-01

Mice irradiated with a dose of 700 R were injected with a certain antibiotic (kanamycin, gentamycin, ampicillim and antibiotic resistant bifidobacteria) according to three different schemes. According to the first scheme antibiotic is in ected during the period from 1 to 7-th day, bifidobacteria-on 1, 6, 5, 7, 10, 15, 20 and 25-th day after irradiation, according to the second scheme antibiotic and bifidobacteria were injected from the fifth up to 0-th day after irradiation according to the 3-d scheme antibiotics and bifidobacteria were injected from the first up to 21-st day with 48 h interval. The largest increase in survival rate percent of irradiated animals was observed during combined injection of preparations according to the third scheme. The least medicinal effect was noted during injection of antibiotic and bifidobacteria aceording to the second scheme. Antibiotics and bifidobacteria injected separately increased survival rate of irradiated mice but at a lesser degree as compared with their combined use

Bystander effect-induced mutagenicity in HPRT locus of CHO cells following BNCT neutron irradiation: Characteristics of point mutations by sequence analysis

Energy Technology Data Exchange (ETDEWEB)

Kinashi, Yuko [Research Reactor Institute, Kyoto University, Kumatori-cho, Sennan-gun, Osaka (Japan)], E-mail: kinashi@rri.kyoto-u.ac.jp; Suzuki, Minoru; Masunaga, Shinichiro; Ono, Koji [Research Reactor Institute, Kyoto University, Kumatori-cho, Sennan-gun, Osaka (Japan)

2009-07-15

To investigate bystander mutagenic effects induced by alpha particles during boron neutron capture therapy (BNCT), we mixed cells that were electroporated with borocaptate sodium (BSH), which led to the accumulation of {sup 10}B inside the cells, with cells that did not contain the boron compound. BSH-containing cells were irradiated with {alpha} particles produced by the {sup 10}B(n,{alpha}){sup 7}Li reaction, whereas cells without boron were only affected by the {sup 1}H(n,{gamma}){sup 2}H and {sup 14}N(n,{rho}){sup 14}C reactions. The frequency of mutations induced in the hypoxanthine-guanine phosphoribosyltransferase (HPRT) locus was examined in Chinese hamster ovary (CHO) cells irradiated with neutrons (Kyoto University Research Reactor: 5 MW). Neutron irradiation of 1:1 mixtures of cells with and without BSH resulted in a survival fraction of 0.1, and the cells that did not contain BSH made up 99.4% of the surviving cell population. Using multiplex polymerase chain reactions (PCRs), molecular structural analysis indicated that most of the mutations induced by the bystander effect were point mutations and that the frequencies of total and partial deletions induced by the bystander effect were lower than those resulting from the {alpha} particles produced by the {sup 10}B(n,{alpha}){sup 7}Li reaction or the neutron beam from the {sup 1}H(n,{gamma}){sup 2}H and {sup 14}N(n,{rho}){sup 14}C reactions. The types of point mutations induced by the BNCT bystander effect were analyzed by cloning and sequencing methods. These mutations were comprised of 65.5% base substitutions, 27.5% deletions, and 7.0% insertions. Sequence analysis of base substitutions showed that transversions and transitions occurred in 64.7% and 35.3% of cases, respectively. G:C{yields}T:A transversion induced by 8-oxo-guanine in DNA occurred in 5.9% of base substitution mutants in the BNCT bystander group. The characteristic mutations seen in this group, induced by BNCT {alpha} particles

Irradiation spectrum and ionization-induced diffusion effects in ceramics

Energy Technology Data Exchange (ETDEWEB)

Zinkle, S.J. [Oak Ridge National Lab., TN (United States)

1997-08-01

There are two main components to the irradiation spectrum which need to be considered in radiation effects studies on nonmetals, namely the primary knock-on atom energy spectrum and ionizing radiation. The published low-temperature studies on Al{sub 2}O{sub 3} and MgO suggest that the defect production is nearly independent of the average primary knock-on atom energy, in sharp contrast to the situation for metals. On the other hand, ionizing radiation has been shown to exert a pronounced influence on the microstructural evolution of both semiconductors and insulators under certain conditions. Recent work on the microstructure of ion-irradiated ceramics is summarized, which provides evidence for significant ionization-induced diffusion. Polycrystalline samples of MgO, Al{sub 2}O{sub 3}, and MgAl{sub 2}O{sub 4} were irradiated with various ions ranging from 1 MeV H{sup +} to 4 MeV Zr{sup +} ions at temperatures between 25 and 650{degrees}C. Cross-section transmission electron microscopy was used to investigate the depth-dependent microstructural of the irradiated specimens. Dislocation loop nucleation was effectively suppressed in specimens irradiated with light ions, whereas the growth rate of dislocation loops was enhanced. The sensitivity to irradiation spectrum is attributed to ionization-induced diffusion. The interstitial migration energies in MgAl{sub 2}O{sub 4} and Al{sub 2}O{sub 3} are estimated to be {le}0.4 eV and {le}0.8 eV, respectively for irradiation conditions where ionization-induced diffusion effects are expected to be negligible.

Micronucleus formation compared to the survival rate of human melanoma cells after X-ray and neutron irradiation and hyperthermia

Energy Technology Data Exchange (ETDEWEB)

van Beuningen, D.; Streffer, C.; Bertholdt, G.

1981-09-01

After neutron and X-ray irradiation and combined X-ray irradiation and hyperthermia (3 hours, 42/sup 0/C), the survival rate of human melanoma cells was measured by means of the colony formation test and compared to the formation of micronuclei. Neutrons had a stronger effect on the formation of micronuclei than the combination of X-rays and hyperthermia. X-rays had the lowest effect. The dose effect curve showed a break at that dose level at which a reduction of cells was observed in the cultures. A good relation between survival rate and formation of micronuclei was found for the X-ray irradiation, but not for the neutron irradiation and the combined treatment. These observations are discussed. At least for X-rays, the micronucleus test has turned out to be a good screening method for the radiosensitivity of a biologic system.

Effects of oxygen during γ-irradiation of Micrococcus radiodurans

International Nuclear Information System (INIS)

Myers, D.K.; Johnson, L.D.

1977-01-01

A study has been made of the effects of oxygen on the yield of double strand breaks in the DNA of Micrococcus radiodurans, and of the relation of these effects to cell death. The o.e.r. values for cell survival were considerably smaller than those for the yield of double strand breaks, although they showed similar trends after irradiation in different media. The o.e.r. values for the inhibition of post-irradiation enzymatic repair were similar to those for cell survival. The o.e.r. for radiation-induced breaks in DNA therefore seems to depend on radiochemical reactions that are occurring during irradiation rather than on a preferential enzymatic repair of those strand breaks that are produced by anoxic irradiation. Cell survival depends less on the number of double strand breaks produced than on the ability of the cell to repair the double strand breaks. The maximum yield of double strand breaks after oxic γ-irradiation was approximately 1.7 breaks/krad/10 10 Daltons, corresponding to 1 break per 610 eV. (U.K.)

Effects of oxygen during. gamma. irradiation of Micrococcus radiodurans

Energy Technology Data Exchange (ETDEWEB)

Myers, D K; Johnson, L D [Atomic Energy of Canada Ltd., Chalk River, Ontario. Chalk River Nuclear Labs.

1977-09-01

A study has been made of the effects of oxygen on the yield of double strand breaks in the DNA of Micrococcus radiodurans, and of the relation of these effects to cell death. The OER values for cell survival were considerably smaller than those for the yield of double strand breaks, although they showed similar trends after irradiation in different media. The OER values for the inhibition of post-irradiation enzymatic repair were similar to those for cell survival. The OER for radiation-induced breaks in DNA therefore seems to depend on radiochemical reactions that are occurring during irradiation rather than on a preferential enzymatic repair of those strand breaks that are produced by anoxic irradiation. Cell survival depends less on the number of double strand breaks produced than on the ability of the cell to repair the double strand breaks. The maximum yield of double strand breaks after oxic ..gamma.. irradiation was approximately 1.7 breaks/krad/10/sup 10/Daltons, corresponding to 1 break per 610 eV.

Irradiation-induced stress relaxation of Eurofer97 steel

International Nuclear Information System (INIS)

Luzginova, N.V.; Jong, M.; Rensman, J.W.; Hegeman, J.B.J.; Laan, J.G. van der

2011-01-01

The irradiation-induced stress relaxation behavior of Eurofer97 at 300 deg. C up to 3.4 dpa and under pre-stress loads typical for the ITER applications is investigated. The bolt specimens are pre-loaded from 30% to 90% of the yield strength. To verify the results obtained with the pre-stressed bolts, bent strips were investigated as well. The strips are bent into a pre-defined radius in order to achieve similar pre-stress levels. The irradiation-induced stress relaxation is found to be independent of the pre-stress level. 10-12% of the stress relaxation in Eurofer97 may be reached after a dose of 0.1 dpa, and after an irradiation dose of 2.7 dpa 42-47% of the original pre-stress is retained.

Irradiation effects of ultraviolet rays on Leptospira cells. Loss of motility, survive ability, and damages of cell structures

Energy Technology Data Exchange (ETDEWEB)

Maeda, Hidezo (Yamaguchi Univ., Ube (Japan). School of Medicine)

1982-12-01

The irradiation effects of ultraviolets rays (UV) on leptospira cells were investigated. Four serovar strains of Genus Leptospira ; L. copenhageni, L. canicola, L. biflexa and L. illini were used. A sterilization lamp (Toshiba-GL-15) was lighted at intervals of 90mm on the sample fluid for several minutes. Loss of motility, survival growth and morphological damages were recognized under several conditions. The medium conditions were important, that is, the Korthof's medium was less effective than phosphate buffered saline (PBS). The irradiation time was also important, that is, L. canicola cells in PBS lost their motility and survive ability within 300sec. of irradiation, however, much more time, such as 1.200sec. was necessary in Korthof's medium. This phenomenon may be depended upon defensibility of albumin in the latter. Among the strains, L. biflexa cells showed the highest resistance in loss of motility and survive ability, and other three strains were inferior. The remarkable efects of cellular structures were also seen in the materials with 30 min. of irradiation, in both immediate time or after 24h incubation. The damages observed after 24th of irradiation were much more drastic than those of immediate time. No effect could be seen on the cells suspended in the Korthof's medium irradiated for 24h. Regarding morphological effect, there appeared relaxation of helical body, spherical body and semighost as the immediate changes. Structural damages were recognized as the collapse of cell body, such as scattering of capsule, release of axial flagella, loss or change of cytoplasmic density and break down of wall membrane complex. These phenomena were regarded as the indirect effects of UV-irradiation and autolysis in a post-mortem change.

Protective effects of the fermented milk Kefir on X-ray irradiation-induced intestinal damage in B6C3F1 mice

International Nuclear Information System (INIS)

Teruya, Kiichiro; Nakamichi, Noboru; Shirahata, Sanetaka; Myojin-Maekawa, Yuki; Shimamoto, Fumio; Watanabe, Hiromitsu; Tokumaru, Koichiro; Tokumaru, Sennosuke

2013-01-01

Gastrointestinal damage associated with radiation therapy is currently an inevitable outcome. The protective effect of Kefir was assessed for its usefulness against radiation-induced gastrointestinal damage. A Kefir supernatant was diluted by 2- or 10-fold and administered for 1 week prior to 8 Gray (Gy) X-ray irradiation at a dose rate of 2 Gy/min, with an additional 15d of administration post-irradiation. The survival rate of control mice with normal drinking water dropped to 70% on days 4 through 9 post-irradiation. On the other hand, 100% of mice in the 10- and 2-fold-diluted Kefir groups survived up to day 9 post-irradiation (p<0.05 and p<0.01, respectively). Examinations for crypt regeneration against 8, 10 and 12 Gy irradiation at a dose rate of 4 Gy/min revealed that the crypt number was significantly increased in the mice administered both diluted Kefir solutions (p<0.01 for each). Histological and immunohistochemical examinations revealed that the diluted Kefir solutions protected the crypts from radiation, and promoted crypt regeneration. In addition, lyophilized Kefir powder was found to significantly recover the testis weights (p<0.05), but had no effects on the body and spleen weights, after 8 Gy irradiation. These findings suggest that Kefir could be a promising candidate as a radiation-protective agent. (author)

Relation of intracellular cyclic AMP to the shape of mammalian cell survival curves

International Nuclear Information System (INIS)

Lehnert, S.

1975-01-01

Results of experiments with V79 cells growing in tissue culture indicate that the reproductive survival of cells following irradiation is influenced by the level of intracellular 3', 5'-cyclic adenosine monophosphate (cyclic AMP) at the time of irradiation. Cells containing high levels of cyclic AMP induced by treatments with drugs show a characteristic survival curve in which the extent of the shoulder is increased so that the survival after low doses is enhanced. The exponential slope or D 0 , however, is decreased so that at high doses the survival of cells containing high levels of cyclic AMP may be less than that of controls. Naturally occurring changes in radiosensitivity such as those observed as cells pass through the division cycle, may also be related to parallel changes in cyclic AMP concentration occurring during the cycle. Injection of mice with compounds producing elevated cyclic AMP prior to whole-body irradiation increases survival at seven days post-irradiation. The shape of the survival curve for intestinal stem cells in these mice differs from that of the control in having an increased extrapolation number; no change in D 0 is observed in this in vivo situation. (author)

Survival of dental implants in native and grafted bone in irradiated head and neck cancer patients: A retrospective analysis

Directory of Open Access Journals (Sweden)

Aravind Buddula

2011-01-01

Full Text Available Aim: To study the long-term survival of dental implants placed in native or grafted bone in irradiated bone in subjects who had received radiation for head and neck cancer. Materials and Methods: A retrospective chart review was conducted for all patients who received dental implants following radiation treatment for head and neck cancer between May 1, 1987 and July 1, 2008. Only patients irradiated with a radiation dose of 50 Gy or greater and those who received dental implants in the irradiated field after head and neck radiation were included in the study. The associations between implant survival and patient/implant characteristics were estimated by fitting univariate marginal Cox proportional hazards models. Results: A total of 48 patients who had prior head and neck radiation had 271 dental implants placed during May 1987-July 2008. There was no statistically significant difference between implant failure in native and grafted bone (P=0.76. Survival of implants in grafted bone was 82.3% and 98.1% in maxilla and mandible, respectively, after 3 years. Survival of implants in native bone in maxilla and mandible was 79.8% and 100%, respectively, after 3 years. For implants placed in the native bone, there was a higher likelihood of failure in the maxilla compared to the mandible and there was also a tendency for implants placed in the posterior region to fail compared to those placed in the anterior region. Conclusion: There was no significant difference in survival when implants were placed in native or grafted bone in irradiated head and neck cancer patients. For implants placed in native bone, survival was significantly influenced by the location of the implant (maxilla or mandible, anterior or posterior.

Survival of synchronized diploid yeast after ultraviolet irradiation

International Nuclear Information System (INIS)

Nunes, E.; Lorido, L.; Gelos, U.

1975-01-01

Synchronized populations of diploid yeast were exposed to uv light and their survival thereafter upon immediate plating (IP) and after liquid holding (LH) treatment in the presence and absence of caffeine was examined. These cells were found to be most resistant to uv light during early budding (G 2 period). The effect of LH is positive throughout the cell cycle and is dependent on the radiosensitivity of the cells upon IP. Caffeine-sensitive and caffeine-insensitive components of dark repair were demonstrated. The uv light responses of logarithmic growing and synchronized populations were compared with x-ray responses of the same strain analyzed under the same conditions in a previous work. The pattern of variation in sensitivity throughout the cell cycle and the ability to recover are qualitatively similar. The caffeine-insensitive component of repair has a similar efficiency in uv and x-irradiated G 1 cells, increasing in uv-irradiated cells after the beginning of the DNA synthetic period and during the G 2 period. The findings observed under IP conditions are consistent with a model already proposed which requires the repair efficiency to oscillate during the cell cycle. The results suggest that repair pathways for lethal uv damage may share some common steps with those for x-ray damage

Modelling irradiation-induced softening in BCC iron by crystal plasticity approach

International Nuclear Information System (INIS)

Xiao, Xiazi; Terentyev, Dmitry; Yu, Long; Song, Dingkun; Bakaev, A.; Duan, Huiling

2015-01-01

Crystal plasticity model (CPM) for BCC iron to account for radiation-induced strain softening is proposed. CPM is based on the plastically-driven and thermally-activated removal of dislocation loops. Atomistic simulations are applied to parameterize dislocation-defect interactions. Combining experimental microstructures, defect-hardening/absorption rules from atomistic simulations, and CPM fitted to properties of non-irradiated iron, the model achieves a good agreement with experimental data regarding radiation-induced strain softening and flow stress increase under neutron irradiation. - Highlights: • A stress- and thermal-activated defect absorption model is proposed for the dislocation-loop interaction. • A temperature-dependent plasticity theory is proposed for the irradiation-induced strain softening of irradiated BCC metals. • The numerical results of the model match with the corresponding experimental data.

Modelling irradiation-induced softening in BCC iron by crystal plasticity approach

Energy Technology Data Exchange (ETDEWEB)

Xiao, Xiazi [State Key Laboratory for Turbulence and Complex System, Department of Mechanics and Engineering Science, College of Engineering, Peking University, Beijing 100871 (China); CAPT, HEDPS and IFSA Collaborative Innovation Center of MoE, Peking University, Beijing 100871 (China); Terentyev, Dmitry, E-mail: dterenty@SCKCEN.BE [Structural Material Group, Institute of Nuclear Materials Science, SCK-CEN, Mol (Belgium); Yu, Long; Song, Dingkun [State Key Laboratory for Turbulence and Complex System, Department of Mechanics and Engineering Science, College of Engineering, Peking University, Beijing 100871 (China); Bakaev, A. [Structural Material Group, Institute of Nuclear Materials Science, SCK-CEN, Mol (Belgium); Duan, Huiling, E-mail: hlduan@pku.edu.cn [State Key Laboratory for Turbulence and Complex System, Department of Mechanics and Engineering Science, College of Engineering, Peking University, Beijing 100871 (China); CAPT, HEDPS and IFSA Collaborative Innovation Center of MoE, Peking University, Beijing 100871 (China)

2015-11-15

Crystal plasticity model (CPM) for BCC iron to account for radiation-induced strain softening is proposed. CPM is based on the plastically-driven and thermally-activated removal of dislocation loops. Atomistic simulations are applied to parameterize dislocation-defect interactions. Combining experimental microstructures, defect-hardening/absorption rules from atomistic simulations, and CPM fitted to properties of non-irradiated iron, the model achieves a good agreement with experimental data regarding radiation-induced strain softening and flow stress increase under neutron irradiation. - Highlights: • A stress- and thermal-activated defect absorption model is proposed for the dislocation-loop interaction. • A temperature-dependent plasticity theory is proposed for the irradiation-induced strain softening of irradiated BCC metals. • The numerical results of the model match with the corresponding experimental data.

Irradiation-induced precipitates in a neutron irradiated 304 stainless steel studied by three-dimensional atom probe

Energy Technology Data Exchange (ETDEWEB)

Toyama, T., E-mail: ttoyama@imr.tohoku.ac.jp [International Research Center for Nuclear Materials Science, Institute for Materials Research, Tohoku University, Narita-cho 2145-2, Oarai, Ibaraki 311-1313 (Japan); Nozawa, Y. [International Research Center for Nuclear Materials Science, Institute for Materials Research, Tohoku University, Narita-cho 2145-2, Oarai, Ibaraki 311-1313 (Japan); Van Renterghem, W. [SCK-CEN, Nuclear Materials Science Institute, Boeretang 200, 2400 Mol (Belgium); Matsukawa, Y.; Hatakeyama, M.; Nagai, Y. [International Research Center for Nuclear Materials Science, Institute for Materials Research, Tohoku University, Narita-cho 2145-2, Oarai, Ibaraki 311-1313 (Japan); Al Mazouzi, A. [EDF R and D, Avenue des Renardieres Ecuelles, 77818 Moret sur Loing Cedex (France); Van Dyck, S. [SCK-CEN, Nuclear Materials Science Institute, Boeretang 200, 2400 Mol (Belgium)

2011-11-15

Highlights: > Irradiation-induced precipitates in a 304 stainless steel were investigated by three-dimensional atom probe. > The precipitates were found to be {gamma}' precipitates (Ni{sub 3}Si). > Post-irradiation annealing was performed to discuss the contribution of the precipitates to irradiation-hardening. - Abstract: Irradiation-induced precipitates in a 304 stainless steel, neutron-irradiated to a dose of 24 dpa at 300 deg. C in the fuel wrapper plates of a commercial pressurized water reactor, were investigated by laser-assisted three-dimensional atom probe. A high number density of 4 x 10{sup 23} m{sup -3} of Ni-Si rich precipitates was observed, which is one order of magnitude higher than that of Frank loops. The average diameter was {approx}10 nm and the average chemical composition was 40% Ni, 14% Si, 11% Cr and 32% Fe in atomic percent. Over a range of Si concentrations, the ratio of Ni to Si was {approx}3, close to that of {gamma}' precipitate (Ni{sub 3}Si). In some precipitates, Mn enrichment inside the precipitate and P segregation at the interface were observed. Post-irradiation annealing was performed to discuss the contribution of the precipitates to irradiation-hardening.

Induced disease resistance of satsuma mandarings against penicillium digitatum by gamma irradiation

International Nuclear Information System (INIS)

Jeong, Rae Dong

2017-01-01

Gamma irradiation, which is a type of ionizing radiation, can be used as a fruit inducible factor. In the present study, the effects of gamma irradiation on the resistance of mandarin fruits against Penicillium digitatum, the causal agent of postharvest green mold disease, were investigated. Pretreatment of a low dose of gamma irradiation effectively reduced the disease incidence and lesion diameter of mandarin fruits inoculated with P. digatatum during storage for 14 d. Interestingly, exposed to 400 Gy of gamma irradiation significantly maintained firmness and stimulated the synthesis of defense-related enzymes, (e.g., β-1,3-glucanase, phenylalanine, peroxidase, and polyphenol oxidase) and pathogenesis-related (PR) genes (e.g., PR-1 and PR-2). Therefore, the gamma irradiation-induced resistance against P. digatatum involves both changes of phenolic compounds and the induction of expression of defense-related genes. In addition, scanning electron microscopy analysis revealed that induced disease resistance by gamma irradiation signifcantly inhibits the growth of P. digatatum in mandarin fruits. These results suggest that the exposure of gamma irradiation is a potential methods for inducing the disease resistance of fruit to postharvest fungal pathogens and for extending the postharvest life of mandarin fruit

Induced disease resistance of satsuma mandarings against penicillium digitatum by gamma irradiation

Energy Technology Data Exchange (ETDEWEB)

Jeong, Rae Dong [Dept. of Applied Biology, Institute of Environmentally Friendly Agriculture, Chonnam National University, Gwangju (Korea, Republic of)

2017-06-15

Gamma irradiation, which is a type of ionizing radiation, can be used as a fruit inducible factor. In the present study, the effects of gamma irradiation on the resistance of mandarin fruits against Penicillium digitatum, the causal agent of postharvest green mold disease, were investigated. Pretreatment of a low dose of gamma irradiation effectively reduced the disease incidence and lesion diameter of mandarin fruits inoculated with P. digatatum during storage for 14 d. Interestingly, exposed to 400 Gy of gamma irradiation significantly maintained firmness and stimulated the synthesis of defense-related enzymes, (e.g., β-1,3-glucanase, phenylalanine, peroxidase, and polyphenol oxidase) and pathogenesis-related (PR) genes (e.g., PR-1 and PR-2). Therefore, the gamma irradiation-induced resistance against P. digatatum involves both changes of phenolic compounds and the induction of expression of defense-related genes. In addition, scanning electron microscopy analysis revealed that induced disease resistance by gamma irradiation signifcantly inhibits the growth of P. digatatum in mandarin fruits. These results suggest that the exposure of gamma irradiation is a potential methods for inducing the disease resistance of fruit to postharvest fungal pathogens and for extending the postharvest life of mandarin fruit.

