WorldWideScience

Sample records for rad53 determining radioresistance

  1. Interactions of checkpoint-genes RAD9, RAD17, RAD24 and RAD53 determining radioresistance of Yeast Saccharomyces Cerevisiae

    International Nuclear Information System (INIS)

    Koltovaya, N.A.; Nikulushkina, Yu.V.; Roshchina, M.P.; Devin, A.B.

    2007-01-01

    The mechanisms of genetic control of progress through the division cell cycle (checkpoint-control) in yeast Saccharomyces cerevisiae have been studied intensively. To investigate the role of checkpoint-genes RAD9, RAD17, RAD24, RAD53 in cell radioresistance we have investigated cell sensitivity of double mutants to γ-ray. Double mutants involving various combinations with rad9Δ show epistatic interactions, i.e. the sensitivity of the double mutants to γ-ray was no greater than that of more sensitive of the two single mutants. This suggests that all these genes govern the same pathway. This group of genes was named RAD9-epistasis group. It is interesting to note that the genes RAD9 and RAD53 have positive effect but RAD17 and RAD24 have negative effect on radiosensitivity of yeast cells. Interactions