The effect of embryonal thymic calf extracts on neonatally thymectomized mice and on mice lethally irradiated with gamma rays

International Nuclear Information System (INIS)

Czaplicki, J.; Blonska, B.; Stec, L.

1981-01-01

The effect of embryonal thymic calf extracts (ETCE) on mice thymectomized at birth was investigated. ETCE was found to induce an increase in leukopenia and decrease in the level of serum gamma globulins; it also reduced survival time in mice. The effect of ETCE on lethally irradiated mice was also examined. Only long-term administration of ETCE prior to gamma irradiation at 750 rad prolonged the survival time of mice (40% permanent survival) as compared with irradiated controls; the leukocytes from mice retained mitotic capability. Neither long-term treatment with ETCE prior to irradiation at 1000 rad, nor short-term administration prior to 750 rad affected survival time. ETCE administered after irradiation of mice with 750 rad caused a rapid decrease in blood leukocytes and a significantly lowered survival time. (Auth.)

Induced Mutation in Yellow Lotus by Gamma Irradiation

International Nuclear Information System (INIS)

Puripunyavanich, Vichai; Boonsirichai, Kanokporn

2006-01-01

Rhizomes of American yellow lotus were irradiated at eht dosed of 0, 10, 20 and 30 Gy, 10 rhizomes per treatment. They were planted in nursery pots. Unirradiated rhizomes gave out new shoots within 3-4 days. The survival rates of the 10, 20 and 30 Gy irradiated rhizomes at one month after transplanted were 80%, 30% and 10%, respectively. The radiation dose that resulted in a 50% death rate (LD 5 0) was approximately 17 Gy. The surviving plant lets were transplanted and grown in pots as the Agricultural Occupation Promotion and Development Center in Chiangmai and Chiangrai for three years. Normally, American yellow lotus does not flower in Thailand. However, a mutant was found to bear flower in Thailand. The mutant flower appeared a little different from the wild-type flower. The tip of its petals was more rounded than the pointy wild-type tip. The mutant will be propagated for clonal production or for use as a par net in breeding crosses with Thai white and pink lotuses

The survival and repair of DNA single-strand breaks in gamma-irradiated Escherichia coli adapted to methyl methane sulfonate

International Nuclear Information System (INIS)

Zhestyanikov, V.D.; Savel'eva, G.E.

1992-01-01

The survival and repair of single-strand breaks of DNA in gamma-irradiated E.coli adapted to methyl methane sulfonate (MMS) (20 mkg/ml during 3 hours) have been investigated. It is shown that the survival of adapted bacteria of radioresistant strains B/r, H/r30, AB1157 and W3110 pol + increases with DMF (dose modification factor) ranging within 1.4-1.8 and in radiosensitive strains B s-1 , AB1157 recA13 and AB1157 lexA3 with DMF ranging within 1.3-1.4, and does not change in strains with mutation in poLA gene P3478 poLA1 and 016 res-3. The increase in radioresistance during the adaptation to MMS correlates with the acceleration of repair of gamma-ray-induced single-strand breaks in the radioresistant strains B/r and W3110 pol + and with the appearance of the ability to repair some part of DNA single-strand breaks in the mutant B s-1

Hepatic injury after whole-liver irradiation in the rat

International Nuclear Information System (INIS)

Geraci, J.P.; Jackson, K.L.; Mariano, M.S.; Leitch, J.M.

1985-01-01

Radiation-induced hepatic injury in rats, which is characterized by marked ascites accompanied by liver necrosis, fibrosis, and vein lesions, is described in this study. These adverse sequelae are produced within 30 days after irradiation if there is surgical removal of two-thirds of the liver immediately after whole-liver irradiation. The LD/sub 50/30/ day and median survival time after liver irradiation and two-thirds partial hepatectomy is 24 Gy and 17 days, respectively. Death is preceded by reduction in liver function as measured by [ 131 I]-labeled rose bengal clearance. Prior to death, liver sepsis and endotoxemia were detected in most irradiated, partially hepatectomized animals. Pretreatment of the animals with endotoxin and/or antibiotic decontamination of the GI tract resulted in increased survival time, but no irradiated, partially hepatectomized animal survived beyond 63 days. This suggests that sepsis and endotoxemia resulting from the bacteria in the intestine are the immediate cause of death after 30-Gy liver irradiation and partial hepatectomy. It is concluded that the hepatectomized rat model is an economical and scientifically manageable experimental system to study a form of radiation hepatitis that occurs in compromised human livers

Intra-myocardial injection of both growth factors and heart derived Sca-1+/CD31- cells attenuates post-MI LV remodeling more than does cell transplantation alone: neither intervention enhances functionally significant cardiomyocyte regeneration.

Science.gov (United States)

Wang, Xiaohong; Li, Qinglu; Hu, Qingsong; Suntharalingam, Piradeep; From, Arthur H L; Zhang, Jianyi

2014-01-01

Insulin-like growth factor 1 (IGF-1) and hepatocyte growth factor (HGF) are two potent cell survival and regenerative factors in response to myocardial injury (MI). We hypothesized that simultaneous delivery of IGF+HGF combined with Sca-1+/CD31- cells would improve the outcome of transplantation therapy in response to the altered hostile microenvironment post MI. One million adenovirus nuclear LacZ-labeled Sca-1+/CD31- cells were injected into the peri-infarction area after left anterior descending coronary artery (LAD) ligation in mice. Recombinant mouse IGF-1+HGF was added to the cell suspension prior to the injection. The left ventricular (LV) function was assessed by echocardiography 4 weeks after the transplantation. The cell engraftment, differentiation and cardiomyocyte regeneration were evaluated by histological analysis. Sca-1+/CD31- cells formed viable grafts and improved LV ejection fraction (EF) (Control, 54.5+/-2.4; MI, 17.6+/-3.1; Cell, 28.2+/-4.2, n = 9, Pcell transplantation as evidenced by increased EF (38.8+/-2.2; n = 9, Pcell engraftment rate, promoted the transplanted cell survival, enhanced angiogenesis, and minimally stimulated endogenous cardiomyocyte regeneration in vivo. The in vitro experiments showed that IGF+HGF treatment stimulated Sca-1+/CD31- cell proliferation and inhibited serum free medium induced apoptosis. Supperarray profiling of Sca-1+/CD31- cells revealed that Sca-1+/CD31- cells highly expressed various trophic factor mRNAs and IGF+HGF treatment altered the mRNAs expression patterns of these cells. These data indicate that IGF-1+HGF could serve as an adjuvant to cell transplantation for myocardial repair by stimulating donor cell and endogenous cardiac stem cell survival, regeneration and promoting angiogenesis.

Preliminary examination of induced radioactivity in pepper by 10 MeV electron irradiation

International Nuclear Information System (INIS)

Katayama, Tadashi; Furuta, Masakazu; Sibata, Setsuko; Ito, Norio; Mizohata, Akira; Matsunami, Tadao; Toratani, Hirokazu; Takeda, Atsuhiko.

1991-01-01

β-ray measurement was performed on 10 MeV electron-irradiated black pepper and white pepper with liquid scintillation counter in order to reconfirm the wholesomeness of irradiated foods and present unambiguous data to general consumers concerning about the induced radioactivity in the irradiated foods. In irradiated black pepper no radioactivity other than from natural source, un-irradiated one, was detected. But in irradiated white pepper, it was suggested that induced radioactivity might be detected if the detection method was more improved. (author)

Energy related germination and survival rates of water-imbibed Arabidopsis seeds irradiated with protons

International Nuclear Information System (INIS)

Qin, H.L.; Xue, J.M.; Lai, J.N.; Wang, J.Y.; Zhang, W.M.; Miao, Q.; Yan, S.; Zhao, W.J.; He, F.; Gu, H.Y.; Wang, Y.G.

2006-01-01

In order to investigate the influence of ion energy on the germination and survival rates, water-imbibed Arabidopsis seeds were irradiated with protons in atmosphere. The ion fluence used in this experiment was in the range of 4 x 10 9 -1 x 10 14 ions/cm 2 . The ion energy is from 1.1 MeV to 6.5 MeV. According to the structure of the seed and TRIM simulation, the ions with the energy of 6.5 MeV can irradiate the shoot apical meristem directly whereas the ions with the energy of 1.1 MeV cannot. The results showed that both the germination and survival rates decrease while increasing the ion fluence, and the fluence-respond curve for each energy has different character. Besides the shoot apical meristem (SAM), which is generally considered as the main radiobiological target, the existence of a secondary target around SAM is proposed in this paper

Energy related germination and survival rates of water-imbibed Arabidopsis seeds irradiated with protons

Energy Technology Data Exchange (ETDEWEB)

Qin, H.L. [Key Laboratory of Heavy Ion Physics, MOE, Peking University, Beijing 100871 (China); Xue, J.M. [Key Laboratory of Heavy Ion Physics, MOE, Peking University, Beijing 100871 (China); Lai, J.N. [Key Laboratory of Heavy Ion Physics, MOE, Peking University, Beijing 100871 (China); Wang, J.Y. [Key Laboratory of Heavy Ion Physics, MOE, Peking University, Beijing 100871 (China); Zhang, W.M. [Key Laboratory of Heavy Ion Physics, MOE, Peking University, Beijing 100871 (China); Miao, Q. [Key Laboratory of Heavy Ion Physics, MOE, Peking University, Beijing 100871 (China); Yan, S. [Key Laboratory of Heavy Ion Physics, MOE, Peking University, Beijing 100871 (China); Zhao, W.J. [Key Laboratory of Heavy Ion Physics, MOE, Peking University, Beijing 100871 (China); He, F. [School of Life Science, Peking University, Beijing 100871 (China); Gu, H.Y. [School of Life Science, Peking University, Beijing 100871 (China); Wang, Y.G. [Key Laboratory of Heavy Ion Physics, MOE, Peking University, Beijing 100871 (China)]. E-mail: ygwang@pku.edu.cn

2006-04-15

In order to investigate the influence of ion energy on the germination and survival rates, water-imbibed Arabidopsis seeds were irradiated with protons in atmosphere. The ion fluence used in this experiment was in the range of 4 x 10{sup 9}-1 x 10{sup 14} ions/cm{sup 2}. The ion energy is from 1.1 MeV to 6.5 MeV. According to the structure of the seed and TRIM simulation, the ions with the energy of 6.5 MeV can irradiate the shoot apical meristem directly whereas the ions with the energy of 1.1 MeV cannot. The results showed that both the germination and survival rates decrease while increasing the ion fluence, and the fluence-respond curve for each energy has different character. Besides the shoot apical meristem (SAM), which is generally considered as the main radiobiological target, the existence of a secondary target around SAM is proposed in this paper.

Stem cell factor enhances the survival of murine intestinal stem cells after photon irradiation

International Nuclear Information System (INIS)

Leigh, B.R.; Khan, W.; Hancock, S.L.

1995-01-01

Recombinant rat stem cell factor (SCF) has been shown to decrease lethality in mice exposed to total-body irradiation (TBI) in the lower range of lethality through radioprotection of hematopoietic stem cells and acceleration of bone marrow repopulation. This study evaluates the effect of SCF on the survival of the intestinal mucosal stem cell after TBI. This non-hematopoietic cell is clinically relevant. Gastrointestinal toxicity is common during and after abdominal and pelvic radiation therapy and limits the radiation dose in these regions. As observed with bone marrow, the administration of SCF to mice prior to TBI enhanced the survival of mouse duodenal crypt stem cells. The maximum enhancement of survival was seen when 100 μ/kg of SCF was given intraperitoneally 8 h before irradiation. This regimen increased the survival of duodenal crypt stem cells after 12.0 Gy TBI from 22.5 ± 0.7 per duodenal cross section for controls to 30.0 ± 1.7 after treatment with SCF (P=0.03). The TBI dose producing 50% mortality of 6 days (LD 50/6 ) was increased from 14.9 Gy for control mice to 19.0 Gy for mice treated with SCF (dose modification factor = 1.28). These findings demonstrate that SCF (dose modification factor = 1.28). These findings demonstrate that SCF has radioprotective effects on a non-hematopoietic stem cell population and suggest that SCF may be of clinical value in preventing radiation injury to the intestine. 29 refs., 4 figs

Effect of irradiation on the dental pulp tissues in streptozotocin-induced diabetic rats

International Nuclear Information System (INIS)

Kang, Ho Duk; Hwang, Eui Hwan; Lee, Sang Rae

2005-01-01

To observe the histological changes in the pulp tissues of mandibular molars in streptozotocin-induced diabetic rats after irradiation. The male Sprague-Dawley rats weighing approximately 250 gm were divided into four groups : control, diabetes, irradiation, and diabetes-irradiation groups. Diabetes mellitus was induced in the rats by injecting streptozotocin. Rats in control and irradiation groups were injected with citrate buffer only. After 5 days, the head and neck region of the rats in irradiation and diabetes-irradiation groups were irradiated with a single absorbed dose of 10 Gy. All the rats were sacrificed at 3, 7, 14, 21, and 28 days after irradiation. The specimen including the mandibular molars were sectioned and observed using a histopathological method. In the diabetes group, capillary dilatation was observed. However, there was no obvious morphologic alteration of the odontoblasts. In the irradiation group, generalized necrosis of the dental pulp tissues was observed. Vacuolation of the odontoblasts and dilatation of the capillaries were noted in the early experimental phases. In the diabetes-irradiation group, generalized degeneration of the dental pulp tissues was observed. Vacuolation of the dental pulp cells and the odontoblasts was noted in the late experimental phases. This experiment suggest that dilatation of the capillaries in the dental pulp tissue is induced by diabetic state, and generalized degeneration of the dental pulp tissues is induced by irradiation of the diabetic group.

A study of survival rate of the patients with esophageal carcinoma treated by pre- and/or post-operative irradiation

International Nuclear Information System (INIS)

Eida, Koichiro

1986-01-01

So far there is still considerable disagreement as to the evaluation of the pre- and postoperative irradiation effects on the survival rate of the patients with esophageal carcinoma. From April 1973 to December 1983, 138 cases of thoracic esophageal carcinoma were surgically operated upon at our Department; 68 cases were irradiated and 70 cases were not irradiated prior to the surgical operation. Followup study was done and its result has been reported in this communication. A few cases treated by pre-operative irradiation survived longer than the expected longevity in spite of their low curative operation rates. Prognosis was better in the cases with well differentiated squamous cell carcinoma, when marked or good responses to pre-operative irradiation with the calculated total dose of 30 Gy were recorded. There were differences in responsibility in the various histological types of esophageal carcinomas; good response in the group of well differentiated squamous carcinoma, less marked response in the groups of moderately and poorly differentiated squamous carcinomas, minor response in the types of undifferentiated and unclassifed carcinomas. From our observation it seems reasonable to say that prognosis of the patients with pre- and postoperative irradiation was better than that of those who received postoperative irradiation only. (author)

Damage induced in semiconductors by swift heavy ion irradiation

International Nuclear Information System (INIS)

Levalois, M.; Marie, P.

1999-01-01

The behaviour of semiconductors under swift heavy ion irradiation is different from that of metals or insulators: no spectacular effect induced by the inelastic energy loss has been reported in these materials. We present here a review of irradiation effects in the usual semiconductors (silicon, germanium and gallium arsenide). The damage is investigated by means of electrical measurements. The usual mechanisms of point defect creation can account for the experimental results. Besides, some results obtained on the wide gap semiconductor silicon carbide are reported. Concerning the irradiation effects induced by heavy ions in particle detectors, based on silicon substrate, we show that the deterioration of the detector performances can be explained from the knowledge of the substrate properties which are strongly perturbed after high doses of irradiation. Finally, some future ways of investigation are proposed. The silicon substrate is a good example to compare the irradiation effects with different particles such as electrons, neutrons and heavy ions. It is then necessary to use parameters which account for the local energy deposition, in order to describe the damage in the material

Irradiation creep induced anisotropy in a/2 dislocation populations

International Nuclear Information System (INIS)

Gelles, D.S.

1984-05-01

The contribution of anisotropy in Burgers vector distribution to irradiation creep behavior has been largely ignored in irradiation creep models. However, findings on Frank loops suggest that it may be very important. Procedures are defined to identify the orientations of a/2 Burgers vectors for dislocations in face-centered cubic crystals. By means of these procedures the anisotropy in Burgers vector populations was determined for three Nimonic PE16 pressurized tube specimens irradiated under stress. Considerable anisotropy in Burgers vector population develops during irradiation creep. It is inferred that dislocation motion during irradiation creep is restricted primarily to a climb of a/2 dislocations on 100 planes. Effect of these results on irradiation creep modeling and deformation induced irradiation growth is considered

Schistosoma mansoni: quantitative aspects of the fertility and survival of worms obtained from irradiated cercariae (3 Krad), in mice

International Nuclear Information System (INIS)

Sa Cardoso, G. de; Coelho, P.M.Z.

1990-01-01

The effect of gamma irradiation on the fertility of female mice, as well as the survival of worms in their portal system, have been observed in four groups of outbred albino mice (Mus musculus), experimentally infected with ca 450 cercariae of Schistosoma mansoni (LE and SJ strains), by transcutaneous route. The cercariae used were a) non-irradiated (control groups), and b) irradiated with 3 Krad of gamma irradiation (Co-60). From the 33 rd day on, some stability in the population of surviving worm could be observed. This population remained constant till the end of the observation period (90 th day), notedly in relation to the LE strain . Thus, it was concluded that gamma irradiation (at the dose of 3 Krad) is able to hinder the worm egg production in 98.1% of the infected mice. Further, it was observed that the few detected eggs were dead. Females were found to be more resistant to irradiation. The irradiation effect on the mortality of male worms was statistically significant scarcely from the 61 st day on. The long period of permanence of the sterile adult irradiated worms in the portal system of mice and their probable involvement in the development of immuno-protection (the so-called concomitant immunity, without the immuno-pathological involvements for the host) are here discussed. (author)

Impacts of low dose rate irradiation on the fertility, fecundity and hatchling survival of Japanese rice fish (medaka, Oryzias latipes)

International Nuclear Information System (INIS)

Hinton, T.G.; Coughlin, D.P.; Marsh, L.C.; Yi, Yi; Winn, R.

2004-01-01

A renewed international interest in the effects on biota from low dose rate irradiation has recently occurred. Much of that interest is centered on the relevance of previously accepted dose rate guidelines (e.g. 10 mGy d -1 for aquatic biota) suggested by the ICRP and IAEA. All parties concerned seem to agree that additional data are needed on population level impacts from chronic low-level exposures to radionuclides. Using a Low Dose Rate Irradiation Facility (LoDIF), we conducted an experiment on the fecundity, fertility and hatchling survival of Japanese Rice Fish (medaka, Oryzias latipes). Fish were exposed externally to 137 Cs from juvenile through adulthood at mean dose rates of 3.5, 35 and 350 mGy d -1 . Fish were bred at maturity and the following endpoints were examined: 1) the number of eggs produced; 2) the percent of eggs that hatched; and 3) the survival of hatchlings 20-days post hatch. The influence of gender was examined by breeding irradiated males with control females; control males with irradiated females; irradiated males with irradiated females; and control males with control females. The data contribute to our understanding the impacts of low dose rate irradiation. (author)

Survival and PHA-stimulation of #betta#-irradiated human peripheral blood T lymphocyte subpopulations

International Nuclear Information System (INIS)

Schwartz, J.L.; Darr, D.C.; Daulden, M.E.

1983-01-01

Human peripheral blood T lymphocyte subpopulations were identified and isolated on the basis of their ability to bind IgG (T-G), IgM (T-M), or neither immunoglobulin class (T-null). Lymphocytes were exposed to 0, 0.5, 1.0, 2.5 or 5.0 Gy of 60 Co #betta#-rays either as a T-cell suspension or as separated T cell subsets. Survival curves, determined 5 days after irradiation, revealed that each subset has radiosensitive and radioresistant portions, and that the T-G cell is the most sensitive subset. Mitotic indices of 48-h cultures showed that the response of unirradiated T lymphocytes to PHA varied greatly among the subsets, the highest indices being obtained for the T-M and the lowest for the T-G cells. With the possible exception of the T-G cells, the subsets are realtively resistant to mitotic effects of #betta#-rays. T-G cells suppress the PHA-induced mitotic response of the other T lymphocyte subsets, and this suppressor effect is radiosensitive, being abolished by 1.0 Gy. It is concluded that lymphocytes exposed to >= 1 Gy of #betta#-rays will have very few dividing B lymphocytes or T-G cells. This together with radiation-induced loss of T-G suppressor action means that the predominant lymphocyte types in mitosis after >=1 Gy are the radioresistant T-M and T-null cells. (orig.)

Survival and DNA repair in ultraviolet-irradiated haploid and diploid cultured frog cells

International Nuclear Information System (INIS)

Freed, J.J.; Hoess, R.H.; Angelosanto, F.A.; Massey, H.C. Jr.

1979-01-01

Survival and repair of DNA following ultraviolet (254-nm) radiation have been investigated in ICR 2A, a cultured cell line from haploid embryos of the grassfrog, Rana pipiens. Survival curves from cells recovering in the dark gave mean lethal dose value (D 0 ) in the range 1.5-1.7 Jm -2 for both haploid and diploid cell stocks. The only significant difference observed between haploids and diploids was in the extent of the shoulder at low fluence (Dsub(q)), the value for exponentially multiplying diploid cells (3.0 Jm -2 ) being higher than that found for haploids (1.2 Jm -2 ). Irradiation of cultures reversibly blocked in the G1 phase of the cell cycle gave survival-curve coefficients indistinguishable between haploids and diploids. Post-irradiation exposure to visible light restored colony-forming capacity and removed chromatographically estimated pyrimidine dimers from DNA at the same rates. After fluences killing 90% of the cells, complete restoration of survival was obtained after 60-min exposure to 500 foot-candles, indicating that in this range lethality is entirely photoreversible and therefore attributable to pyrimidine dimers in DNA. Dimer removal required illumination following ultraviolet exposure, intact cells and physiological temperature, implying that the photoreversal involved DNA photolyase activity. Excision-repair capacity was slight, since no loss of dimers could be detected chromoatographically during up to 48 h incubation in the dark and since autoradiographically detected 'unscheduled DNA synthesis' was limited to a 2-fold increase saturated at 10 Jm -2 . These properties make ICR 2A frog cells useful to explore how DNA-repair pathways influence mutant yield. (Auth.)

Effect of intestinal microflora on the survival time of mice exposed to lethal whole-body. gamma. irradiation

Energy Technology Data Exchange (ETDEWEB)

Onoue, M.; Uchida, K.; Yokokura, T.; Takahashi, T.; Mutai, M.

1981-11-01

The effect of intestinal microflora on the survival time of mice exposed to 2-kR whole-body ..gamma.. irradiation was studied using germfree, monoassociated, and conventionalized ICR mice. The germfree mice were monoassociated with 1 of 11 bacterial strains, which were isolated from the fresh feces of conventional mice, 2 weeks prior to irradiation. All mice died within 3 weeks after irradiation. Monoassociation with Fusobacterium sp., Streptococcus faecalis, Escherichia coli, or Pseudomonas sp. significantly reduced the mean survival time compared to that of germfree mice. In contrast, monoassociation with Clostridium sp., Bifidobacterium pseudolongum, or Lactobacillus acidophilus significantly prolonged the mean survival time compared to that of germfree mice. This suggests that the latter organisms may perform some activity to protect the mice from radiation injury. In this histopathological autopsy examination, the main lesions were hypocellularity in hematopoietic organs and hemorrhage in various organs. Neither karyorrhexis nor desquamation of intestinal mucosal cells was observed in any mice. From these observations, it is suggested that the death of these mice was related to hematopoietic damage. Bacterial invasion into various organs was observed in conventionalized and Pseudomonas-, E. coli-, or S. faecalis-monoassociated mice but not in Clostridium-, B. pseudolongum-, L. acidophilus-, or Fusobacterium-monoassociated mice.

Effect of intestinal microflora on the survival time of mice exposed to lethal whole-body γ irradiation

International Nuclear Information System (INIS)

Onoue, M.; Uchida, K.; Yokokura, T.; Takahashi, T.; Mutai, M.

1981-01-01

The effect of intestinal microflora on the survival time of mice exposed to 2-kR whole-body γ irradiation was studied using germfree, monoassociated, and conventionalized ICR mice. The germfree mice were monoassociated with 1 of 11 bacterial strains, which were isolated from the fresh feces of conventional mice, 2 weeks prior to irradiation. All mice died within 3 weeks after irradiation. Monoassociation with Fusobacterium sp., Streptococcus faecalis, Escherichia coli, or Pseudomonas sp. significantly reduced the mean survival time compared to that of germfree mice. In contrast, monoassociation with Clostridium sp., Bifidobacterium pseudolongum, or Lactobacillus acidophilus significantly prolonged the mean survival time compared to that of germfree mice. This suggests that the latter organisms may perform some activity to protect the mice from radiation injury. In this histopathological autopsy examination, the main lesions were hypocellularity in hematopoietic organs and hemorrhage in various organs. Neither karyorrhexis nor desquamation of intestinal mucosal cells was observed in any mice. From these observations, it is suggested that the death of these mice was related to hematopoietic damage. Bacterial invasion into various organs was observed in conventionalized and Pseudomonas-, E. coli-, or S. faecalis-monoassociated mice but not in Clostridium-, B. pseudolongum-, L. acidophilus-, or Fusobacterium-monoassociated mice

Xenograft survival in two species combinations using total-lymphoid irradiation and cyclosporine

International Nuclear Information System (INIS)

Knechtle, S.J.; Halperin, E.C.; Bollinger, R.R.

1987-01-01

Total lymphoid irradiation (TLI) has profound immunosuppressive actions and has been applied successfully to allotransplantation but not xenotransplantation. Cyclosporine (CsA) has not generally permitted successful xenotransplantation of organs but has not been used in combination with TLI. TLI and CsA were given alone and in combination to rats that were recipients of hamster or rabbit cardiac xenografts. Combined TLI and CsA prolonged survival of hamster-to-rat cardiac xenografts from three days in untreated controls to greater than 100 days in most recipients. TLI alone significantly prolonged rabbit to rat xenograft survival with doubling of survival time. However, combined treatment did not significantly prolong rabbit-to-rat cardiac xenograft survival compared with TLI alone. The hamster and rat are phylogenetically closely related. Transplants from hamsters to rat are concordant xenografts since the time course of unmodified rejection is similar to first-set rejection of allografts. Although the rabbit-to-rat transplant is also between concordant species (average survival of untreated controls: 3.2 days) the rabbit and rat are more distantly related. These results suggest that TLI is an effective immunosuppressant when applied to cardiac xenotransplants in these animal models; that the choice of species critically affects xenograft survival when TLI and/or CsA are used for immunosuppression; and that the closely related species combination tested has markedly prolonged (greater than 100 days) survival using combined TLI and CsA

W-reactivation of phage lambda in X-irradiated mutants of Escherichia coli K-12

Energy Technology Data Exchange (ETDEWEB)

Martignoni, K D; Haselbacher, I [Muenchen Univ. (Germany, F.R.). Strahlenbiologisches Inst.

1980-07-01

The survival of UV irradiated phage lambda was increased on X-irradiated E.coli K-12 host cells over that on unirradiated cells. The frequency of c mutants among the surviving phages was increased to a similar extent by the X-ray exposure of the host cells as by UV light. This W-reactivation of phage lambda occurred in uvrA, polA, and recB mutants besides the wild type at about equal X-ray doses, but at a reduced reactivation efficiency compared with the wild type. W-reactivation was undetectable in recA mutants. While maximal UV induced W-reactivation occured 30 min after irradiation, the maximal X-ray induced reactivation was found immediately after irradiation. Chloramphenicol (100 ..mu..g/ml) and nitrofurantoin (50 ..mu..g/ml) inhibited W-reactivation of phage lambda if added before irradiation of the host cells, indicating the necessity of protein synthesis for W-reactivation.

The Gottingen Minipig Is a Model of the Hematopoietic Acute Radiation Syndrome: G-Colony Stimulating Factor Stimulates Hematopoiesis and Enhances Survival From Lethal Total-Body γ-Irradiation

Energy Technology Data Exchange (ETDEWEB)

Moroni, Maria, E-mail: maria.moroni@usuhs.edu [Radiation Countermeasures Program, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland (United States); Ngudiankama, Barbara F. [Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland (United States); Christensen, Christine [Division of Comparative Pathology, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland (United States); Olsen, Cara H. [Biostatistics Consulting Center, Uniformed Services University of the Health Sciences, Bethesda, Maryland (United States); Owens, Rossitsa [Radiation Countermeasures Program, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland (United States); Lombardini, Eric D. [Veterinary Medicine Department, Armed Forces Research Institute of Medical Sciences, Bangkok (Thailand); Holt, Rebecca K. [Veterinary Science Department, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland (United States); Whitnall, Mark H. [Radiation Countermeasures Program, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland (United States)

2013-08-01

Purpose: We are characterizing the Gottingen minipig as an additional large animal model for advanced drug testing for the acute radiation syndrome (ARS) to enhance the discovery and development of novel radiation countermeasures. Among the advantages provided by this model, the similarities to human hematologic parameters and dynamics of cell loss/recovery after irradiation provide a convenient means to compare the efficacy of drugs known to affect bone marrow cellularity and hematopoiesis. Methods and Materials: Male Gottingen minipigs, 4 to 5 months old and weighing 9 to 11 kg, were used for this study. We tested the standard off-label treatment for ARS, rhG-CSF (Neupogen, 10 μg/kg/day for 17 days), at the estimated LD70/30 total-body γ-irradiation (TBI) radiation dose for the hematopoietic syndrome, starting 24 hours after irradiation. Results: The results indicated that granulocyte colony stimulating factor (G-CSF) enhanced survival, stimulated recovery from neutropenia, and induced mobilization of hematopoietic progenitor cells. In addition, the administration of G-CSF resulted in maturation of monocytes/macrophages. Conclusions: These results support continuing efforts toward validation of the minipig as a large animal model for advanced testing of radiation countermeasures and characterization of the pathophysiology of ARS, and they suggest that the efficacy of G-CSF in improving survival after total body irradiation may involve mechanisms other than increasing the numbers of circulating granulocytes.

The Gottingen minipig is a model of the hematopoietic acute radiation syndrome: G-colony stimulating factor stimulates hematopoiesis and enhances survival from lethal total-body γ-irradiation.

Science.gov (United States)

Moroni, Maria; Ngudiankama, Barbara F; Christensen, Christine; Olsen, Cara H; Owens, Rossitsa; Lombardini, Eric D; Holt, Rebecca K; Whitnall, Mark H

2013-08-01

We are characterizing the Gottingen minipig as an additional large animal model for advanced drug testing for the acute radiation syndrome (ARS) to enhance the discovery and development of novel radiation countermeasures. Among the advantages provided by this model, the similarities to human hematologic parameters and dynamics of cell loss/recovery after irradiation provide a convenient means to compare the efficacy of drugs known to affect bone marrow cellularity and hematopoiesis. Male Gottingen minipigs, 4 to 5 months old and weighing 9 to 11 kg, were used for this study. We tested the standard off-label treatment for ARS, rhG-CSF (Neupogen, 10 μg/kg/day for 17 days), at the estimated LD70/30 total-body γ-irradiation (TBI) radiation dose for the hematopoietic syndrome, starting 24 hours after irradiation. The results indicated that granulocyte colony stimulating factor (G-CSF) enhanced survival, stimulated recovery from neutropenia, and induced mobilization of hematopoietic progenitor cells. In addition, the administration of G-CSF resulted in maturation of monocytes/macrophages. These results support continuing efforts toward validation of the minipig as a large animal model for advanced testing of radiation countermeasures and characterization of the pathophysiology of ARS, and they suggest that the efficacy of G-CSF in improving survival after total body irradiation may involve mechanisms other than increasing the numbers of circulating granulocytes. Published by Elsevier Inc.

The Gottingen Minipig Is a Model of the Hematopoietic Acute Radiation Syndrome: G-Colony Stimulating Factor Stimulates Hematopoiesis and Enhances Survival From Lethal Total-Body γ-Irradiation

International Nuclear Information System (INIS)

Moroni, Maria; Ngudiankama, Barbara F.; Christensen, Christine; Olsen, Cara H.; Owens, Rossitsa; Lombardini, Eric D.; Holt, Rebecca K.; Whitnall, Mark H.

2013-01-01

Purpose: We are characterizing the Gottingen minipig as an additional large animal model for advanced drug testing for the acute radiation syndrome (ARS) to enhance the discovery and development of novel radiation countermeasures. Among the advantages provided by this model, the similarities to human hematologic parameters and dynamics of cell loss/recovery after irradiation provide a convenient means to compare the efficacy of drugs known to affect bone marrow cellularity and hematopoiesis. Methods and Materials: Male Gottingen minipigs, 4 to 5 months old and weighing 9 to 11 kg, were used for this study. We tested the standard off-label treatment for ARS, rhG-CSF (Neupogen, 10 μg/kg/day for 17 days), at the estimated LD70/30 total-body γ-irradiation (TBI) radiation dose for the hematopoietic syndrome, starting 24 hours after irradiation. Results: The results indicated that granulocyte colony stimulating factor (G-CSF) enhanced survival, stimulated recovery from neutropenia, and induced mobilization of hematopoietic progenitor cells. In addition, the administration of G-CSF resulted in maturation of monocytes/macrophages. Conclusions: These results support continuing efforts toward validation of the minipig as a large animal model for advanced testing of radiation countermeasures and characterization of the pathophysiology of ARS, and they suggest that the efficacy of G-CSF in improving survival after total body irradiation may involve mechanisms other than increasing the numbers of circulating granulocytes

Stem-spermatogonial survival and incidence of reciprocal translocations in the γ-irradiated boar

International Nuclear Information System (INIS)

Erickson, B.H.; Martin, P.G.

1984-01-01

To assess the effects of γ-radiation on stem-cell survival and incidence of reciprocal translocations, boar testes were irradiated with 100, 200, or 400 rad. Stem-cell survival was markedly affected by 100 rad (51% of control) and reduced to 34% of control by 400 rad. Production of differentiating spermatogonia renewal was incomplete at 12 weeks. Incidence of translocations peaked at 200 rad and the number occurring at 100 and 400 rad was similar. Kinetics of porcine spermatogonial renewal differs considerably from those of the rodent and, relative to the rodent, this may account for the boar's higher sensitivity to stem-cell killing and lower sensitivity to translocation

In situ X-ray diffraction study of irradiation-induced lattice expansion in Al foils by MeV-energy heavy ions

Energy Technology Data Exchange (ETDEWEB)

Minagawa, Hideaki [Department of Nuclear Engineering, Kyoto University, Kyoto 615-8530 (Japan); Tsuchida, Hidetsugu, E-mail: tsuchida@nucleng.kyoto-u.ac.jp [Department of Nuclear Engineering, Kyoto University, Kyoto 615-8530 (Japan); Quantum Science and Engineering Center, Kyoto University, Uji 611-0011 (Japan); Murase, Ryu [Department of Nuclear Engineering, Kyoto University, Kyoto 615-8530 (Japan); Itoh, Akio [Department of Nuclear Engineering, Kyoto University, Kyoto 615-8530 (Japan); Quantum Science and Engineering Center, Kyoto University, Uji 611-0011 (Japan)

2016-04-01

Using in situ X-ray diffraction measurements, we investigate lattice deformations of a free-standing aluminum foil induced by irradiation with MeV-energy heavy projectiles (C, O, and Si ions). The dependence of the ion-beam flux on the lattice expansion is analyzed in terms of two types of irradiation effects: (i) electronic excitation collision-induced lattice heating and (ii) elastic collision-induced displacement damage. We observe that the change in the lattice parameter is proportional to the energy in lattice heating, irrespective of projectile species. This result is in good agreement with a model calculation for thermal lattice expansion caused by beam heating. Moreover, with the correlation between lattice expansion and displacement damage, we consider a simple model for lattice expansion originating from the accumulation of Frenkel defects. From the model, we obtained the relationship between the relative changes in lattice parameter and the value of displacement per atom (dpa) rate. A comparison of the results from model calculations and experiments shows that the dpa rate calculated from the model, which takes account of athermal defect-recombination, is strongly correlated with the change in lattice parameter. This result suggests that the concentration of surviving defects under irradiation diminishes because of spontaneous recombination of defects produced.

Protective effects of vitamin C against gamma-ray induced wholly damage and genetic damage

International Nuclear Information System (INIS)

Fu Chunling; Jiang Weiwei; Zhang Ping; Chen Xiang; Zhu Shengtao

2000-01-01

Objective: Protective effects of supplemental vitamin C against 60 Co-gamma-ray induced wholly damage and genetic damage was investigated in mice. Method: Mice were divided into normal control group, irradiation control group and vitamin C experimental group 1,2,3 (which were orally given vitamin C 15, 30, 45 mg/kg.bw for 10 successive days respectively prior to gamma-ray irradiation). Micronuclei in the bone marrow polychromatophilic erythrocytes in each group of mice were examined and the 30 day survival rate of mice following whole-body 5.0 Gy γ irradiation were also determined. Results: Supplemental vitamin C prior to gamma-rays irradiation can significantly decrease bone marrow PECMN rate of mice and increase 30 day survival rate and prolong average survival time. The protection factor is 2.09. Conclusion: Vitamin C has potent protective effects against gamma irradiation induced damage in mice. In certain dose range, vitamin C can absolutely suppress the gamma-rays induced genetic damage in vivo

Search for the lowest irradiation dose from literatures on radiation-induced breast cancer

Energy Technology Data Exchange (ETDEWEB)

Yoshizawa, Y; Kusama, T [Tokyo Univ. (Japan). Faculty of Medicine

1975-12-01

A survey of past case reports concerning radiation-induced breast cancer was carried out in order to find the lowest irradiation dose. The search of literature published since 1951 revealed 10 cases of radiation-induced breast cancer. Only 5 cases had precise descriptions of the irradiation dose. The lowest irradiation dose was estimated at 1470 rads in the case of external X-ray irradiation for tuberous angioma. All of cases of radiation-induced breast cancer had received radiation for the treatment of nonmalignant tumors, such as pulmonary tuberculosis, mastitis, and tuberous angioma. There also were three statistical studies. The first concerned atomic bomb survivors, the second, pulmoanry tuberculous patients subjected to frequent fluoroscopies, and the third, patients of acute post partum mastitis. These statistical studies had revealed a significant increase in the incidence of breast cancer in the irradiated group, but there was little information about the lowest irradiation dose. It was noticed that radiation-induced breast cancer was more numerous in the upper inner quadrant of the breast. Most histopathological findings of radiation-induced breast cancer involved duct cell carcinoma. The latent period was about 15 years.

Edaravone protects human peripheral blood lymphocytes from γ-irradiation-induced apoptosis and DNA damage.

Science.gov (United States)

Chen, Liming; Liu, Yinghui; Dong, Liangliang; Chu, Xiaoxia

2015-03-01

Radiation-induced cellular injury is attributed primarily to the harmful effects of free radicals, which play a key role in irradiation-induced apoptosis. In this study, we investigated the radioprotective efficacy of edaravone, a licensed clinical drug and a powerful free radical scavenger that has been tested against γ-irradiation-induced cellular damage in cultured human peripheral blood lymphocytes in studies of various diseases. Edaravone was pre-incubated with lymphocytes for 2 h prior to γ-irradiation. It was found that pretreatment with edaravone increased cell viability and inhibited generation of γ-radiation-induced reactive oxygen species (ROS) in lymphocytes exposed to 3 Gy γ-radiation. In addition, γ-radiation decreased antioxidant enzymatic activity, such as superoxide dismutase and glutathione peroxidase, as well as the level of reduced glutathione. Conversely, treatment with 100 μM edaravone prior to irradiation improved antioxidant enzyme activity and increased reduced glutathione levels in irradiated lymphocytes. Importantly, we also report that edaravone reduced γ-irradiation-induced apoptosis through downregulation of Bax, upregulation of Bcl-2, and consequent reduction of the Bax:Bcl-2 ratio. The current study shows edaravone to be an effective radioprotector against γ-irradiation-induced cellular damage in lymphocytes in vitro. Finally, edaravone pretreatment significantly reduced DNA damage in γ-irradiated lymphocytes, as measured by comet assay (% tail DNA, tail length, tail moment, and olive tail moment) (p edaravone offers protection from radiation-induced cytogenetic alterations.

Effects of chronic γ-irradiation on growth and survival of the Tohoku hynobiid salamander, Hynobius lichenatus

Energy Technology Data Exchange (ETDEWEB)

Fuma, Shoichi [Project for Environmental Dynamics and Radiation Effects, Fukushima Project Headquarters, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 Japan (Japan); Une, Yumi [Laboratory of Veterinary Pathology, School of Veterinary Medicine, Azabu University, 1-17-71 Fuchinobe, Sagamihara, Kanagawa 252-5201 (Japan); Ihara, Sadao [Hokkaido University of Education Kushiro Campus, 1-15-55 Shiroyama, Kushiro, Hokkaido 085-8580 Japan (Japan); Matsui, Kumi [Laboratory of Veterinary Physiology 1, School of Veterinary Medicine, Azabu University, 1-17-71 Fuchinobe, Sagamihara, Kanagawa 252-5201 (Japan); Kudo, Tomoo; Tokiwa, Toshihiro [Laboratory of Veterinary Pathology, School of Veterinary Medicine, Azabu University, 1-17-71 Fuchinobe, Sagamihara, Kanagawa 252-5201 (Japan); Kubota, Yoshihisa; Soeda, Haruhi [Project for Environmental Dynamics and Radiation Effects, Fukushima Project Headquarters, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 Japan (Japan); Ishikawa, Takahiro [Department of Technical Support and Development, Research, Development and Support Centre, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 Japan (Japan); Doi, Kazutaka [Project for Human Health, Fukushima Project Headquarters, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 Japan (Japan); Watanabe, Yoshito; Yoshida, Satoshi [Project for Environmental Dynamics and Radiation Effects, Fukushima Project Headquarters, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 Japan (Japan)

2014-09-15

The Tohoku hynobiid salamanders, Hynobius lichenatus, were chronically irradiated with γ-rays from embryonic to juvenile stages for 450 days. At 490 μGy h{sup −1} or lower dose rates, growth and survival were not significantly affected by irradiation, and any morphological aberrations and histological damages were not observed. At 4600 μGy h{sup −1}, growth was severely inhibited, and all the individuals died mostly at the juvenile stage. Chronic LD{sub 50} was 42 Gy as a total dose. In the liver, the number of hematopoietic cells was significantly reduced in the living juveniles, and these cells disappeared in the dead juveniles. In the spleen, mature lymphocytes were depleted in the living larvae, and almost all the heamtopoietic cells disappeared in the dead juveniles. These results suggest that this salamander died due to acute radiation syndrome, i.e., hematopoietic damage and subsequent sepsis caused by immune depression. The death would be also attributed to skin damage inducing infection. At 18,000 μGy h{sup −1}, morphological aberrations and severe growth inhibition were observed. All the individuals died at the larval stage due to a multiple organ failure. Chronic LD{sub 50} was 28 Gy as a total dose. Assuming that chronic LD{sub 50} was 42 Gy at lower dose rates than 4600 μGy h{sup −1}, a chronic median lethal dose rate could be estimated to be <340 μGy h{sup −1} for the whole life (>14 years). These results suggest that, among guidance dose rates, i.e., 4–400 μGy h{sup −1}, proposed by various organisations and research programmes for protection of amphibians and taxonomic groups or ecosystems including amphibians, most of them would protect this salamander but the highest value may not on the whole life scale. - Highlights: • The salamanders, Hynobius lichenatus, were chronically γ-irradiated for 450 days. • At 490 μGy h{sup −1} or lower, irradiation did not significantly affect growth and survival. • All the individuals

Mathematical simulation of influence of irradiated cell reparative system saturation on cell survival. Communication 1. Simulation of survival curves in prokaryotes

International Nuclear Information System (INIS)

Knyigavko, V.G.; Meshcheryakova, O.P.; Radzyishevs'ka, Je.B.

2004-01-01

Mathematical models of the processes of forming survival curves for prokaryotes which are based on the idea about the possibility of saturation of radiation lesion reparation systems of DNA of the irradiated cells at the dose increase were worked out. For the simplest of the discussed models the authors discuss the question about the methods of evaluation of the model parameters

Protective effect of hypoxia in the ram testis during single and split-dose X-irradiation

International Nuclear Information System (INIS)

Vliet, J. van; Wensing, C.J.G.; Bootsma, A.L.; Peperzeel, H.A. van; Schipper, J.

1988-01-01

Spertogonial stem-cell survival in the ram was studied after single (6Gy) and split-dose X-irradiation both under normal and hypoxic conditions. Hypoxia was induced by inflation of an occluder implanted around the testicular artery. The occluders were inflated about 10 min before irradiation and deflated immediately after. Stem-cell survival was measured at 5 or 7 weeks after irradiation by determination of the Repopulation Index (RI) in histological testis sections. The RI-values after fractionated irradiation were only half those after single dose irradiation. Hypoxia had a protective effect on the stem-cell survival. After split-dose irradiation under hypoxic conditions two times more stem cells survived than under normal oxic conditions; the RI-values increased from 34% (oxic) to 68% (hypoxic). This effect of hypoxia was also found after single dose irradiation where the RI-values increased from 68% (oxic) to 84% (hypoxic). The development of the epithelium in repopulated tubules was also studied. Under hypoxia, a significantly higher fraction of tubules with complete epithelium was found after single (38 vs. 4%) as well as after split-dose irradiation (12 vs. 0%)

Preliminary examination of induced radio activity in pepper by 10 MeV electron irradiation

International Nuclear Information System (INIS)

Furuta, Masakazu; Katayama, Tadashi; Ito, Norio; Mizohata, Akira; Matsunami, Tadao; Toratani, Hirokazu; Takeda, Atsuhiko

1989-01-01

β-ray measurement was performed on 10 MeV electron-irradiated black pepper and white pepper in order to reconfirm the wholesomeness of irradiated food and present unambiguous data to general consumers concerning about the induced radioactivity in the irradiated foods. From elemental composition of the samples and investigation of photonuclear reactions, several β-emmitters were listed up. But no radioactivity other than from natural sources was detected in the irradiated sample by β-ray counting with 2 π gass flow counter, suggesting that the induced β-emmitters in the irradiated sample was below the detection limit of its induced radioactivity. (author)

A single dose of an inhibitor of cyclooxygenase 2, meloxicam, administered shortly after irradiation increases survival of lethally irradiated mice

Czech Academy of Sciences Publication Activity Database

Hofer, Michal; Pospíšil, Milan; Dušek, L.; Hoferová, Zuzana; Weiterová, Lenka

2011-01-01

Roč. 176, č. 2 (2011), s. 269-272 ISSN 0033-7587 R&D Projects: GA ČR(CZ) GA305/08/0158 Grant - others:GA ČR(CZ) GAP303/11/0128 Program:GA Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : cyclooxygenase-2 inhibition * lethal irradiation * survival Subject RIV: BO - Biophysics Impact factor: 2.684, year: 2011

Irradiation deformation due to SIPA induced dislocation anisotropy

International Nuclear Information System (INIS)

Woo, CH.

1980-02-01

A contribution to irradiation deformation resulting from the stress-induced preferred adsorption (SIPA) effect is considered. SIPA causes a variation of the growth rates of irradiation-generated dislocation loops, according to the alignment of their Burgers vectors with respect to the applied stress. A prolinged period under an applied stress then creates an anisotropic dislocation structure in which the majority of dislocations have their Burgers vectors in alignment with the stress. In the presence of 'neutral' sinks, the resulting anisotropic dislocation structure causes plastic deformation similar to the way in which irradiation growth occurs in zirconium. This mechanism is called SIPA-induced growth (SIG). We have shown that SIG is very significant in comparison to SIPA, except when little or no loop growth has occurred during the period the stress is applied. This report contains the detailed formulation and derivation of the formulae for the evaluation of the contribution due to SIG. (auth)

Radiation-induced organogenesis: effects of irradiated medium and its components on tobacco tissue culture

International Nuclear Information System (INIS)

Degani, N.

1975-01-01

Gamma irradiated medium induces the formation of buds in non-irradiated dark growth tobacco callus (Nicotiana tabacum Var. Wisconsin No.38). Experiments were conducted to determine the component(s) of the medium that is effective in this radiation-induced organogenesis. Fraction of medium were irradiated singly and in combination, then combined with non-irradiated fractions to form the complete growth medium. The results showed that irradiated indoleacetic acid (IAA) was not the effective component in the induction of organogensis. Omission of IAA from the medium resulted in the formation of buds, as expected. Irradiated myo-inositol induced organogenesis more consistently than the other irradiated components. The age of the inoculum tissue and its passage number from the tobacco stem affected the potency of the tobacco callus to organise. (author)

Rodent malaria: BCG-induced protection and immunosuppression

International Nuclear Information System (INIS)

Smrkovski, L.L.; Strickland, G.T.

1978-01-01

One dose of 10 7 viable units of Mycobacterium bovis, strain BCG, protected a significant number of Swiss mice from a primary challenge with 10 4 thoracic sporozoites of Plasmodium berghei. Immunization with irradiated sporozoites induced greater protection than that observed in BCG-treated animals. Mice treated with BCG and surviving a primary sporozoite challenge were not protected from rechallenge, whereas mice immunized with irradiated sporozoites and surviving initial challenge of sporozoites were solidly immune to further challenge. Immunizing mice with BCG and irradiated sporozoites simulataneously resulted in a synergistic effect of increased protection against a primary challenge of sporozoites only if the two immunogens were administered on the same day and if the mice were challenged 1 to 3 days later. Mice given BCG and irradiated sporozoites and surviving a primary challenge of sporozoites were unable to survive rechallenge. BCG given to mice previously immunized with irradiated sporozoites suppressed their protective immunity against sporozoite challenge

Effect of irradiation on the periodontal tissues in streptozotocin-induced diabetic rats

International Nuclear Information System (INIS)

Park, Dong Sin; Hwang, Eui Hwan; Lee, Sang Rae

2005-01-01

To observe the histopathological changes in the periodontal tissues of mandibular molars in streptozotocin-induced diabetic rats after irradiation. The male Sprague-Dawley rats weighing approximately 250 gm were divided into four groups; control, diabetes, irradiation, and diabetes - irradiation groups. Diabetes mellitus was induced in the rats by injecting streptozotocin. Rats in the control and irradiation groups were injected with citrate buffer only. After 5 days, the head and neck region of the rats in irradiation and diabetes - irradiation groups were irradiated with a single absorbed dose of 10 Gy. All the rats were sacrificed at 3, 7, 14, 21, and 28 days after irradiation. The specimen including the mandibular molars were sectioned and observed using a histopathological method. In the diabetes group, osteoclastic activity was observed in the alveolar bone and the root throughout the period of experiment. Also, osteoblastic and fibroblastic activities were markedly decreased. In the irradiation group, the osteoclasts were observed in the alveolar bone and the dilated capillaries were increased in the early experimental phases. However, vigorous osteoblastic activity was noted in the late experimental phases. In the diabetes- irradiation group, osteoblastic activity in the alveolar bone and the root was observed in the early experimental phases. However, there were no resorption and osteoblastic activity in the alveolar bone and the root in the late experimental phases, and obvious atrophic change of fibrous tissues was noted. This experiment suggests that osteoblastic activity was caused by irradiation in the late experimental phases, but atrophic change of the periodontal ligament tissues was induced after irradiation in diabetic state.

Effects of cell concentrations on the survival and repopulation of haemopoietic stem cells in irradiated bone marrow cell culture in vitro

International Nuclear Information System (INIS)

Fujitake, Hideki; Okamoto, Yuruko; Okubo, Hiroshi; Miyanomae, Takeshi; Kumagai, Keiko; Mori, K.J.

1981-01-01

Effects of cell concentrations on the survival and repopulation of haemopoietic stem cells after irradiation were studied in the long-term culture of mouse bone marrow cells in vitro. No difference was observed in the survival of the stem cells among cultures in which 0 - 10 7 cells were re-inoculated on the adherent cell colonies in the culture flask. Stem cells showed a significant proliferation within 1 week and the number of the stem cells exceeded the control in 3 weeks after irradiation in the cultures with less than 10 6 re-inoculated cells per flask. In contrast, there was a considerable delay in the onset of stem cell proliferation after irradiation in the culture with 10 7 cells per flask. Based on these results, a possibility that a stimulator of stem cell proliferation, released from irradiated stromal cells, is cancelled by an inhibitory factor produced by irradiated or unirradiated haemopoietic cells is postulated. (author)

Exogenous HGF Bypasses the Effects of ErbB Inhibition on Tumor Cell Viability in Medulloblastoma Cell Lines

NARCIS (Netherlands)

Zomerman, Waldrik W; Plasschaert, Sabine L. A.; Diks, Sander H.; Lourens, Harm-Jan; Meeuwsen-de Boer, Tiny; Hoving, Eelco W.; den Dunnen, Wilfred F. A.; de Bont, Eveline S. J. M.

2015-01-01

Recent clinical trials investigating receptor tyrosine kinase (RTK) inhibitors showed a limited clinical response in medulloblastoma. The present study investigated the role of micro-environmental growth factors expressed in the brain, such as HGF and EGF, in relation to the effects of hepatocyte

Characterization of irradiation induced deep and shallow impurities

Science.gov (United States)

Treberspurg, Wolfgang; Bergauer, Thomas; Dragicevic, Marko; Krammer, Manfred; Valentan, Manfred

2013-12-01

Silicon Detectors close to the interaction point of the High Luminosity Large Hardron Collider (HL-LHC) have to withstand a harsh irradiation environment. In order to evaluate the behaviour of shallow and deep defects, induced by neutron irradiation, spreading resistance resistivity measurements and capacitance voltage measurements have been performed. These measurements, deliver information about the profile of shallow impurities after irradiation as well as indications of deep defects in the Space Charge Region (SCR) and the Electrical Neutral Bulk (ENB). By considering the theoretical background of the measurement both kinds of defects can be investigated independently from each other.

Characterization of irradiation induced deep and shallow impurities

Energy Technology Data Exchange (ETDEWEB)

Treberspurg, Wolfgang, E-mail: wolfgang.treberspurg@oeaw.ac.at; Bergauer, Thomas; Dragicevic, Marko; Krammer, Manfred; Valentan, Manfred

2013-12-21

Silicon Detectors close to the interaction point of the High Luminosity Large Hardron Collider (HL-LHC) have to withstand a harsh irradiation environment. In order to evaluate the behaviour of shallow and deep defects, induced by neutron irradiation, spreading resistance resistivity measurements and capacitance voltage measurements have been performed. These measurements, deliver information about the profile of shallow impurities after irradiation as well as indications of deep defects in the Space Charge Region (SCR) and the Electrical Neutral Bulk (ENB). By considering the theoretical background of the measurement both kinds of defects can be investigated independently from each other.

Characterization of irradiation induced deep and shallow impurities

International Nuclear Information System (INIS)

Treberspurg, Wolfgang; Bergauer, Thomas; Dragicevic, Marko; Krammer, Manfred; Valentan, Manfred

2013-01-01

Silicon Detectors close to the interaction point of the High Luminosity Large Hardron Collider (HL-LHC) have to withstand a harsh irradiation environment. In order to evaluate the behaviour of shallow and deep defects, induced by neutron irradiation, spreading resistance resistivity measurements and capacitance voltage measurements have been performed. These measurements, deliver information about the profile of shallow impurities after irradiation as well as indications of deep defects in the Space Charge Region (SCR) and the Electrical Neutral Bulk (ENB). By considering the theoretical background of the measurement both kinds of defects can be investigated independently from each other

Significant prolongation of segmental pancreatic allograft survival in two species

Energy Technology Data Exchange (ETDEWEB)

Du Toit, D.F.; Heydenrych, J.J.

1988-06-01

A study was conducted to assess the suppression of segmental pancreatic allograft rejection by cyclosporine (CSA) alone in baboons and dogs, and subtotal marrow irradiation (TL1) alone and TL 1 in combination with CSA in baboons. Total pancreatectomy in the dog and primate provided a reliable diabetic model, induced an absolute deficiency of insulin and was uniformly lethal if not treated. Continuous administration of CSA in baboons resulted in modest allograft survival. As in baboons, dogs receiving CSA 25 mg/kg/d rendered moderate graft prolongation but a dose of 40 mg/kg/d resulted in significant graft survival (greater than 100 days) in 5 of 8 allograft recipients. Irradiation alone resulted in minimal baboon pancreatic allograft survival of 20 baboons receiving TL1 1,000 rad and CSA, 3 had graft survival greater than of 100 days. Of 15 baboons receiving TL1 800 rad and CSA, 6 had graft survival of greater than 100 days. In conclusion, CSA administration in dogs and TL1 in combination with CSA in baboons resulted in highly significant segmental pancreatic allograft survival.

Significant prolongation of segmental pancreatic allograft survival in two species

International Nuclear Information System (INIS)

Du Toit, D.F.; Heydenrych, J.J.

1988-01-01

A study was conducted to assess the suppression of segmental pancreatic allograft rejection by cyclosporine (CSA) alone in baboons and dogs, and subtotal marrow irradiation (TL1) alone and TL 1 in combination with CSA in baboons. Total pancreatectomy in the dog and primate provided a reliable diabetic model, induced an absolute deficiency of insulin and was uniformly lethal if not treated. Continuous administration of CSA in baboons resulted in modest allograft survival. As in baboons, dogs receiving CSA 25 mg/kg/d rendered moderate graft prolongation but a dose of 40 mg/kg/d resulted in significant graft survival (greater than 100 days) in 5 of 8 allograft recipients. Irradiation alone resulted in minimal baboon pancreatic allograft survival of 20 baboons receiving TL1 1,000 rad and CSA, 3 had graft survival greater than of 100 days. Of 15 baboons receiving TL1 800 rad and CSA, 6 had graft survival of greater than 100 days. In conclusion, CSA administration in dogs and TL1 in combination with CSA in baboons resulted in highly significant segmental pancreatic allograft survival

Survival of very young children with medulloblastoma (primitive neuroectodermal tumor of the posterior fossa) treated with craniospinal irradiation

International Nuclear Information System (INIS)

Saran, Frank H.; Driever, Pablo Herniz; Thilmann, Christoph; Mose, Stephan; Wilson, Paula; Sharpe, Geoff; Adamietz, Irenaeus A.; Boettcher, Heinz D.

1998-01-01

Purpose: Very young children with medulloblastoma are considered to have a worse prognosis than older children. As radiotherapy remains an important part of the treatment, the adverse prognosis could be due to inadequate radiation treatment rather than biological factors. We analyzed the published literature to examine the impact of radiotherapy on survival in this group. Methods and Materials: A Medline search was performed and we reviewed studies of treatment of medulloblastoma where radiotherapy was delivered using megavoltage equipment and the minimum follow-up allowed the calculation of 5-year survival rates. Results: Thirty-nine studies were published between 1979 and 1996 with a treatment including craniospinal irradiation and boost to the posterior fossa. Eleven studies comprising 1366 patients analyzed survival by age at diagnosis. Eight of 11 studies showed a worse 5-year survival for the younger patient group which reached statistical significance in two. There is also a suggestion of a higher proportion of children with metastatic disease at presentation in the very young age group. The usual policy in younger children was to give a lower dose of radiotherapy to the craniospinal axis (CSA) and posterior fossa (PF) with reduction of dose in the range of 15 to 25% compared to standard treatment. As dose reduction to the posterior fossa is associated with worse survival and local recurrence is the predominant site of failure, the major determinant of worse survival in very young children with medulloblastoma may be suboptimal radiotherapy. Protocols including postoperative chemotherapy with delayed, omitted, or only local tumor irradiation do not reach survival rates of protocols with standard radiotherapy, also suggesting a continued importance for irradiation. Conclusion: Very young children with medulloblastoma have a worse prognosis than older children. Inadequate radiation dose and technique to the primary tumor region may be a major contributing

Evaluation of induced radioactivity in 10 MeV electron-irradiated spices

Energy Technology Data Exchange (ETDEWEB)

Furuta, Masakazu; Ito, Norio; Mizohata, Akira; Matsunami, Tadao; Katayama, Tadashi; Toratani, Hirokazu (Osaka Prefectural Univ., Sakai (Japan). Research Inst. for Advanced Science and Technology); Takeda, Atsuhiko

1993-10-01

In order to make clear appreciation to induced radioactivity in the irradiated foods, photonuclear reactions which could produce radioactivity at energies up to 10 MeV were listed up from elemental compositions of black pepper, white pepper, red pepper, ginger and turmeric. The samples were irradiated with 10 MeV electron from a linear accelerator to a dose of 100 kGy and radioactivity was measured. Induced radioactivity could not be detected significantly by gamma-ray spectrometry and beta-ray counting in the irradiated samples except for spiked samples which contain some photonuclear target nuclides in the list. From the amount of observed radioactivities of short-lived photonuclear products in the spiked samples and calculation of H[sub 50] according to ICRP Publication 30, it was concluded that the induced radioactivity and its biological effects in the 10 MeV electron-irradiated natural samples were negligible in comparison with natural radioactivity from [sup 40]K contained in the samples. (J.P.N.).

Survival and photoreactivability of ultraviolet-irradiated cultured fish cells (CAF-MM1)

International Nuclear Information System (INIS)

Mano, Y.; Mitani, H.; Etoh, H.; Egami, N.

1980-01-01

The sensitivity to ultraviolet light (uv) and photoreactivating ability of cultured fish clone cells (CAF-MM1) were investigated. Dose-survival relationship curves were obtained using the colony-forming technique at various postirradiation temperatures (33, 26, and 20 0 C). At 26 0 C the values of D 0 , D/sub q/, and the extrapolation number (n) were 1.74 J/m 2 , 2.62 J/m 2 , and 4.5, respectively; no marked differences in these values were found among different temperatures. Visible light illumination after uv irradiation produced a marked increase in survival. No photoreactivation effects were observed beyond about 30 h. Caffeine increased uv sensitivity of the CAF-MM1 cells, and from the results it is suggested that the cells have some caffeine-sensitive dark repair mechanisms

Survival curves for irradiated cells

International Nuclear Information System (INIS)

Gibson, D.K.

1975-01-01

The subject of the lecture is the probability of survival of biological cells which have been subjected to ionising radiation. The basic mathematical theories of cell survival as a function of radiation dose are developed. A brief comparison with observed survival curves is made. (author)

Heavy ion irradiation induces autophagy in irradiated C2C12 myoblasts and their bystander cells

International Nuclear Information System (INIS)

Hino, Mizuki; Tajika, Yuki; Hamada, Nobuyuki

2010-01-01

Autophagy is one of the major processes involved in the degradation of intracellular materials. Here, we examined the potential impact of heavy ion irradiation on the induction of autophagy in irradiated C2C12 mouse myoblasts and their non-targeted bystander cells. In irradiated cells, ultrastructural analysis revealed the accumulation of autophagic structures at various stages of autophagy (id est (i.e.) phagophores, autophagosomes and autolysosomes) within 20 min after irradiation. Multivesicular bodies (MVBs) and autolysosomes containing MVBs (amphisomes) were also observed. Heavy ion irradiation increased the staining of microtubule-associated protein 1 light chain 3 and LysoTracker Red (LTR). Such enhanced staining was suppressed by an autophagy inhibitor 3-methyladenine. In addition to irradiated cells, bystander cells were also positive with LTR staining. Altogether, these results suggest that heavy ion irradiation induces autophagy not only in irradiated myoblasts but also in their bystander cells. (author)

Fundamental Studies of Irradiation-Induced Modifications in Microstructural Evolution and Mechanical Properties of Advanced Alloys

Energy Technology Data Exchange (ETDEWEB)

Stubbins, James; Heuser, Brent; Hosemann, Peter; Liu, Xiang

2018-04-24

segregation (RIS) of Ni and Si was observed in both A709 and 316H in all irradiated conditions and was found at various sinks: line dislocations, dislocation loops, void surfaces, carbide-matrix interfaces, etc. Radiation also induced the formation of Ni,Si-rich precipitates. As suggested in a previous study on neutron-irradiated 316 stainless steel, one possible consequence of the significant RIS of Si is that the enrichment at defect sinks depletes the silicon in the matrix, which can lead to enhanced void nucleation rate. The enrichment of Ni and Si is accompanied by the depletion of Cr at defect sinks, which could also affect the corrosion resistance. Radiation-induced change in the orientation relationship of pre-existing MX precipitates was observed at 600°. It is believed that this change is associated with the network dislocations formed under irradiation. The underlying mechanism is still not well understood. This change could be a positive indication that the MX precipitates can survive high density network dislocations. It would be helpful if neutron irradiation at similar dose conditions could be carried out to verify that this effect is not unique for ion irradiation. Intragranular Cr-rich carbides with a core-shell structure, i.e. Cr-rich carbide core and Ni,Si-rich shell was found at 500° and 600° in the highest dose (150 peak dpa) specimens. Coarse voids (30 nm in diameter) were only commonly found at 500° in the 50 and 150 peak dpa specimens in regions less than 750 nm in depth. The highest swelling for A709 irradiated to 50 and 150 peak dpa at 500° is about 0.44% and 0.37%, respectively. Due to the choice of 100 degree temperature intervals, this study did not attempt to precisely identify peak void swelling conditions, merely the range of irradiation temperatures where this could be a concern. It is known high-dose ion irradiation can significantly suppress void nucleation. Future neutron irradiation in the 500–600° range (without considering the

Effect of gamma irradiation on Burkholderia thailandensis (Burkholderia pseudomallei surrogate) survival under combinations of pH and NaCl

Energy Technology Data Exchange (ETDEWEB)

Yoon, Yohan; Kim, Jae-Hun; Byun, Myung-Woo [Team for Radiation Food Science and Biotechnology, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup, Jeollabuk 580-185 (Korea, Republic of); Choi, Kyoung-Hee [Department of Oral Microbiology, College of Dentistry, Wonkwang University, Iksan, Jeollabuk 570-749 (Korea, Republic of); Lee, Ju-Woon, E-mail: sjwlee@kaeri.re.k [Team for Radiation Food Science and Biotechnology, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup, Jeollabuk 580-185 (Korea, Republic of)

2010-04-15

This study evaluated the effect of gamma irradiation on Burkholderia thailandensis (Burkholderia pseudomallei surrogate; potential bioterrorism agent) survival under different levels of NaCl and pH. B. thailandensis in Luria Bertani broth supplemented with NaCl (0-3%), and pH-adjusted to 4-7 was treated with gamma irradiation (0-0.5 kGy). Surviving cell counts of bacteria were then enumerated on tryptic soy agar. Data for the cell counts were also used to calculate D{sub 10} values (the dose required to reduce 1 log CFU/mL of B. thailandensis). Cell counts of B. thailandensis were decreased (P<0.05) as irradiation dose increased, and no differences (P>=0.05) in cell counts of the bacteria were observed among different levels of NaCl and pH. D{sub 10} values ranged from 0.04 to 0.07 kGy, regardless of NaCl and pH level. These results indicate that low doses of gamma irradiation should be a useful treatment in decreasing the potential bioterrorism bacteria, which may possibly infect humans through foods.

Effect of gamma irradiation on Burkholderia thailandensis ( Burkholderia pseudomallei surrogate) survival under combinations of pH and NaCl

Science.gov (United States)

Yoon, Yohan; Kim, Jae-Hun; Byun, Myung-Woo; Choi, Kyoung-Hee; Lee, Ju-Woon

2010-04-01

This study evaluated the effect of gamma irradiation on Burkholderia thailandensis ( Burkholderia pseudomallei surrogate; potential bioterrorism agent) survival under different levels of NaCl and pH. B. thailandensis in Luria Bertani broth supplemented with NaCl (0-3%), and pH-adjusted to 4-7 was treated with gamma irradiation (0-0.5 kGy). Surviving cell counts of bacteria were then enumerated on tryptic soy agar. Data for the cell counts were also used to calculate D10 values (the dose required to reduce 1 log CFU/mL of B. thailandensis). Cell counts of B. thailandensis were decreased ( P<0.05) as irradiation dose increased, and no differences ( P≥0.05) in cell counts of the bacteria were observed among different levels of NaCl and pH. D10 values ranged from 0.04 to 0.07 kGy, regardless of NaCl and pH level. These results indicate that low doses of gamma irradiation should be a useful treatment in decreasing the potential bioterrorism bacteria, which may possibly infect humans through foods.

Reaction mechanism of hydroxymaleimide induced by γ-irradiation in alcohol solvents

International Nuclear Information System (INIS)

Nakagawa, Seiko

2010-01-01

Methanol and 2-propanol solutions of hydroxymaleimide were irradiated with γ-ray and mechanism of its γ-irradiation-induced reactions was investigated through final-product analyses using high performance liquid chromatography (HPLC) coupled with mass spectroscopy. An addition reaction of a solvent radical toward hydroxymaleimide was dominant among its oxygen-free γ-irradiation-induced reactions in its alcohol solutions while it is known that electron attachment toward hydroxyphthalimide or hydroxysuccinimide is dominant among their γ-irradiation-induced reactions. The radical adduct abstracts hydrogen from solvent molecule to re-produce a solvent radical. Therefore, the degradation efficiency of hydroxymaleimide was more than ten times larger than that of hydroxyphthalimide and hydroxysuccinimide. Dimer was also produced through electron attachment process in the solutions of hydroxymaleimide. In addition, it was found that the degradation efficiency increased with decrease in dose rate. An additional reaction of a solvent radical toward hydroxymaleimide competes with a radical-radical recombination. The latter was reduced, with the former leading to efficient degradation of hydroxymaleimide increased by irradiation at lower dose rate. On the contrary, the production yield of the adduct radical as well as the degradation efficiency of hydroxymaleimide was inhibited in the presence of oxygen.

Reaction mechanism of hydroxymaleimide induced by γ-irradiation in alcohol solvents

International Nuclear Information System (INIS)

Nakagawa, Seiko

2010-01-01

Methanol and 2-propanol solutions of hydroxymaleimide were irradiated with γ-ray and mechanism of its γ-irradiation-induced reactions was investigated through final-product analyses using high performance liquid chromatography (HPLC) coupled with mass spectroscopy. An addition reaction of a solvent radical toward hydroxymaleimide was dominant among its oxygen-free γ-irradiation-induced reactions in its alcohol solutions while it is known that electron attachment toward hydroxyphthalimide or hydroxysuccinimide is dominant among their γ-irradiation-induced reactions. The radical adduct abstracts hydrogen from solvent molecule to re-produce a solvent radical. Therefore, the degradation efficiency of hydroxymaleimide was more than 10 times larger than that of hydroxyphthalimide and hydroxysuccinimide. Dimer was also produced through electron attachment process in the solutions of hydroxymaleimide. In addition, it was found that the degradation efficiency increased with decreasing the dose rate. An addition reaction of a solvent radical toward hydroxymaleimide competes with a radical-radical recombination. The latter was reduced and the former leading to efficient degradation of hydroxymaleimide increased by irradiation at lower dose rate. On the contrary, the production yield of the adduct radical as well as the degradation efficiency of hydroxymaleimide was inhibited in the presence of oxygen.

Roles of acid sphingomyelinase activation in neuronal cells apoptosis induced by microwave irradiation

International Nuclear Information System (INIS)

Zhang Lei; Xu Shangcheng; Zhang Guangbin; Yu Zhengping

2009-01-01

The present study is to examine the effect of microwave on acid sphingomyelinase (ASM) activity and expression, and to explore the role of ASM activation in neuronal cells apoptosis induced by microwave irradiation. Primary cultured hippocampal neurons were irradiated by 30 W/cm 2 microwave for 10 min, and ASM activity assay was used to investigate ASM activity alteration. RT-PCR and western blot were used to detect ASM mRNA and protein expression respectively. Apoptosis was observed by Hoechst 33342 fluorescence staining. ASM specific inhibitor imipramine was applied to inhibit ASM activation. It has been found that apoptosis rate of primary cultured hippocampal neurons increased significantly after microwave irradiation. ASM was activated while ASM mRNA and protein expression were upregulated in neurons after microwave irradiation. Pretreatment with imipramine could reverse neuronal apoptosis induced by microwave irradiation. Results show that microwave irradiation causes increment of ASM activation and expression and ASM activation is involved in microwave induced neuronal apoptosis. (authors)

Gamma Irradiation on Growth and Development of Amorphophallus muelleri Blume.

Directory of Open Access Journals (Sweden)

Edi Santosa

2014-09-01

Full Text Available ABSTRACT Iles-iles (Amorphophallus muelleri Blume produces apomictic seeds lead to low genetic variation. In order to induce genetic variation, germinated seeds were exposed to Gamma irradiation (Co-60 at doses of 10 to 100 Gy. Seed irradiation was conducted at Center for the Application of Isotope and Irradiation Technology -National Nuclear Energy Agency (CAIRT, Indonesia. Morphology and yield of M1 generation were observed. Results showed that irradiation at a dose of 10 Gy close to LD50 with survival rate 56%. Gamma irradiation at a dose of 10 Gy delayed seeds germination.  Germination rates gradually increased and reached maximum at 4 weeks after planting (WAP for control plants, and 14 WAP of irradiated plants. At 16 WAP, germination rate of 10 Gy irradiated plants was 56% and 84% for those of control plants. Irradiation induced chimera as indicated by short petiole, variegated and abnornal shape of leaflets. Some irradiated plants entered dormancy at 8-10 weeks later than control ones. Prolong vegetative periode lead the plants to produce heavier corms. This study revealed the possibility to induce variation of A. muelleri by using gamma irradition. Keywords: Amorphophallus muelleri, gamma irradiation (Co-60, morphological variation, mutation breeding

Renal effects of renal x irradiation and induced autoallergic glomerulonephritis

International Nuclear Information System (INIS)

Rappaport, D.S.; Casarett, G.W.

1979-01-01

This study was conducted to determine what influence a single large x-ray exposure of kidney has on the development and course of an experimental autoallergic glomerulonephritis (EAG) in rats. EAG was induced in female Sprague-Dawley rats by immunization with Bordetella pertussis vaccine and homogenate of homologous kidney tissue and Freund's complete adjuvant. Progressive arteriolonephrosclerosis (ANS) was observed in right (irradiated) kidneys following unilateral renal irradiation (1500 rad). Rats were either immunized, sham-immunized, irradiated, sham-irradiated, or both immunized and irradiated. Light and immunofluorescent microscopic observation, urine protein content, and kidney weights were evaluated. In immunized-irradiated animals the effects of irradiation and immunization were largely additive. Immunization did not considerably influence the development and course of ANS and irradiation did not considerably influence the development and course of EAG

Infrared A radiation promotes survival of human melanocytes carrying ultraviolet radiation-induced DNA damage.

Science.gov (United States)

Kimeswenger, Susanne; Schwarz, Agatha; Födinger, Dagmar; Müller, Susanne; Pehamberger, Hubert; Schwarz, Thomas; Jantschitsch, Christian

2016-06-01

The link between solar radiation and melanoma is still elusive. Although infrared radiation (IR) accounts for over 50% of terrestrial solar energy, its influence on human skin is not well explored. There is increasing evidence that IR influences the expression patterns of several molecules independently of heat. A previous in vivo study revealed that pretreatment with IR might promote the development of UVR-induced non-epithelial skin cancer and possibly of melanoma in mice. To expand on this, the aim of the present study was to evaluate the impact of IR on UVR-induced apoptosis and DNA repair in normal human epidermal melanocytes. The balance between these two effects is a key factor of malignant transformation. Human melanocytes were exposed to physiologic doses of IR and UVR. Compared to cells irradiated with UVR only, simultaneous exposure to IR significantly reduced the apoptotic rate. However, IR did not influence the repair of UVR-induced DNA damage. IR partly reversed the pro-apoptotic effects of UVR via modification of the expression and activity of proteins mainly of the extrinsic apoptotic pathway. In conclusion, IR enhances the survival of melanocytes carrying UVR-induced DNA damage and thereby might contribute to melanomagenesis. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effect of blood transfusions on canine renal allograft survival

International Nuclear Information System (INIS)

Van Der Linden, C.J.; Buurman, W.A.; Vegt, P.A.; Greep, J.M.; Jeekel, J.

1982-01-01

In this study significantly prolonged canine renal allograft survival has been demonstrated after transfusion of 100 ml of third-party whole blood given peroperatively. Peroperative transfusions of third-party leukocyte-free blood or pure lymphocyte cell suspensions did not influence graft survival. Futhermore, no improvement in graft survival has been found after a peroperative transfuson of irradiated whole blood (2500 rad). These data suggest that delayed graft rejection after blood transfusions can only be expected after the administration of whole blood. The role of competent lymphocytes in whole blood is questionable, since a transfusion of irradiated whole blood in combination with nonirradiated lymphocytes did not lead to prolonged graft survival. Immunosuppression of the recipient directly after transfusion seems to be essential to induce the beneficial effect of blood transfusions. This has been demonstrated for a transfusion of whole blood 14 days before transplantation. A single transfusion of 100 ml of whole blood 14 days before transplantation could effectively prolong graft survival if immunosuppression with azathioprine and prednisone was started on the day of transfusion. No improvement in graft survival has been found with such a transfusion if preoperative immunosuppression has been omitted

Effect of blood transfusions on canine renal allograft survival

International Nuclear Information System (INIS)

van der Linden, C.J.; Buurman, W.A.; Vegt, P.A.; Greep, J.M.; Jeekel, J.

1982-01-01

In this study significantly prolonged canine renal allograft survival has been demonstrated after transfusion of 100 ml of third-party whole blood given peroperatively. Peroperative transfusions of third-party leukocyte-free blood or pure lymphocyte cell suspensions did not influence graft survival. Furthermore, no improvement in graft survival has been found after a peroperative transfusion of irradiated whole blood (2500 rad). These data suggest that delayed graft rejection after blood transfusions can only be expected after the administration of whole blood. The role of competent lymphocytes in whole blood is questionable, since a transfusion or irradiated whole blood in combination with nonirradiated lymphocytes did not lead to prolonged graft survival. Immunosuppression of the recipient directly after transfusion seems to be essential to induce the beneficial effect of blood transfusions. This has been demonstrated for a transfusion of whole blood 14 days before transplantation. A single transfusion of 100 ml of whole blood 14 days before transplantation could effectively prolong graft survival if immunosuppression with azathioprine and prednisone was started on the day of transfusion. No improvement in graft survival has been found with such a transfusion if preoperative immunosuppression has been omitted

Structural changes and tribological performance of thermosetting polyimide induced by proton and electron irradiation

International Nuclear Information System (INIS)

Lv, Mei; Wang, Yanming; Wang, Qihua; Wang, Tingmei; Liang, Yongmin

2015-01-01

The structural changes and tribological performance of thermosetting polyimide were investigated by electron, proton or both combined irradiations at 25 keV in a ground-based simulation facility. Three forms of irradiations could lead to the formation of the carbonized layer on the polymer surface that could increase the hardness and adhesive force of the material. Proton irradiation induced more extensive changes in structure and friction behavior than electron irradiation by reason of the higher linear energy transfer value, and combined irradiation resulted in the largest impact, but which was less than the sum of the radiation effects of electron and proton. Moreover, the experimental results indicated that the changes in friction behavior are closely related with the carbonized layer, which was easily worn out in friction process and could introduce a shift from adhesion wear to three-body abrasive wear that reduced the wear rate and the friction coefficient. The friction process of irradiated samples could be divided into the initial stage and the steady stage. Three forms of irradiations all induced the high friction coefficient in the initial stage and the low friction coefficient in the steady stage, and the wear rate of the irradiated samples decreased in the order: electron irradiation>proton irradiation>combined irradiation. - Highlights: • Proton irradiation induced more extensive changes in structure and friction behavior than electron irradiation. • The effect of combined irradiation was less than that of the sum of electron and proton irradiation. • Three forms of irradiations all induced the high initial friction coefficient and the low steady-stage friction coefficient. • The initial friction stage means a fast-wearing adhesive process while the steady-state of the system is a three-body abrasion

Irradiation induced precipitation: a thermodynamical approach

International Nuclear Information System (INIS)

Bocquet, J.-L.; Martin, Georges.

1979-02-01

A binary alloy (A, B) under steady state irradiation is considered as a ternary alloy (A, B, defects) in constrained equilibrium (the constraint represented by the irradiation consists in maintaining a given supersaturation of point defects). All possible two-body interactions (attractive, repulsive) have been checked between the solvent A, the solute B, and the defects C. The conditions of an irradiation corresponds to a low point-defect concentration; the only cases of interest are those where such a low concentration makes new phases precipitate, which are richer in solute than the initial solid-solution. Radiation induced precipitation is expected to occur under the following necessary conditions: - when the binary alloy (A, B) shows ordering or is ideal, a necessary condition is that the binary solute-defects must show ordering. - when the binary alloy (A, B) shows clustering, a necessary condition is that the temperature must be close to the critical mixing temperature Tsub(AB)sup(D). The physical significance of these conditions is discussed [fr

Effects of insulin on the survival of irradiated chinese hamster lung cells

Energy Technology Data Exchange (ETDEWEB)

Lin, P S; Kwock, L; Hefter, K; Wallach, D F.H.; Brotman, R [Tufts-New England Medical Center, Boston, Mass. (USA)

1977-01-01

Insulin treatment (10/sup -7/-10/sup -9/ M) before ..gamma.. irradiation (50 to 500 rads) increases the long term survival of Chinese hamster lung cells (DON). Our data indicates that the radioprotective effect of insulin is not due to a modulation of cyclic-adenosine-3',5'-monophosphate levels within these cells. The results suggest that the radiosensitive plasma membrane component postulated to be involved in the interphase death of thymocytes and protected by insulin may have a counterpart in DON cells.

Structural and defects induced phenomena in γ-rays irradiated 6H-SiC

International Nuclear Information System (INIS)

Sibuyi, P.; Ngom, B.D.; Kotsedi, L.

2016-01-01

Damages and/or defects induced by γ-rays irradiation on 6H-SiC single crystals in channeled configuration towards 〈006〉/〈0012〉 crystallographic directions are reported in the range of 0–1200 kGy. Atomic force microscopy, X-rays diffraction, Raman and photoluminescence investigations were used to obtain a comprehensive set of informations on the nature and population distribution of the induced defects. Primarily, there was no carbon clusterization upon γ-rays irradiation and hence no formation of others SiC polytypes. In contrast, the γ-rays irradiation has induced an increase of the surface roughness at higher doses, which indicates a structural degradation. Larger doses induced an emergence of deeper shallow traps at energies greater than 350 meV below the bandgap. - Highlights: • No formation of others SiC polytypes. • The gamma rays irradiation has induced a slight surface amorphization. • A re-crystallization at lower and higher doses is noticed. • Larger doses induced a substantial internal stress.

Relaxation behavior and dose dependence of radiation induced radicals in irradiated mango

International Nuclear Information System (INIS)

Kameya, Hiromi; Kakita, Daisuke; Kaimori, Yoshihiko; Ukai, Mitsuko; Kikuchi, Masahiro; Kobayashi, Yasuhiko; Shimoyama, Yuhei

2010-01-01

Mangoes are imported to Japan after treated with hot water. Recently, irradiated mangoes imported to U. S. are widely used. This paper reports on the ESR method for analyzing the radiation induced radicals of irradiated mangoes. Upon the γ ray irradiation, a strong single peak in the flesh and skin of mangoes was observed at g=2.004. This singlet peak may be attributed to organic free radicals. The ESR spectra of the flesh and skin of mangoes showed the radiation induced radicals due to cellulose by irradiation over 12 kGy. The relaxation times (T 1 and T 2 ) of the singlet signal were calculated. T 2 showed dose response according to increasing the irradiation dose levels, while T 1 was almost constant. The value of (T 1 T 2 ) 1/2 showed the dependence of irradiation dose level. (author)

Evaluation of induced radioactivity in 10 MeV-electron irradiated spices, (1)

International Nuclear Information System (INIS)

Furuta, Masakazu; Katayama, Tadashi; Ito, Norio; Mizohata, Akira; Matsunami, Tadao; Shibata, Setsuko; Toratani, Hirokazu; Takeda, Atsuhiko.

1994-01-01

Black pepper, white pepper, red pepper, ginger and turmeric were irradiated with 10 MeV electrons from a linear accelerator to a dose of 100 kGy and radioactivity was measured in order to estimate induced radioactivity in the irradiated foods. Induced radioactivity could not be detected significantly by γ-ray spectrometry in the irradiated samples except for spiked samples which contain some photonuclear target nuclides in the list of photonuclear reactions which could produce radioactivity below 10 MeV. From the amount of observed radioactivities of short-lived photonuclear products in the spiked samples and calculation of H 50 according to ICRP Publication 30, it was concluded that the induced radioactivity and its biological effects in the 10 MeV electron-irradiated natural samples were negligible in comparison with natural radioactivity from 40 K contained in the samples. (author)

Analysis of irradiation processes for laser-induced periodic surface structures

NARCIS (Netherlands)

Eichstädt, J.; Huis In 't Veld, A.J.

2013-01-01

The influence of errors on the irradiation process for laser-induced periodic surface structures (LIPSS) was studied theoretically with energy density simulations. Therefore an irradiation model has been extended by a selection of technical variations. The influence of errors has been found in a

Effect of gamma irradiation on Burkholderia thailandensis (Burkholderia pseudomallei surrogate) survival under combinations of pH and NaCl

International Nuclear Information System (INIS)

Yoon, Yohan; Kim, Jae-Hun; Byun, Myung-Woo; Choi, Kyoung-Hee; Lee, Ju-Woon

2010-01-01

This study evaluated the effect of gamma irradiation on Burkholderia thailandensis (Burkholderia pseudomallei surrogate; potential bioterrorism agent) survival under different levels of NaCl and pH. B. thailandensis in Luria Bertani broth supplemented with NaCl (0-3%), and pH-adjusted to 4-7 was treated with gamma irradiation (0-0.5 kGy). Surviving cell counts of bacteria were then enumerated on tryptic soy agar. Data for the cell counts were also used to calculate D 10 values (the dose required to reduce 1 log CFU/mL of B. thailandensis). Cell counts of B. thailandensis were decreased (P 10 values ranged from 0.04 to 0.07 kGy, regardless of NaCl and pH level. These results indicate that low doses of gamma irradiation should be a useful treatment in decreasing the potential bioterrorism bacteria, which may possibly infect humans through foods.

Survival and reproductive capacity of the tobacco budworm, heliothis virescens (lepidoptera:noctuidae), irradiated as diapausing and young nondiapausing pupae

International Nuclear Information System (INIS)

Proshold, F.I.; North, D.T.

1978-01-01

Pupal survival, mating, and sperm transfer in tobacco budworm, Heliothis virescens (F.), irradiated as diapause pupae, decreased proportionately with increasing doses of 3, 5, and 7.5 krad. Also, the fertility of tobacco budworms irradiated as nondiapause pupae and of the F 1 progeny of such males decreased with increasing dose. When the female partner received eupyrene sperm, insects irradiated while the pupae were in diapause were fertile as were their progeny. Therefore, it does not appear plausible to irradiate diapause pupae of our strain of tobacco budworms to obtain sterile insects for a release program. (author)

The characteristics and mechanism of apoptosis induced by internal irradiation

International Nuclear Information System (INIS)

Hong Chengjiao; Zhang Junning; Zhu Shoupeng

2001-01-01

Apoptosis in tumor cells induced by radionuclides is likely the most effective way to cure cancer. In order to explore the possibility in clinic application, the characteristics and mechanism of apoptosis induced by internal irradiation were investigated. The apoptosis and expressions of bcl-2mRNA, bcl-2 and bax of K 562 cells following internal exposure with different accumulated absorbed doses of strontium-89 were studied. 6 h after irradiation, the characteristics of apoptosis and necrosis appeared in K 562 cells. The apoptosis and necrosis enhanced with the prolongation of internally contaminated time at 6 h, 9 h, 12 h, 24 h and 48 h. The expressions of bcl-2mRNA decreased at 12 h, most remarkably at 24 h. The expressions of bcl-2 decreased after irradiation whereas bax had no obvious changes. The results suggest that the apoptosis induced by internal exposure may be regulated by lower expressions of bcl-2mRNA and bcl-2, lower bcl-2/bax value

The irradiation induced creep of graphite under accelerated damage produced by boron doping

International Nuclear Information System (INIS)

Brocklehurst, J.E.

1975-01-01

The presence of boron enhances fast neutron irradiation damage in graphite by providing nucleation sites for interstitial loop formation. Doping with 11 B casues an increase in the irradiation induced macroscopic dimensional changes, which have been shown to result from an acceleration in the differential crystal growth rate for a given carbon atom displacement rate. Models of irradiation induced creep in graphite have centred around those in which creep is induced by internal stresses due to the anisotopic crystal growth, and those in which creep is activated by atomic displacements. A creep test on boron doped graphite has been performed in an attempt to establish which of these mechanisms is the determining factor. An isotropic nuclear graphite was doped to a 11 B concentration of 0.27 wt.%. The irradiation induced volume shrinkage rate at 750 0 C increased by a factor of 3 over that of the virgin graphite, in agreement with predictions from the earlier work, but the total creep strains were comparable in both doped and virgin samples. This observation supports the view that irradiation induced creep is dependent only on the carbon atom displacement rate and not on the internal stress level determined by the differential crystal growth rate. The implications of this result on the irradiation behaviour of graphite containing significant concentrations of boron are briefly discussed. (author)

Selection of thermal-resistant leavening (Saccharomyces boulardii) through gamma irradiation

International Nuclear Information System (INIS)

Neves, Maria Jose; Martins, Flaviano Santos

2000-01-01

Yeast cells acquire resistance to a several stress condition when they are previously exposed to a mild form of the same or of a different stress. In this way yeast cells exposure to temperatures higher than the optimum for growth results in a enhancement of the heat shock proteins and accumulation of trehalose. These cells then acquire the ability to survive under more extreme conditions, a phenomenon referred as transitory thermo-tolerance. We decided to test if gamma irradiation can induced a permanent thermo-tolerance in survival cells irradiated. Lyophilized cells of S. boulardii were irradiated with a 60 cobalt source. This cells were plated in solid medium. The survival cells were counted and the trehalose level were determined. In a second step, this survivals cells were incubated in liquid medium then submitted to a lethal heat shock (52 deg C, 15 min). The cells were plated and again grown at 30 deg C. The survival index and the level of trehalose were again determined. The procedure were repeated successively. The strains showed more thermo-resistance and the level of trehalose was increased without linear correlation with the number of viable cells. (author)

Erlotinib-induced rash spares previously irradiated skin

International Nuclear Information System (INIS)

Lips, Irene M.; Vonk, Ernest J.A.; Koster, Mariska E.Y.; Houwing, Ronald H.

2011-01-01

Erlotinib is an epidermal growth factor receptor inhibitor prescribed to patients with locally advanced or metastasized non-small cell lung carcinoma after failure of at least one earlier chemotherapy treatment. Approximately 75% of the patients treated with erlotinib develop acneiform skin rashes. A patient treated with erlotinib 3 months after finishing concomitant treatment with chemotherapy and radiotherapy for non-small cell lung cancer is presented. Unexpectedly, the part of the skin that had been included in his previously radiotherapy field was completely spared from the erlotinib-induced acneiform skin rash. The exact mechanism of erlotinib-induced rash sparing in previously irradiated skin is unclear. The underlying mechanism of this phenomenon needs to be explored further, because the number of patients being treated with a combination of both therapeutic modalities is increasing. The therapeutic effect of erlotinib in the area of the previously irradiated lesion should be assessed. (orig.)

Life prolongation and 5-year survival by intensive irradiation of inoperable lung cancer

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Eichhorn, H.-J.

1982-01-01

The effect of intensive radiotherapy on 1-5 year survival rates of patients with inoperable lung cancer is investigated. Some 123 cases were treated with 200 kV X-rays (> 3500 cGy tumour dose) and 1046 with cobalt-60 ν-rays (> 5000 cGy tumour dose). All patients had inoperable, histologically confirmed tumours, limited to one side of the thorax. Survival rates for 1 year were 22% and 37% respectively; for 3 years 1% and 5%; and for 5 years 0 and 2.5%. In all highly differentiated tumours the authors obtained a 5-year survival with telecobalt therapy of 6.5%, and for all oat-cell cases, 2.5%. By comparing the total result with their own control group of 'untreated', but prognostically more favourable patients (122 thoracotomized cases without resection) the increase of survival rates achieved by Cobalt-60 therapy is convincing (2.5 times for 1 year, 5 times for 2 years). Nevertheless, the very unfavourable prognosis for more than half of the cases justifies trials with systemic therapy. To date chemotherapy does not appear to influence survival times (except for small-cell tumours). Therefore randomized trials with two half-body irradiations (800 cGy each, 'Toronto method') are recommended. (Auth.)

Effect of Bifidobacterium breve B-3 on skin photoaging induced by chronic UV irradiation in mice.

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Satoh, T; Murata, M; Iwabuchi, N; Odamaki, T; Wakabayashi, H; Yamauchi, K; Abe, F; Xiao, J Z

2015-01-01

Probiotics have been shown to have a preventative effect on skin photoaging induced by short term UV irradiation, however, the underlying mechanisms and the effect of probiotics on skin photoaging induced by chronic UV irradiation remain unclear. In this study, we investigated the effect of Bifidobacterium breve B-3 on skin photoaging induced by chronic UV irradiation in hairless mice. Mice were irradiated with UVB three times weekly and orally administered B. breve B-3 (2×10(9) cfu/mouse /day) for 7 weeks. Nonirradiated mice and UVB-irradiated mice without probiotic treatment were used as controls. B. breve B-3 significantly suppressed the changes of transepidermal water loss, skin hydration, epidermal thickening and attenuated the damage to the tight junction structure and basement membrane induced by chronic UVB irradiation. Administration of B. breve B-3 tended to suppress the UV-induced interleukin-1β production in skin (P=0.09). These results suggest that B. breve B-3 could potentially be used to prevent photoaging induced by chronic UV irradiation.

The challenge in treating locally recurrent T3-4 nasopharyngeal carcinoma: the survival benefit and severe late toxicities of re-irradiation with intensity-modulated radiotherapy.

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Tian, Yun-Ming; Huang, Wei-Zeng; Yuan, Xia; Bai, Li; Zhao, Chong; Han, Fei

2017-06-27

Effective treatments for patients with advanced locally recurrent nasopharyngeal carcinoma (NPC) are limited. This investigation was to determine the potential benefits from re-irradiation by intensity-modulated radiotherapy (IMRT) on survival and the effects of severe late toxicities. A retrospective study was conducted in 245 patients diagnosed with locally recurrent T3-T4 NPC who had undergone re-irradiation with IMRT. Follow-up data was colletedand factors associated with survival and severe late toxicities were analyzed. The 5-year local-regional failure-free survival, distant failure-free survival and overall survival rates were 60.9%, 78.3% and 27.5%, respectively. The presence of severe late complications, recurrent T4 disease and gross tumor volume >30 cm3 were associated with poor survival. The incidences of mucosal necrosis, temporal lobe necrosis, cranial neuropathy and trismus were 22.0%, 14.6%, 27.0% and 14.6% respectively. Re-irradiation with IMRT is an effective choice in patients with locally recurrent T3-T4 NPC. However, the survival benefits can be partly offset by severe late complications and optimum treatments in these patients remain a challenge.

Elemental process of amorphization induced by electron irradiation in Si

International Nuclear Information System (INIS)

Yamasaki, Jun; Takeda, Seiji; Tsuda, Kenji

2002-01-01

We recently found that amorphization is induced in Si by electron irradiation. Examining the amorphization systematically, we have established the diagram of steady states under electron irradiation, either amorphous Si (a-Si) or crystalline Si (c-Si) as a function of incident electron energy, electron dose, and irradiation temperature. Utilizing transmission electron microscopy, electron energy filtered diffraction and electron energy-loss spectroscopy, we have characterized the atomic structure, the electronic structure, and the thermal stability of a-Si induced by electron irradiation. Based on the experimental data, we have also concluded that the amorphization is caused by the accumulation of not point defects but small cascade damages. Analyzing the change in the intensity of halo diffraction rings during amorphization, we have clarified that the smallest cascade damage that contributes to amorphization includes only about four Si atoms. This presumably supports the amorphization mechanism that four self-interstitial atoms form the quasistable structure I4 in c-Si and it becomes an amorphous embryo

Irradiation-induced mutation experiments with eiploid and tetraploid tomato plants

International Nuclear Information System (INIS)

Boda, J.

1979-01-01

Tomato mutation experiments are described. The tomatoes used in the experiment were the diploid Reziszta and its autotetraploid variety. The experimental plants were exposed to an irradiation of 5000 rsd for 1-2 days, and after transplantation into the gamma field, to chronic irradiation during the whole growing season. The chronic treatment heavily reduced fertility in the generations of tetraploid tomato plants. Recurrent treatment of tetraploid led to further deterioration in fertility. Several berries were formed with few seeds or with no seeds at all. After three irradiations, the chlorophyll mutation frequency increased in the diploid and tetraploid tomato plants. For diploids, treatment applied at the seedling stage gave a lower chlorophyll mutation frequency. With tetraploids the same treatment induced similar chlorophyll mutation frequency. As regards to phenotypic variability of quantitative characteristics in diploid and tetraploid tomatoes, the single and repeated chronic irradiation induced no increase in the variability of properties like flowering time, weight, height etc. (author)

Increased Epidermal Growth Factor Receptor (EGFR Associated with Hepatocyte Growth Factor (HGF and Symptom Severity in Children with Autism Spectrum Disorders (ASDs

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Anthony J. Russo

2014-01-01

Full Text Available Background One in 88 children in the US is thought to have one of the autism spectrum disorders (ASDs. ASDs are characterized by social impairments and communication problems. Growth factors and their receptors may play a role in the etiology of ASDs. Research has shown that epidermal growth factor receptor (EGFR activation is associated with nerve cell development and repair. This study was designed to measure plasma levels of EGFR in autistic children and correlate these levels with its ligand, epidermal growth factor, other related putative biomarkers such as hepatocyte growth factor (HGF, the ligand for MET (MNNG HOS transforming gene receptor, as well as the symptom severity of 19 different behavioral symptoms. Subjects and Methods Plasma EGFR concentration was measured in 33 autistic children and 34 age- and gender-similar neurotypical controls, using an enzyme-linked immunosorbent assay. Plasma EGFR levels were compared to putative biomarkers known to be associated with EGFR and MET and severity levels of 19 autism-related symptoms. Results We found plasma EGFR levels significantly higher in autistic children, when compared to neurotypical controls. EGFR levels correlated with HGF and high-mobility group protein B1 (HMGB1 levels, but not other tested putative biomarkers, and EGFR levels correlated significantly with severity of expressive language, conversational language, focus/attention, hyperactivity, eye contact, and sound sensitivity deficiencies. Conclusions These results suggest a relationship between increased plasma EGFR levels and designated symptom severity in autistic children. A strong correlation between plasma EGFR and HGF and HMGB1 suggests that increased EGFR levels may be associated with the HGF/Met signaling pathway, as well as inflammation.

Protection of Escherichia coli cells against the lethal effects of ultraviolet and X-irradiation by prior X-irradiation. A genetic and physiological study

Energy Technology Data Exchange (ETDEWEB)

Smith, K C; Martignoni, K D [Stanford Univ., Calif. (USA). Dept. of Radiology

1976-12-01

When log phase cells of wild-type E.coli K-12 were maintained in growth medium after X-irradiation, they became progressively more resistant to a subsequent exposure to UV or X-radiation. The time to achieve maximum resistance was about 60 min. The uvrB, uvrD, polA and certain exrA strains (W3110 background) also demonstrated this X-ray-induced resistance to subsequent UV or X-irradiation but recA, recB, lex (AB1157 or W3110 backgrounds) and other exrA strains (AB1157 background) did not. The resistance induced in wild-type, uvrB and uvrD cells was characterized by the production or enhancement of a shoulder on the survival curves obtained for the second irradiation, while the resistance induced in the W3110 exrA strains was expressed only as a change in slope. The induction of resistance in the W3110 exrA strain was not inhibited by the presence of chloramphenical, but that in the wild-type cells appeared to be. The production or enhancement of a shoulder on the survival curves of the rec/sup +/ lex/sup +/ exr/sup +/ cells is consistent with the concept of the radiation induction of repair enzymes. Alternative explanations, however, are discussed.

An ESR study of radicals induced in irradiated fresh mango

International Nuclear Information System (INIS)

Kikuchi, Masahiro; Hussain, Mohammed S.; Morishita, Norio; Kobayashi, Yasuhiko; Ukai, Mitsuko; Shimoyama, Yuhei

2009-01-01

An electron spin resonance (ESR) spectroscopic study was performed on the radicals induced irradiated fresh mangoes. Fresh Philippine mangoes were irradiated by the γ-rays, lyophilized and powdered. The ESR spectrum of the dry specimen showed a strong main peak at g=2.004 and a pair of peaks at both magnetic fields of the main peak. The main peak detected from flesh and skin specimens faded away in a few days after the irradiation. On the other hand, the side peaks showed a well-defined dose response even 9 days after the irradiation. The side-peak is a useful mean to define the irradiation on fresh mangoes. (author)

Irradiation-induced doping of Bismuth Telluride Bi2Te3

International Nuclear Information System (INIS)

Rischau, Carl Willem

2014-01-01

Bismuth Telluride Bi 2 Te 3 has attracted enormous attention because of its thermoelectric and topological insulator properties. Regarding its bulk band structure Bi 2 Te 3 is a band insulator with an energy gap of around 150-170 meV. However, the native anti-site defects that are present in real samples always dope this band insulator and shift the chemical potential into the valence or conduction band. In this PhD, the Fermi surface of as-grown and electron irradiated p-type Bi 2 Te 3 single crystals has been investigated extensively using electrical transport experiments. For moderate hole concentrations (p ∼< 5 x 10 18 cm -3 ), it is confirmed that electrical transport can be explained by a six-valley model and the presence of strong Zeeman-splitting. At high doping levels (p≅5 x 10 18 cm -3 ), the hole concentrations determined from Hall and Shubnikov-de Haas (SdH) effect differ significantly which is attributed to an impurity/defect band introduced by the anti-site defects. In this work, we show that it is possible to dope p-type Bi 2 Te 3 in a very controlled manner using electron-irradiation by performing detailed in- and ex-situ electrical transport studies on samples irradiated at room and at low temperatures with 2.5 MeV electrons. These studies show that the defects induced at both irradiation temperatures act as electron donors and can thus be used to convert the conduction from p- to n-type. The point of optimal compensation is accompanied by an increase of the low-temperature resistivity by several orders of magnitude. Irradiation at room temperature showed that both the p-type samples obtained after irradiation to intermediate doses as well as the samples in which the conduction has been converted to n-type by irradiation, still have a well defined Fermi surface as evidenced by SdH oscillations. By studying the Hall coefficient in-situ during low temperature electron irradiation, the coexistence of electron- and hole-type carriers was evidenced

γIrradiation induced formation of PCB-solvent adducts in aliphatic solvents

International Nuclear Information System (INIS)

Lepine, F.; Milot, S.; Gagne, N.

1990-01-01

γIrradiation induced formation of PCB-solvent adducts was investigated as a model for PCB residues in irradiated food. Formation of cyclohexyl adducts of PCBs was found to be significant when pure PCB congeners and Aroclor mixture were irradiated in cyclohexane and cyclohexene. Reaction pathways were investigated, and the effects of oxygen and electron scavenger were studied

Effect of irradiation on the temporomandibular joint in streptozotocin-induced diabetic rat

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Ahn, Ki Dong; Hwang, Eui Hwan; Lee, Sang Rae [Kyunghee University College of Medicine, Seoul (Korea, Republic of)

2004-06-15

To investigate the histopathological changes in the temporomandibular joint in streptozotocin-induced diabetic rat following irradiation. Sprague-Dawley rats weighing about 250 gm were divided into three groups: control, diabetic, and diabetic-irradiated groups. Diabetes mellitus was induced in the rats by injecting streptozotocin. Rats in the control group were injected with citrate buffer only. After 5 days, the head and neck region of the rats in diabetic-irradiated group were irradiated with single absorbed dose of 10 Gy. The rats were killed at 1, 3, 7, 14, 21, and 28 days after irradiation. The specimen including the temporomandibular joint were sectioned and observed using a histopathological method. In the diabetic group, severe bone resorption in the mandibular condyle was observed throughout the period of experiment. Necrosis of bone marrow and trabeculae was observed at 28 days after diabetic state. Atrophy and fibrosis in the retrodiscal tissue was gradually progressed during the time of the experiment. In the diabetic-irradiated group, severe bone resorption in the mandibular condyle was observed during the early experimental phases, but regeneration of bone marrow was initiated at 14 days after diabetic state and irradiation. Also, calcification of abnormal trabeculae was observed at 28 days after diabetic state and irradiation. The retrodiscal tissue was degenerated in the early experimental phases, but it had been gradually regenerated during the experimental time. This experiment suggests that bone resorption and degeneration in the mandibular condyle are caused by the induction of diabetes, and abnormal bone formation is induced after irradiation in diabetic state.

Effect of irradiation on the temporomandibular joint in streptozotocin-induced diabetic rat

International Nuclear Information System (INIS)

Ahn, Ki Dong; Hwang, Eui Hwan; Lee, Sang Rae

2004-01-01

To investigate the histopathological changes in the temporomandibular joint in streptozotocin-induced diabetic rat following irradiation. Sprague-Dawley rats weighing about 250 gm were divided into three groups: control, diabetic, and diabetic-irradiated groups. Diabetes mellitus was induced in the rats by injecting streptozotocin. Rats in the control group were injected with citrate buffer only. After 5 days, the head and neck region of the rats in diabetic-irradiated group were irradiated with single absorbed dose of 10 Gy. The rats were killed at 1, 3, 7, 14, 21, and 28 days after irradiation. The specimen including the temporomandibular joint were sectioned and observed using a histopathological method. In the diabetic group, severe bone resorption in the mandibular condyle was observed throughout the period of experiment. Necrosis of bone marrow and trabeculae was observed at 28 days after diabetic state. Atrophy and fibrosis in the retrodiscal tissue was gradually progressed during the time of the experiment. In the diabetic-irradiated group, severe bone resorption in the mandibular condyle was observed during the early experimental phases, but regeneration of bone marrow was initiated at 14 days after diabetic state and irradiation. Also, calcification of abnormal trabeculae was observed at 28 days after diabetic state and irradiation. The retrodiscal tissue was degenerated in the early experimental phases, but it had been gradually regenerated during the experimental time. This experiment suggests that bone resorption and degeneration in the mandibular condyle are caused by the induction of diabetes, and abnormal bone formation is induced after irradiation in diabetic state.

MASM, a Matrine Derivative, Offers Radioprotection by Modulating Lethal Total-Body Irradiation-Induced Multiple Signaling Pathways in Wistar Rats

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Jianzhong Li

2016-05-01

Full Text Available Matrine is an alkaloid extracted from Sophora flavescens Ait and has many biological activities, such as anti-inflammatory, antitumor, anti-fibrosis, and immunosuppressive properties. In our previous studies, the matrine derivative MASM was synthesized and exhibited potent inhibitory activity against liver fibrosis. In this study, we mainly investigated its protection against lethal total-body irradiation (TBI in rats. Administration of MASM reduced the radiation sickness characteristics and increased the 30-day survival of rats before or after lethal TBI. Ultrastructural observation illustrated that pretreatment of rats with MASM significantly attenuated the TBI-induced morphological changes in the different organs of irradiated rats. Gene expression profiles revealed that pretreatment with MASM had a dramatic effect on gene expression changes caused by TBI. Pretreatment with MASM prevented differential expression of 53% (765 genes of 1445 differentially expressed genes induced by TBI. Pathway enrichment analysis indicated that these genes were mainly involved in a total of 21 pathways, such as metabolic pathways, pathways in cancer, and mitogen-activated protein kinase (MAPK pathways. Our data indicated that pretreatment of rats with MASM modulated these pathways induced by TBI, suggesting that the pretreatment with MASM might provide the protective effects on lethal TBI mainly or partially through the modulation of these pathways, such as multiple MAPK pathways. Therefore, MASM has the potential to be used as an effective therapeutic or radioprotective agent to minimize irradiation damages and in combination with radiotherapy to improve the efficacy of cancer therapy.

UV survival of human mycoplasmas

International Nuclear Information System (INIS)

Aoki, Shigeji; Ito, Shoko; Watanabe, Takehiko

1979-01-01

The inactivation by ultraviolet (UV) light irradiation of mycoplasma cells of five human strains was monitored by investigating the colony-forming ability. The survival curves of five strains tested indicated that the cells of Mycoplasma buccale only are single and homogenously susceptible to UV light. The effect of the repair inhibitor, caffeine, on the colony-forming ability of UV-irradiated cells was investigated with M. buccale because of its homogeneous susceptibility to UV light. The colony formation of irradiated cells was markedly depressed by post-irradiation treatment with caffeine at concentration that had little or no effect on the colony formation of unirradiated cells. The colony-forming units (CFU) of UV-irradiated cells which were kept in broth without caffeine in the dark increased without a lag as the time in the dark increased. The colony-forming ability of the irradiated cells completely recovered after 3 hr in the dark. However, when irradiated cells were kept in the presence of caffeine, no increase in their CFU was observed. The mode of action of caffeine on UV-irradiated cells closely resembles that described for other organisms which possess dark reactivation systems for UV-induced damage in deoxyribonucleic acid. Thus, the results obtained provide evidence for the existence of a dark repair function in M. buccale. (author)

Effects of UV-B irradiation on growth, survival, pigmentation and nitrogen metabolism enzymes in Cyanobacteria

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Sinha, R.P.; Hader, D.P. [Institut fuer Botanik und Pharmazeutische Biologie, Friedrich-Alexander Universitaet, Erlangen (Germany); Kumar, H.D.; Kumar, A. [Banaras Hindu University, Varanasi (India)

1995-12-31

The effects of artificial UV-B irradiation on growth, survival, pigmentation, nitrate reductase (NR), glutamine synthetase (GS) and total protein profile have been studied in a number of N{sub 2}-fixing cyanobacterial strains isolated from rice (paddy) fields in India. Different organisms show different effects in terms of growth and survival. Complete killing of Anabaena sp. and Nostoc carmium occurs after 120 min of UV-B exposure, whereas the same occurs only after 150 min of exposure in the case of Nostoc commune and Scytonema sp. Growth patterns of the cells treated with UV-B revealed that Nostoc commune and Scytonema sp. are comparatively more tolerant than Anabaena sp. and Nostoc carmium. Pigment content, particularly phycocyanin, was severely decreased following UV-B irradiation in all strains tested so far. In vivo NR activity was found to increase, while in vivo GS activity was decreased following exposure to UV-B for different durations in all test organisms; although complete inhibition of GS activity did not occur even after 120 min of UV-B exposure. (author). 37 refs, 6 figs.

Effects of UV-B irradiation on growth, survival, pigmentation and nitrogen metabolism enzymes in Cyanobacteria

International Nuclear Information System (INIS)

Sinha, R.P.; Hader, D.P.; Kumar, H.D.; Kumar, A.

1995-01-01

The effects of artificial UV-B irradiation on growth, survival, pigmentation, nitrate reductase (NR), glutamine synthetase (GS) and total protein profile have been studied in a number of N 2 -fixing cyanobacterial strains isolated from rice (paddy) fields in India. Different organisms show different effects in terms of growth and survival. Complete killing of Anabaena sp. and Nostoc carmium occurs after 120 min of UV-B exposure, whereas the same occurs only after 150 min of exposure in the case of Nostoc commune and Scytonema sp. Growth patterns of the cells treated with UV-B revealed that Nostoc commune and Scytonema sp. are comparatively more tolerant than Anabaena sp. and Nostoc carmium. Pigment content, particularly phycocyanin, was severely decreased following UV-B irradiation in all strains tested so far. In vivo NR activity was found to increase, while in vivo GS activity was decreased following exposure to UV-B for different durations in all test organisms; although complete inhibition of GS activity did not occur even after 120 min of UV-B exposure. (author)

Influence of diethyl maleate in irradiated mice survival and related to percentages of serum proteins

International Nuclear Information System (INIS)

Bernardes, E.; Mastro, N.L. del

1990-01-01

The use of radiomodifying drugs that alter the radiation effect, protecting or sensitizing cells and organisms, presents great interest in tumor radiotherapy. Glutathione (GSH) can be described as the major endogenous radioprotector. The diethyl maleate (DEM) is a drug able to block intracellular GSH. This work aims at the establishment of the radiomodifying competence of DEM administered in two different vehicles, peanut oil and aqueous ethanolic solution by the analysis of mouse survival curves as well as the relative percentages of serum proteins. Groups of animals were previously injected intraperitoneally with 0.3 ml of 418 e 150 μM DEM respectively in each one of the vehicles one hour before irradiated with an 60 Co acute dose of 9 Gy. The survival of mice was followed during 30 days and electrophoretic profiles of serum proteins 1,3 and 7 days after irradiation. The results showed that the action of DEM om mouse radiosensitivity depends on the vehicles used, considering that both media showed a radio modifier action. (author)

Ovarian carcinoma: improved survival following abdominopelvic irradiation in patients with a completed pelvic operation

International Nuclear Information System (INIS)

Dembo, A.J.; Bush, R.S.; Beale, F.A.; Bean, H.A.; Pringle, J.F.; Sturgeon, J.; Reid, J.G.

1979-01-01

A prospective, stratified, randomized study of 190 postoperative ovarian carcinoma patients with Stages IB, II, and III (asymptomatic) presentations is reported. The median time of follow-up was 52 months. Patients in whom bilateral salpingo-oophorectomy and hysterectomy (BSOH) could not be completed because of extensive pelvic tumor had a poor prognosis which did not differ for any of the therapies tested. When BSOH was completed, pelvic plus abdominopelvic irradiation (P + AB) with no diaphragmatic shielding significantly improved patient survival rate and long-term control of occult upper abdominal disease in approximately 25% more patients than pelvic irradiation alone or followed by adjuvant daily chlorambucil therapy. The effectiveness of P + AB in BSOH-completed patients was independent of stage or tumor grade and was most clearly appreciated in patients with all gross tumor removed. Chlorambucil added to pelvic irradiation delayed the time to treatment failure without reducing the number of treatment failures

Prolonged bone marrow and skin allograft survival after pretransplant conditioning with cyclophosphamide and total lymphoid irradiation

International Nuclear Information System (INIS)

Kersey, J.H.; Kruger, J.; Song, C.; Kloster, B.

1980-01-01

Current studies were designed to provide long-term survival of allogeneic skin and bone marrow in mice preconditioned with various combinations of cyclophosphamide (CY) and/or total lymphoid irradiation (TLI). Long-term skin graft and bone marrow survival was obtained across the major histocompatibility barrier (BALB/c into C57BL/6) using pregrafting conditioning with either fractionated TLI or the combination of CY with a single dose of TLI. CY alone and a single dose of TLI alone were relatively ineffective as regrafting immunosuppressive combinations. Allogeneic bone marrow was required for long-term skin graft survival with either conditioning regimen. Allogeneic marrow transplantation resulted in somewhat more deaths than syngeneic transplantation with both CY + TLI and fractionated TLI

Clonogenic cell line survival of a human liver cancer cell line SMMC-7721 after carbon ion irradiation with different LET

International Nuclear Information System (INIS)

Lei Suwen; Su Xu; Wang Jifang; Li Wenjian

2003-01-01

Objective: To investigate the survival fraction of a human liver cancer cell line SMMC-7721 following irradiation with carbon ions with different LET. Methods: cells of the human liver cancer cell line SMMC-7721 were irradiated with carbon ions (LET=30 and 70 keV/μm). The survival fraction was determined with clonogenic assay after 9 days incubation in a 5% CO 2 incubator at 37 degree C. Results: When the survival fractions of 70 keV/μm were D s = 0.1 and D s=0.01 absorption dose were 2.94 and 5.88 Gy respectively, and those of 30 keV/μm were 4.00 and 8.00 Gy respectively. Conclusion: For the SMMC-7721 cell line, 70 keV/μm is more effective for cell killing than 30 keV/μm

DNA repair in gamma-and UV-irradiated Escherichia coli treated with caffeine and acriflavine

International Nuclear Information System (INIS)

Zhestyanikov, V.D.; Savel'eva, G.E.

1978-01-01

A study is made of the postradiation effect of caffeine and acriflavine on the survival rate and DNA repair in E. coli exposed to γ- and UV-radiation. When added to postradiation growth medium caffeine and acriflavine lower the survival rate of γ-irradiated radioresistant strains, B/r and Bsub(s-1)γR, and UV-irradiated UV-resistant strain B/r, and do not appreciably influence the survival of strains that are sensitive to γ- and UV-radiation. The survival rate of UV-irradiated mutant BsUb(s-1) somewhat increases in the presence of caffeine. Caffeine and acriflavine inhibit repair of single-stranded DNA breaks induced in strain B/r by γ-radiation (slow repair) and UV light. Acriflavine arrests a recombination branch of postreplication repair of DNA in E. coli Bsub(s-1)γR Whereas caffeine does not influence this process

Expression and migratory analysis of 5 human uveal melanoma cell lines for CXCL12, CXCL8, CXCL1, and HGF

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Di Cesare Sebastian

2007-01-01

Full Text Available Abstract Background The aim of this study was to characterize the presence and roles of CXCL12, CXCL8, CXCL1, and HGF in five human uveal melanoma cell lines, using different methods, in order to ascertain their significance in this disease. Methods Five human uveal melanoma cell lines (92.1, SP6.5, MKT-BR, OCM-1, and UW-1 of known proliferative, invasive, and metastatic potential were used in this experiment. A migration assay was used in order to assess the responsiveness of each cell line towards the four chosen chemotactic factors. Immunohistochemistry was then performed for all five cell lines (cytospins using antibodies directed toward CXCL1, CXCL8 and their receptors CXCR2 and CXCR1 respectively. Quantitative real-time PCR was then performed on all five cell lines in order to establish the presence of these four chemotactic factors. Results All five human uveal melanoma cell lines migrated towards the four chosen chemotactic factors at a level greater than that of the negative control. Chemokines CXCL1 and CXCL8 resulted in the greatest number of migrating cells in all five of our cell lines. Immunohistochemistry confirmed the expression of CXCL1, CXCL8, and their receptors CXCR2 and CXCR1 in all five of the cell lines. Quantitative real-time PCR results established expression of CXCL8, CXCL1, and HGF in all 5 cell lines tested. CXCL1 and CXCL8 are highly expressed in SP6.5 and UW-1. None of the five cell lines expressed any detectable levels of CXCL12. Conclusion The migratory ability of the 5 human uveal melanoma cell lines was positively influenced by the four chemotactic factors tested, namely CXCL12, CXCL8, CXCL1, and HGF. Self-expression of chemotactic factors CXCL8, CXCL1, and HGF may indicate an autocrine system, which perhaps contributes to the cells' metastatic ability in vivo.

Study of HeLa cells clone survival after X-ray irradiation in the presence of cisplatin

Science.gov (United States)

Baulin, A. A.; Sukhikh, E. S.; Vasilyev, S. A.; Sukhikh, L. G.; Sheino, I. N.

2017-09-01

Radiation therapy in the presence of heavy elements nuclei (Z > 53) is widely developed these days. The presence of such nuclei in cancer cells results in the local increase of energy release from primary photon beam thus increasing relative biological efficiency. In this paper we present the preliminary results of the cell survival study while irradiating cells by X-Ray photon beam in the presence of cisplatin (Pt, Z = 78). The preliminary results show the decrease of the cell survival in the presence of both radiation and cisplatin.

Cryptoendolithic Antarctic Black Fungus Cryomyces antarcticus Irradiated with Accelerated Helium Ions: Survival and Metabolic Activity, DNA and Ultrastructural Damage

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Claudia Pacelli

2017-10-01

Full Text Available Space represents an extremely harmful environment for life and survival of terrestrial organisms. In the last decades, a considerable deal of attention was paid to characterize the effects of spaceflight relevant radiation on various model organisms. The aim of this study was to test the survival capacity of the cryptoendolithic black fungus Cryomyces antarcticus CCFEE 515 to space relevant radiation, to outline its endurance to space conditions. In the frame of an international radiation campaign, dried fungal colonies were irradiated with accelerated Helium ion (150 MeV/n, LET 2.2 keV/μm, up to a final dose of 1,000 Gy, as one of the space-relevant ionizing radiation. Results showed that the fungus maintained high survival and metabolic activity with no detectable DNA and ultrastructural damage, even after the highest dose irradiation. These data give clues on the resistance of life toward space ionizing radiation in general and on the resistance and responses of eukaryotic cells in particular.

Apoptosis of nasopharyngeal carcinoma cell line (CNE-2) induced by neutron irradiation

International Nuclear Information System (INIS)

Liang Ke; He Shaoqin; Feng Yan; Tang Jinhua; Feng Qinfu; Shen Yu; Yin Weibo; Xu Guozhen; Liu Xinfan; Wang Luhua; Gao Li

1999-01-01

Objective: To study the apoptotic response of the nasopharyngeal carcinoma cell line (CNE-2) induced by neutron irradiation. Methods: CNE-2 cells were cultured as usual. Using the techniques of DNA agarose gel electrophoresis and DNA special fluorescent staining, the status of apoptosis in CNE-2 cells after neutron irradiation was detected. Results: It was shown that the apoptosis can be induced in CNE-2 cell after neutron radiation. Six hrs, after different doses of neutron (0/0.667/1.333/2.000/2.667/3.333 Gy) and X-ray 0/2/4/6/8/10 Gy) irradiation the apoptotic rates were 2.4%, 6.3%, 7.1%, 9.5%, 13.5%, 14.6% and 2.4%, 3.8%, 5.7%, 7.8%, 10.4%, 11.7%, respectively; at 48 hrs they were 18.3%, 21.5%, 22.8%, 29.3%, 34.2% and 13.7%, 17.6%, 21.3%, 25.6%, 28.9%, respectively. At 10 hrs after neutron irradiation the DNA ladder of apoptosis could be detected between 0.667-3.333 Gy doses in CNE-2 cells by DNA agarose gel electrophoresis. Conclusion: Neutron radiation can induce apoptosis in tumor cells. Compared with the X-ray, neutron induces apoptosis in larger extent than X-ray in the same condition; meanwhile, apoptosis after irradiation is dose and time dependent

Renal effects of renal x irradiation and induced autoallergic glomerulonephritis

International Nuclear Information System (INIS)

Rappaport, D.S.

1977-01-01

This study was conducted to determine what, if any, influence a single large x-ray exposure of kidney has on the development and course of an experimental autoallergic glomerulonephritis (EAG) in rats. The EAG was induced by immunization with B. pertussis vaccine and homogenate of homologous kidney tissue and Freund's complete adjuvant. Rats were either immunized, sham-immunized, irradiated (1500 R to right kidney temporarily exteriorized), sham-irradiated, or both immunized and irradiated. Immunized-irradiated animals were irradiated either 4 or 2 weeks prior to, concurrently with, or 1 or 2 weeks after immunization, and were sacrificed at 2, 4, 6, 10, or 14 weeks post-immunization. Immunized-only and sham-immunized-only animals were sacrificed at corresponding post-immunization times, and irradiated-only and sham-irradiated-only animals were sacrificed at corresponding post-irradiation times. Progressive arteriolonephrosclerosis (ANA) was observed in right (irradiated) kidneys following x irradiation. The experimental autoallergic glomerulonephritis (EAG) was observed in both kidneys following immunization. The histopathological changes associated with EAG were distinct from those associated with ANS

Assessment of the Survival of Dental Implants in Irradiated Jaws Following Treatment of Oral Cancer: A Retrospective Study

Science.gov (United States)

Rana, Meenakshi Chauhan; Solanki, Swati; Pujari, Sudarshan C; Shaw, Eisha; Sharma, Swati; Anand, Abhishek; Singh, Harkanwal Preet

2016-01-01

Background: In patients undergoing head and neck surgery for various pathologic conditions, implants are one of the best restorative options and are increasing widely used. Therefore, we evaluated the success of dental implants in the irradiated jaws of patients following treatment of oral cancer oral cancer treated patients. Materials and Methods: Data of oral cancer treated patients was collected retrospectively from 2002 to 2008. We took 46 oral cancer treated patients in which implants were placed in irradiated jaws for rehabilitation. Results: It was found that out of 162 dental implants placed, 52 failed. Furthermore, there was no variation in the implant survival rate in between both the jaws. Radiation dose of <50 Gy units also showed significantly increased amount of implant survival rate. Conclusions: Implant survival is multifactorial and depends upon a number of factors like level of radiation exposure in that area, time gap between last radiation doses etc., Further research is required in this field to improve the esthetics and quality of life of cancer treated patients. PMID:27843270

Assessment of the survival of dental implants in irradiated jaws following treatment of oral cancer: A retrospective study

Directory of Open Access Journals (Sweden)

Meenakshi Chauhan Rana

2016-01-01

Full Text Available Background: In patients undergoing head and neck surgery for various pathologic conditions, implants are one of the best restorative options and are increasing widely used. Therefore, we evaluated the success of dental implants in the irradiated jaws of patients following treatment of oral cancer oral cancer treated patients. Materials and Methods: Data of oral cancer treated patients was collected retrospectively from 2002 to 2008. We took 46 oral cancer treated patients in which implants were placed in irradiated jaws for rehabilitation. Results: It was found that out of 162 dental implants placed, 52 failed. Furthermore, there was no variation in the implant survival rate in between both the jaws. Radiation dose of <50 Gy units also showed significantly increased amount of implant survival rate. Conclusions: Implant survival is multifactorial and depends upon a number of factors like level of radiation exposure in that area, time gap between last radiation doses etc., Further research is required in this field to improve the esthetics and quality of life of cancer treated patients.

A history of study on safety of irradiated foods (3). Induced radioactivity in irradiated foods

International Nuclear Information System (INIS)

Miyahara, Makoto

2006-01-01

Food irradiation can induce a small amount of radioactivity in the foods. The principal mechanisms of the nuclear reactions are (n, γ), (γ, n), (γ, γ'). The resulting nuclear products were found in irradiated foods were Na-24, P-32, Ca-45, C-11, N-13, and O-15 in the food irradiated by 24 MeV electron beam. The total radioactivity is less than 1/1000 of those of K-40 in the case of electron beams below 10 MeV or X rays below 5 MeV. Package materials affected neutron flux in the foods and enhanced the radioactivity. Electron beam machine produces neutrons and increases the flux in food. IAEA recommend to reduce neutron production in the facility. The safety of irradiated food in the radioactivity field still needs more progress. (author)

Ion irradiation-induced precipitation of Cr23C6 at dislocation loops in austenitic steel

International Nuclear Information System (INIS)

Jin, Shuoxue; Guo, Liping; Luo, Fengfeng; Yao, Zhongwen; Ma, Shuli; Tang, Rui

2013-01-01

The irradiation-induced precipitates in argon ion-irradiated austenitic stainless steel at 550 °C were examined via transmission electron microscopy. The selected-area electron diffraction patterns of precipitates indicated unambiguously that the precipitates were Cr 23 C 6 carbides. It was observed directly for the first time that irradiation-induced Cr 23 C 6 precipitates formed at dislocation loops in austenitic stainless steel, and coarsened with increasing irradiation dose.

Gamma ray irradiation to roots of tea-plants and induced mutant system

International Nuclear Information System (INIS)

Takeda, Yoshiyuki; Nekaku, Koji; Wada, Mitsumasa

1990-01-01

In order to utilize the useful mutation which is induced by irradiation for the breeding of tea-plants, the gamma-ray irradiation to the roots of tea-plants was carried out. The samples were the roots of tea-plants of four varieties dug up in February, 1984, and were adjusted to about 20 cm, then, put in the cold storage at 5degC for 9 months till the time of irradiation in November, 1984. However, a part of them was taken out in August, and planted in a field for 76 days to germinate, thereafter, used as the samples. The gamma-ray from a Co-60 source was irradiated in the radiation breeding laboratory of Agriculture Bioresources Research Institute at the total dose of 1, 2 and 3 kR and the dose rate of 500 R/h. The irradiated roots were planted as they are or in the state of being cut, and the rate of germination, the number of buds and the induced mutation were examined. Clear difference was not observed in the rate of germination and the number of buds between the irradiated samples and those without irradiation. The long roots were superior to the short roots regarding these items. The types of the induced mutation were mostly thin leaves, and also yellowing, mottling, fascination and so on occurred. The mutant system lacking trichomes on the back of new leaves is considered to be strong against tea anthracnose, and is valuable. (K.I.)

Gamma ray irradiation to roots of tea-plants and induced mutant system

Energy Technology Data Exchange (ETDEWEB)

Takeda, Yoshiyuki; Nekaku, Koji; Wada, Mitsumasa (National Research Inst. of Vegetables, Ornamental Plants and Tea, Ano, Mie (Japan))

1990-11-01

In order to utilize the useful mutation which is induced by irradiation for the breeding of tea-plants, the gamma-ray irradiation to the roots of tea-plants was carried out. The samples were the roots of tea-plants of four varieties dug up in February, 1984, and were adjusted to about 20 cm, then, put in the cold storage at 5degC for 9 months till the time of irradiation in November, 1984. However, a part of them was taken out in August, and planted in a field for 76 days to germinate, thereafter, used as the samples. The gamma-ray from a Co-60 source was irradiated in the radiation breeding laboratory of Agriculture Bioresources Research Institute at the total dose of 1, 2 and 3 kR and the dose rate of 500 R/h. The irradiated roots were planted as they are or in the state of being cut, and the rate of germination, the number of buds and the induced mutation were examined. Clear difference was not observed in the rate of germination and the number of buds between the irradiated samples and those without irradiation. The long roots were superior to the short roots regarding these items. The types of the induced mutation were mostly thin leaves, and also yellowing, mottling, fascination and so on occurred. The mutant system lacking trichomes on the back of new leaves is considered to be strong against tea anthracnose, and is valuable. (K.I.).

Cell death induced by gamma irradiation of developing skeletal muscle

International Nuclear Information System (INIS)

Olive, M.; Blanco, R.; Rivera, R.; Cinos, C.; Ferrer, I.

1995-01-01

Newborn Sprague-Dawley rats were exposed to a single dose of 2 Gy gamma rays and killed from 6 h to 5 d later. Increased numbers of dying cells, characterised by their extreme chromatin condensation and often nuclear fragmentation were seen in skeletal muscle 6 h after irradiation. Dying cells decreased to nearly normal values 48 h later. In situ labelling of nuclear DNA fragmentation identified individual cells bearing fragmented DNA. The effects of gamma rays were suppressed following cycloheximide i.p. at a dose of 1 μg/g body weight given at the time of irradiation. Taken together, the present morphological and pharmacological results suggest that gamma ray induced cell death in skeletal muscle is apoptotic, and that the process is associated with protein synthesis. Finally, proliferating cell nuclear antigen-immunoreactive cells, which were abundant in control rats, decreased in number 48 h after irradiation. However, a marked increase significantly above normal age values was observed at the 5th day, thus suggesting that regeneration occurs following irradiation-induced cell death in developing muscle. (author)

Influence of Magnolol on the bystander effect induced by alpha-particle irradiation

Energy Technology Data Exchange (ETDEWEB)

Wong, T.P.W.; Law, Y.L. [Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong); Tse, A.K.W.; Fong, W.F. [Research and Development Division, School of Chinese Medicine, Hong Kong Baptist University, Baptist University Road, Kowloon Tong (Hong Kong); Yu, K.N. [Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong)], E-mail: peter.yu@cityu.edu.hk

2010-04-15

In this work, the influence of Magnolol on the bystander effect in alpha-particle irradiated Chinese hamster ovary (CHO) cells was examined. The bystander effect was studied through medium transfer experiments. Cytokinesis-block micronucleus (CBMN) assay was performed to quantify the chromosome damage induced by alpha-particle irradiation. Our results showed that the alpha-particle induced micronuclei (MN) frequencies were suppressed with the presence of Magnolol.

Evidence for induced radioresistance from survival and other end points: An introduction

International Nuclear Information System (INIS)

Joiner, M.C.

1994-01-01

A substantial body of data published during the past 30 years makes a strong case for the existence of cellular radioprotective mechanisms that can be up-regulated in response to exposure to small doses of ionizing radiation. Either these open-quotes inducedclose quotes mechanisms can protect against a subsequent exposure to radiation that may be substantially larger than the initial open-quotes primingclose quotes or open-quotes conditioningclose quotes dose, or they may influence the shape of the survival response to single doses so that small radiation exposures are more effective per unit dose than larger exposures above a threshold where the induced radioprotection is triggered. Evidence for these effects comes from studies in vitro with protozoa, algae, higher plant cells, insect cells, mammalian and human cells, and studies on animal models in vivo. Work at the molecular level is now confirming that changes in levels of some cytoplasmic and nuclear proteins, and the increased expression of some genes, may occur within a few hours or even minutes of irradiation. This would be sufficiently quick to explain the phenomenon of induced radioresistance although the precise mechanism, whether by repair, cell cycle control or some other process, remains yet undefined. 35 refs

Insulin-Like Growth Factor 1 Mitigates Hematopoietic Toxicity After Lethal Total Body Irradiation

Energy Technology Data Exchange (ETDEWEB)

Zhou, Dunhua; Deoliveira, Divino; Kang, Yubin; Choi, Seung S. [Department of Medicine, Duke University Medical Center, Durham, North Carolina (United States); Li, Zhiguo [Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina (United States); Chao, Nelson J. [Department of Medicine, Duke University Medical Center, Durham, North Carolina (United States); Department of Pathology, Duke University Medical Center, Durham, North Carolina (United States); Department of Immunology, Duke University Medical Center, Durham, North Carolina (United States); Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina (United States); Chen, Benny J., E-mail: chen0032@mc.duke.edu [Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina (United States); Department of Medicine, Duke University Medical Center, Durham, North Carolina (United States)

2013-03-15

Purpose: To investigate whether and how insulin-like growth factor 1 (IGF-1) mitigates hematopoietic toxicity after total body irradiation. Methods and Materials: BALB/c mice were irradiated with a lethal dose of radiation (7.5 Gy) and treated with IGF-1 at a dose of 100 μg/dose intravenously once a day for 5 consecutive days starting within 1 hour after exposure. Survival and hematopoietic recovery were monitored. The mechanisms by which IGF-1 promotes hematopoietic recovery were also studied by use of an in vitro culture system. Results: IGF-1 protected 8 of 20 mice (40%) from lethal irradiation, whereas only 2 of 20 mice (10%) in the saline control group survived for more than 100 days after irradiation. A single dose of IGF-1 (500 μg) was as effective as daily dosing for 5 days. Positive effects were noted even when the initiation of treatment was delayed as long as 6 hours after irradiation. In comparison with the saline control group, treatment with IGF-1 significantly accelerated the recovery of both platelets and red blood cells in peripheral blood, total cell numbers, hematopoietic stem cells, and progenitor cells in the bone marrow when measured at day 14 after irradiation. IGF-1 protected both hematopoietic stem cells and progenitor cells from radiation-induced apoptosis and cell death. In addition, IGF-1 was able to facilitate the proliferation and differentiation of nonirradiated and irradiated hematopoietic progenitor cells. Conclusions: IGF-1 mitigates radiation-induced hematopoietic toxicity through protecting hematopoietic stem cells and progenitor cells from apoptosis and enhancing proliferation and differentiation of the surviving hematopoietic progenitor cells.

Insulin-Like Growth Factor 1 Mitigates Hematopoietic Toxicity After Lethal Total Body Irradiation

International Nuclear Information System (INIS)

Zhou, Dunhua; Deoliveira, Divino; Kang, Yubin; Choi, Seung S.; Li, Zhiguo; Chao, Nelson J.; Chen, Benny J.

2013-01-01

Purpose: To investigate whether and how insulin-like growth factor 1 (IGF-1) mitigates hematopoietic toxicity after total body irradiation. Methods and Materials: BALB/c mice were irradiated with a lethal dose of radiation (7.5 Gy) and treated with IGF-1 at a dose of 100 μg/dose intravenously once a day for 5 consecutive days starting within 1 hour after exposure. Survival and hematopoietic recovery were monitored. The mechanisms by which IGF-1 promotes hematopoietic recovery were also studied by use of an in vitro culture system. Results: IGF-1 protected 8 of 20 mice (40%) from lethal irradiation, whereas only 2 of 20 mice (10%) in the saline control group survived for more than 100 days after irradiation. A single dose of IGF-1 (500 μg) was as effective as daily dosing for 5 days. Positive effects were noted even when the initiation of treatment was delayed as long as 6 hours after irradiation. In comparison with the saline control group, treatment with IGF-1 significantly accelerated the recovery of both platelets and red blood cells in peripheral blood, total cell numbers, hematopoietic stem cells, and progenitor cells in the bone marrow when measured at day 14 after irradiation. IGF-1 protected both hematopoietic stem cells and progenitor cells from radiation-induced apoptosis and cell death. In addition, IGF-1 was able to facilitate the proliferation and differentiation of nonirradiated and irradiated hematopoietic progenitor cells. Conclusions: IGF-1 mitigates radiation-induced hematopoietic toxicity through protecting hematopoietic stem cells and progenitor cells from apoptosis and enhancing proliferation and differentiation of the surviving hematopoietic progenitor cells

Time-effect relationship of immunological adaptive response induced by low dose X-irradiation in mice

International Nuclear Information System (INIS)

Zhao Yong; Gong Shouliang; Liu Shuzheng

1995-01-01

Kunming mice irradiated with whole-body X-rays were used to observe time-effect relationship of immunological adaptive response induced by ionizing radiation. The results showed that pre-irradiation dose of 75 mGy X-rays with the intervals of 6-48 h between pre-irradiation and challenge irradiation could induce immunological adaptive response in the spontaneous proliferation of thymocytes and the responses of splenocytes to Con A and LPS in mice at 18-24 h after challenge irradiation with 1.5-2.0 Gy X-rays

Effect of ultraviolet-B-irradiated donor-specific blood transfusions and peritransplant immunosuppression with cyclosporine on rat cardiac allograft survival

International Nuclear Information System (INIS)

Oluwole, S.F.; Lau, H.T.; Reemtsma, K.; Hardy, M.A.

1988-01-01

We have previously demonstrated that pretreatment of ACI recipients with ultraviolet-irradiated donor-specific blood transfusion (UV-DST) leads to permanent cardiac allograft survival without further host immunosuppression (ACI rats are weak responders to Lewis lymphocytes in mixed-lymphocyte reaction). This study examines the effect of UV-DST and the timing of transfusions on ACI cardiac allograft survival in Lewis recipients with and without the addition of peritransplant cyclosporine (CsA) (20 mg/kg i.m.) given on days 0, +1, and +2 in relation to the time of transplantation. The mean survival time (MST) of ACI cardiac allografts in Lewis recipients was significantly increased to 33.6 +/- 5.7 days (P less than 0.001) by CsA treatment alone as compared to 6.5 +/- 0.5 days survival in control. When DST was given on day -3 combined with CsA, graft survival was increased to 42.0 +/- 9.3 days (P less than 0.01), as compared to 5.8 +/- 1.3 days when DST alone was used. When DST was irradiated with ultraviolet B (UV-DST) and administered on day -3 combined with peritransplant CsA, the MST was increased to 68.83 +/- 16.1 days as compared to an MST of 10.0 +/- 1.0 days in controls treated with UV-DST alone. When UV-DST was given on day -7 and combined with peritransplant CsA immunosuppression, the results were similar. However, when UV-DST was peritransplant CsA course, 4 of 6 recipients maintained their ACI heart allografts indefinitely (greater than 300 days) in contrast to the effect of UV-DST alone (MST of 13.5 days). Third-party (W/F) UV-irradiated blood transfusions were ineffective in prolonging ACI cardiac allografts in Lewis rats, regardless of whether the transfusions were given alone or in combination with peritransplant immunosuppression with CsA

UV light-induced survival response in a highly radiation-resistant isolate of the Moraxella-acinetobacter group

International Nuclear Information System (INIS)

Keller, L.C.; Thompson, T.L.; Maxcy, R.B.

1982-01-01

A highly radiation-resistant member of the Moraxella-Acinetobacter group, isolate 4, obtained from meat, was studied to determine the effect of preexposure to UV radiation on subsequent UV light resistance. Cultures that were preexposed to UV light and incubated for a short time in plate count broth exhibited increased survival of a UV light challenge dose. This response was inhibited in the presence of chloramphenicol. Frequencies of mutation to streptomycin, trimethoprim, and sulfanilamide resistance remained the same after the induction of this survival response and were not altered by treatment with mutagens, with the exception of mutation to streptomycin resistance after γ-irradiation or nitrosoguanidine or methyl methane sulfonate treatment. The results indicated that isolate 4 has a UV light-inducible UV light resistance mechanism which is not associated with increased mutagenesis. The characteristics of the radiation resistance response in this organism are similar to those of certain other common food contaminants. Therefore, considered as part of the total microflora of meat, isolate 4 and the other radiation-resistant Moraxella-Acinetobacter isolates should not pose unique problems in a proposed radappertizaton process

Blood vessel endothelium-directed tumor cell streaming in breast tumors requires the HGF/C-Met signaling pathway.

Science.gov (United States)

Leung, E; Xue, A; Wang, Y; Rougerie, P; Sharma, V P; Eddy, R; Cox, D; Condeelis, J

2017-05-11

During metastasis to distant sites, tumor cells migrate to blood vessels. In vivo, breast tumor cells utilize a specialized mode of migration known as streaming, where a linear assembly of tumor cells migrate directionally towards blood vessels on fibronectin-collagen I-containing extracellular matrix (ECM) fibers in response to chemotactic signals. We have successfully reconstructed tumor cell streaming in vitro by co-plating tumors cells, macrophages and endothelial cells on 2.5 μm thick ECM-coated micro-patterned substrates. We found that tumor cells and macrophages, when plated together on the micro-patterned substrates, do not demonstrate sustained directional migration in only one direction (sustained directionality) but show random bi-directional walking. Sustained directionality of tumor cells as seen in vivo was established in vitro when beads coated with human umbilical vein endothelial cells were placed at one end of the micro-patterned 'ECM fibers' within the assay. We demonstrated that these endothelial cells supply the hepatocyte growth factor (HGF) required for the chemotactic gradient responsible for sustained directionality. Using this in vitro reconstituted streaming system, we found that directional streaming is dependent on, and most effectively blocked, by inhibiting the HGF/C-Met signaling pathway between endothelial cells and tumor cells. Key observations made with the in vitro reconstituted system implicating C-Met signaling were confirmed in vivo in mammary tumors using the in vivo invasion assay and intravital multiphoton imaging of tumor cell streaming. These results establish HGF/C-Met as a central organizing signal in blood vessel-directed tumor cell migration in vivo and highlight a promising role for C-Met inhibitors in blocking tumor cell streaming and metastasis in vivo, and for use in human trials.

Computer modelling of radiation-induced bystander effect

International Nuclear Information System (INIS)

Khvostunov, Igor K.; Nikjoo, Hooshang

2002-01-01

Radiation-induced genomic instability and bystander effects are now well established consequences of exposure of living cells to ionising radiation. It has been observed that cells not directly hit by radiation tracks may still exhibit radiation effects. We present a quantitative modelling of the radiation-induced bystander effect based on a diffusion model of spreading the bystander signal. The model assumes the bystander factor to be a protein of low molecular weight, given out by the hit cell, diffusing in the medium and reacting with non-hit cells. The model calculations successfully predict the results of cell survival in an irradiated conditioned medium. The model predicts the shape of dose-effect relationship for cell survival and oncogenic transformation induced by broad-beam and micro-beam irradiation by alpha-particles. (author)

Modification of bacterial cell survival by postirradiation hypoxia

Energy Technology Data Exchange (ETDEWEB)

Vexler, F B; Eidus, L Kh

1986-01-27

It is shown that postirradiation hypoxia affects the survival of E.coli. Hypoxic conditions immediately after a single-dose irradiation diminish cell survival in nutrient medium. Increasing time intervals between irradiation and hypoxia decrease the efficiency of the latter, while 1 h after irradiation hypoxia does not modify the survival of irradiated cells. These findings reveal that the mechanisms of action of postirradiation hypoxia on eu- and prokaryotic cells are similar.

SHI induced irradiation effect on Mo/Si interface

International Nuclear Information System (INIS)

Agarwal, Garima; Agarwal, Shivani; Jain, Rajkumar; Lal, Chhagan; Jain, I.P.; Kabiraj, D.; Pandey, Akhilesh

2006-01-01

Present parametric study investigates the characteristics of SHI induced mixed molybdenum silicide film with various ion fluences. The deposition of molybdenum thin films onto the Silicon substrate was performed using e-beam evaporation, while the heavy Au ion irradiation with energy 120 MeV was subsequently applied to form molybdenum silicide. The samples have been characterized by grazing incidence X-ray diffraction (GIXRD) for the identification of phase formation at the interface. Formation of t-Mo 5 Si 3 mixed molybdenum silicide was observed on increasing the ion irradiation fluences. (author)

Irradiation-induced patterning in dilute Cu–Fe alloys

International Nuclear Information System (INIS)

Stumphy, B.; Chee, S.W.; Vo, N.Q.; Averback, R.S.; Bellon, P.; Ghafari, M.

2014-01-01

Compositional patterning in dilute Cu 1−x Fe x (x ≈ 12%) induced by 1.8 MeV Kr + irradiation was studied as a function of temperature using atom probe tomography. Irradiation near room temperature led to homogenization of the sample, whereas irradiation at 300 °C and above led to precipitation and macroscopic coarsening. Between these two temperatures the irradiated alloys formed steady state patterns of composition where precipitates grew to a fixed size. The size in this regime increased somewhat with temperature. It was also observed that the steady state concentrations of Fe in Cu matrix and Cu in the Fe precipitates both greatly exceeded their equilibrium solubilities, with the degree of supersaturation in each phase decreasing with increasing temperature. In the macroscopic coarsening regime, the Fe-rich precipitates showed indications of a “cherry-pit” structure, with Cu precipitates forming within the Fe precipitates. In the patterning regime, interfaces between Fe-rich precipitates and the Cu-rich matrix were irregular and diffuse

Study on apoptosis of prostate cancer cell induced by 125I seed irradiation

International Nuclear Information System (INIS)

Liao Anyan; Wang Junjie; Wang Jidong; Zhuang Hongqing; Zhao Yong

2007-01-01

Objective: To explore the mechanism of apoptosis induced by 125 I seed irradiation on PC3 cells. Methods: Human prostate cancer cell line PC3 was treated by irradiation of 125 I (2.77 cGy/h) with various dose. Agarose gel electrophoresis of DNA and flows cytometry were used to detect the apoptosis of PC3 cells and indirect immunofluorescence assay was used to detect the expression of Bcl-2. The activity of Caspase-3 was measured by Caspase Colorimetric Assay Kits. Results: Apoptosis of PC3 cells could be efficiently induced by 125 I seed irradiation. The apoptotic peaks were found by flow cytometry and DNA ladder appeared on 1.8% agarose gel. The activity of Caspase-3 on PC3 cells treated by 125 I seed irradiation was not changed significantly. Bcl-2 gene expression was down-regulated with the sample concentration increased. Conclusion: 125 I irradiation can induce the apoptosis of PC3 cells and the mechanism of apoptosis is related with down regulation of Bcl-2 gene expression and is not related with Caspase-3 activity. (authors)

Electron irradiation induced nanocrystal formation in Cu-borosilicate glass

Energy Technology Data Exchange (ETDEWEB)

Sabri, Mohammed Mohammed; Möbus, Günter, E-mail: g.moebus@sheffield.ac.uk [University of Sheffield, Department of Materials Science and Engineering (United Kingdom)

2016-03-15

Nanoscale writing of Cu nanoparticles in glasses is introduced using focused electron irradiation by transmission electron microscopy. Two types of copper borosilicate glasses, one with high and another with low Cu loading, have been tested at energies of 200–300 keV, and formation of Cu nanoparticles in a variety of shapes and sizes using different irradiation conditions is achieved. Electron energy loss spectroscopy analysis, combined with high-resolution transmission electron microscopy imaging, confirmed the irradiation-induced precipitated nanoparticles as metallic, while furnace annealing of the glass triggered dendrite-shaped particles of copper oxide. Unusual patterns of nanoparticle rings and chains under focused electron beam irradiation are also presented. Conclusively, electron beam patterning of Cu-loaded glasses is a promising alternative route to well-established femtosecond laser photoreduction of Cu ions in glass.

Cell-kinetics of the human uterine cervical carcinoma cells during radium irradiation

International Nuclear Information System (INIS)

Iwata, Masaharu; Sasaki, Hiroshi

1983-01-01

HeLa cells grown in a monolayer culture and in nude mice were exposed to graded dose rates (37, 55 or 200 rad/hour) and doses (500-2,000 rad) of radiation and analyzed in terms of their cell cycle distribution using flow-microfluorometry. In the case of the cultured HeLa cells, dose-survival curves were constructed using colony formation as the end-point. The HeLa cells, both in vitro and in vivo, accumulated in G2-M phases after both acute and chronic irradiation. The dose rate of 37 rad/hour proved to be the most effective in producing G2-M accumulation, which is the sensitive phase of the cell cycle. In comparing the G2-M accumulation to the irradiation time, 55 and 37 rad/hour proved to be similarly efficient in producing G2-M accumulation, both in vitro and in vivo. When survival of HeLa cells in vitro was studied, the radiation-induced changes in cell distribution correlated with cell survival and accounted for the change in the dose rate effect above 1,000 rads. In the case of in vivo HeLa cells, the decrease in the number of G0+G1 stage cells was demonstrated during chronic irradiation (37 and 55 rad/hour). The two low dose rates were equally efficient in producing a decrease in the number of G0+G1 cells. These data indicate that chronic irradiation induces redistribution and recruitment more effectively than acute irradiation. (author)

The effects of the first two rises of adrenal gland activity on survival of rats after whole-body irradiation

International Nuclear Information System (INIS)

Coffigny, Herve; Pasquier, Christian.

1980-04-01

Lethal irradiation of rats results in two rises of adrenal gland activity around the 3rd hour and the 3rd day following exposure respectively. The effects of each rise on survival of rats were studied during either reaction, 1) by inhibition of corticosterone synthesis by metopirone 2) by corticosterone injection to adrenalectomized rats. The first rise seemed deleterious to survival, whereas the second one was without effect. The specificity of adrenal reaction following exposure might explain the significance of the succession of other stresses for survival in the particular case of combined stresses [fr

Heavy ion induced mutation in arabidopsis

Energy Technology Data Exchange (ETDEWEB)

Tano, Shigemitsu [Japan Atomic Energy Research Inst., Takasaki, Gunma (Japan). Takasaki Radiation Chemistry Research Establishment

1997-03-01

Heavy ions, He, C, Ar and Ne were irradiated to the seeds of Arabidopsis thaliana for inducing the new mutants. In the irradiated generation (M{sub 1}), germination and survival rate were observed to estimate the relative biological effectiveness in relation to the LET including the inactivation cross section. Mutation frequencies were compared by using three kinds of genetic loci after irradiation with C ions and electrons. Several interesting new mutants were selected in the selfed progenies of heavy ion irradiated seeds. (author)

Beam-induced temperature changes in HVEM irradiations

International Nuclear Information System (INIS)

Garner, F.A.; Thomas, L.E.; Gelles, D.S.

1975-01-01

The peak value of the temperature distribution induced by energy loss of 1.0 MeV electrons in traversing a typical HVEM irradiation specimen can be very substantial. The origin and various features of this distribution were analyzed for a variety of specimen geometries. The major parametric dependencies are shown to be relatively independent of specimen geometry, however, and allow the definition of a scaling relationship that can be employed to predict temperature rises in materials that cannot be measured directly. The use of this scaling relationship requires that the experimenter minimize perturbations of the heat flow due to proximity of the central hole in the specimen. An experimental method of determining directly the magnitude and distribution of beam-induced temperature profiles was developed which utilizes the order-disorder transformation in Fe 3 Al and Cu 3 Au. Scaling of experimentally determined temperature changes leads to more realistic estimates of the total temperature rise than are currently available in various literature tabulations. The factors which determine the optimum selection of irradiation parameters for a given experiment are also discussed

Fatigue behavior of Type 316 stainless steel following neutron irradiation inducing helium

International Nuclear Information System (INIS)

Grossbeck, M.L.; Liu, K.C.

1980-01-01

Since a tokamak reactor operates in a cyclic mode, thermal stresses will result in fatigue in structural components, especially in the first wall and blanket. There has been limited work on fatigue in irradiated alloys but none on irradiated materials containing significant amounts of irradiation-induced helium. To provide scoping data and to study the effects of irradiation on fatigue behavior, 20%-cold-worked type 316 stainless steel from the MFE reference heat was studied

Gastroprotective effect of kefir on ulcer induced in irradiated rats.

Science.gov (United States)

Fahmy, Hanan A; Ismail, Amel F M

2015-03-01

The current study was designed to investigate the protective effect of kefir milk on ethanol-induced gastric ulcers in γ-irradiated rats. The results of the present study revealed that treatment with γ-irradiation and/or ethanol showed a significant increase in ulcers number, total acidity, peptic, H(+)K(+)ATPase, MMP-2 and MMP-9 activities and MDA level, which were accompanied by a significant decrease in the mucus content, the stomach GSH level, the GSH-Px activity and DNA damage. Pre-treatment with kefir milk exert significant improvement in all the tested parameters. Kefir milk exerts comparable effect to that of the antiulcer drug ranitidine. In conclusion, the present study revealed that oral administration of kefir milk prevents ethanol-induced gastric ulcer in γ-irradiated rats that could attribute to its antioxidant, anti-apoptotic and radio-protective activities. Copyright © 2015 Elsevier B.V. All rights reserved.

Inhibition of human colorectal adenocarcinoma cells with AdCMV-p53 gene transfection induced by irradiation

International Nuclear Information System (INIS)

Liu Bing; Min Fengling; Xie Yi; Zhou Qingming; Duan Xin; Chinese Academy of Sciences, Beijing; Zhang Hong; Li Wenjian; Hao Jifang; Zhou Guangming; Gao Qingxiang

2006-01-01

The effect of AdCMV-p53 gene transfection induced by γ-ray irradiation on human colorectal adenocarcinoma cells was investigated. The HT-29 cells were irradiated by 0.5, 1.0, 2.0 Gy 60 Co γ-rays, then were transfected with AdCMV-GFP (a replication of deficient recombinant adenoviral vector containing a CMV promoter and green fluorescent protein) or AdCMV-p53 (a replication of deficient recombinant adenoviral vector containing a CMV promoter and carrying human wild p53 gene). Cytotoxity was measured by clonogenic survival assay; apoptosis and the p53 expression were determined by flow cytometry. The results show that the pre-exposure of 0.5 Gy 60 Co γ-rays significantly enhanced the inhibition of HT-29 cells with AdCMV-53 transfection and promoted cell apoptosis. The inhibition rates for the groups of pre-exposure with 0.5 Gy and transfection with 40 and 80 MOI AdCMV-p53 were 50% and 20% higher than those for the groups of the mere transfection, and 40% more than the mere irradiation group. In the case of higher than 0.5 Gy pre-exposure, no significant difference was found between the pre-exposure with transfection group and the mere irradiation group. So 0.5 Gy pre-irradiation and AdCMV-p53 transfection obviously increases the inhibition of HT-29 cells with AdCMV-p53 transfection. The optimum condition is the lower than 1.0 Gy pre-exposure combined with the lower than 80 MOI AdCMV-p53 transfection. (authors)

Evaluation of Chemical Changes in Some Soybean Mutants Induced by Gamma Irradiation

International Nuclear Information System (INIS)

Abd-Elkalik, K.; Mekkawy, S.H.; El-Demerdash, H.M.

2010-01-01

The Egyptian soybean cultivar Giza-22 was used to induce genetic variability by using gamma rays at dose levels of 100, 150 and 200 Gy. Sixteen mutants (including parental cultivar) were evaluated in M3 generation for their agronomic traits and chemical analysis was done in seeds of M3 generation. Four mutants A21 (150 Gy), A22, A23 and A24 (200 Gy) showed superiority in their agronomic traits compared with parental cultivar. The results of chemical analysis of seeds of M3 generation showed that, oil and energy contents were unaffected by irradiation treatments while protein contents were significantly increased at doses 150 and 200 Gy. Phenolic and tannin contents in seeds of M3 generation showed no significant changes in their percentages due to irradiation treatments. Gamma irradiation significantly increased in linoleic acid content in most of the mutants compared with the control (Giza-22), whereas, there were decreases in linolenic acid content. Investigation of amino acid composition of mutants of M3 generation revealed significant increases in the essential amino acids in most mutants induced by gamma irradiation at 150 and 200 Gy. It could be suggested that the use of gamma irradiation can induce an improvement of the oil and protein composition in soybean

The impact of irradiation induced specimen charging on microanalysis in a scanning electron microscope

International Nuclear Information System (INIS)

Stevens-Kalceff, M.A.

2003-01-01

Full text: It is necessary to assess and characterize the perturbing influences of experimental probes on the specimens under investigation. The significant influence of electron beam irradiation on poorly conducting materials has been assessed by a combination of specialized analytical scanning electron and scanning probe microscopy techniques including Cathodoluminescence Microanalysis and Kelvin Probe Microscopy. These techniques enable the defect structure and the residual charging of materials to be characterized at high spatial resolution. Cathodoluminescence is the non-incandescent emission of light resulting from the electron irradiation. CL microscopy and spectroscopy in a Scanning Electron Microscope (SEM) enables high spatial resolution and high sensitivity detection of defects in poorly conducting materials. Local variations in the distribution of defects can be non-destructively characterized with high spatial (lateral and depth) resolution by adjusting electron beam parameters to select the specimen micro-volume of interest. Kelvin Probe Microscopy (KPM) is a Scanning Probe Microscopy technique in which long-range Coulomb forces between a conductive atomic force probe and the specimen enable the surface potential to be characterized with high spatial resolution. A combination of Kelvin Probe Microscopy (KPM) and Cathodoluminescence (CL) microanalysis has been used to characterize ultra pure silicon dioxide exposed to electron irradiation in a Scanning Electron Microscope. Silicon dioxide is an excellent model specimen with which to investigate charging induced effects. It is a very poor electrical conductor, homogeneous and electron irradiation produces easily identifiable surface modification which enables irradiated regions to be easily and unambiguously located. A conductive grounded coating is typically applied to poorly conducting specimens prior to investigation in an SEM to prevent deflection of the electron beam and surface charging, however

Cerenkov light and the production of photoreactivatable damage in X-irradiated E. coli

International Nuclear Information System (INIS)

Redpath, J.L.; Zabilansky, E.; Morgan, T.; Ward, J.F.

1981-01-01

Survival curve data for oxygenated E. coli AB2480 irradiated with 6 MVp photons in the absence and presence of DNA are presented for bacteria which have or have not received photoreactivation treatment following x-ray exposure. At the concentration of DNA used (OD = 4.4 at 260 nm) partial protection against induction of photoreactivatable damage was attained. Following photoreactivation the survival curves had the same slope, irrespective of the presence or absence of DNA. Survival data for oxygenated E.coli AB2480 irradiated with 50 Gy of 6 MVp photons in the presence of DNA at varying concentrations (OD range 0.5 to 12) and then processed with or without exposure to photoreactivating light are also presented. Survival increased with DNA concentration in the absence, but not in the presence, of photoreactivation. It is concluded that theoretical considerations and experimental data are consistent with Cerenkov light being responsible for the production of a major part of the photoreactivatable damage induced in E.coli DNA by high energy X-,γ- or electron irradiation, but that the data obtained with low energy X-rays (300 kVp) and with high energy X-rays (6 MVp) plus DNA as a 'scavenger' of Cerenkov light, are indicative of a component of the photoreactivatable damage being induced by a mechanism not involving Cerenkov light. (U.K.)

Cerenkov light and the production of photoreactivatable damage in X-irradiated E. coli

Energy Technology Data Exchange (ETDEWEB)

Redpath, J L; Zabilansky, E; Morgan, T [California Univ., Irvine (USA). Dept. of Radiological Sciences; Ward, J F [California Univ., San Diego, La Jolla (USA). Dept. of Radiology

1981-05-01

Survival curve data for oxygenated E. coli AB2480 irradiated with 6 MVp photons in the absence and presence of DNA are presented for bacteria which have or have not received photoreactivation treatment following x-ray exposure. At the concentration of DNA used (OD = 4.4 at 260 nm) partial protection against induction of photoreactivatable damage was attained. Following photoreactivation the survival curves had the same slope, irrespective of the presence or absence of DNA. Survival data for oxygenated E.coli AB2480 irradiated with 50 Gy of 6 MVp photons in the presence of DNA at varying concentrations (OD range 0.5 to 12) and then processed with or without exposure to photoreactivating light are also presented. Survival increased with DNA concentration in the absence, but not in the presence, of photoreactivation. It is concluded that theoretical considerations and experimental data are consistent with Cerenkov light being responsible for the production of a major part of the photoreactivatable damage induced in E. coli DNA by high energy X-, ..gamma..- or electron irradiation, but that the data obtained with low energy X-rays (300 kVp) and with high energy X-rays (6 MVp) plus DNA as a scavenger of Cerenkov light, are indicative of a component of the photoreactivatable damage being induced by a mechanism not involving Cerenkov light.

Microfluidic wound-healing assay to assess the regenerative effect of HGF on wounded alveolar epithelium.

OpenAIRE

Felder Marcel; Sallin Pauline; Barbe Laurent; Haenni Beat; Gazdhar Amiq; Geiser Thomas; Guenat Olivier

2012-01-01

We present a microfluidic epithelial wound healing assay that allows characterization of the effect of hepatocyte growth factor (HGF) on the regeneration of alveolar epithelium using a flow focusing technique to create a regular wound in the epithelial monolayer. The phenotype of the epithelial cell was characterized using immunostaining for tight junction (TJ) proteins and transmission electron micrographs (TEMs) of cells cultured in the microfluidic system a technique that is reported here ...

Study on radiation regulation of hypoxia inducible factor-1α expression and its correlation with hepatoma radiosensitivity

International Nuclear Information System (INIS)

Jin Wensen; Kong Zhaolu; Shen Zhifen; Tong Shungao; Ji Huajun; Jin Yizun

2008-01-01

Objective: To study the regulation of hypoxia inducible factor-1α (HIF-1α) expression in hepatoma cells after irradiation and the expression of HIF-1α effect on the radiosensitivity of heptoma cells. Methods: HepG2 cells were pretreated by Cobalt chloride (COCl 2 ), a chemical hypoxia agent, to induce and stabilize the expression of HIF-1α, and then exposed to different γ-irradiation doses. Clonogenic assay was used to evaluate HepG2 cell survival fraction (SF) after irradiation under normoxia and chemical hypoxia. Reverse transcriptase polymerase chain reaction (RT-PCR) and immunoblot assay (Western blot) were utilized to detect the changes of intracellular HIF-1α on the level of transcripation and translation. Results: Cell survival level was elevated by chemical hypoxia and there was a statistical difference between chemical hypoxic group and normoxic group. The ratios of SF(SF co /SF o 2 )on two different conditions were increased with irradiation doses. Meanwhile, the irradiation induced up-regulation of HIF-1α in dose-dependent manner. The expression of HIF-1α was correlated with HepG2 cell survival level to some extent. Conclusions: Irradiation could up-regulate the level of HIF-1α expression in HepG2 cells under chemical hypoxic condition. The cells survival level might be influenced by the changes in HIF-1α expression. (authors)

Caffeine-induced hematological changes after whole-body irradiation in rat

Energy Technology Data Exchange (ETDEWEB)

Kim, Jin Kyu [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of); Kim, Ji Hyang; Yoon Yong Dal [Hanyang University, Seoul (Korea, Republic of)

2004-07-01

Recent research indicated dietary antioxidants were useful radioprotectors to protect organisms against radiation-induced tissue lethality and other deleterious effects. Radioprotective effects of vitamin C have been demonstrated in certain cells and animals, which would result from scavenging free radicals. Moreover, the previous studies indicated that caffeine had been shown to potently act the radioprotector in irradiated mice. However it is not clear exactly about effects of caffeine treatments chronically after irradiation. So the present studies were designed to identify the hematological effect of caffeine treatments chronically one month after whole-body gamma irradiation.

The LDsub(50/30) and the survival time in whole-body gamma-irradiated conventional and germfree Minnesota miniature piglets

International Nuclear Information System (INIS)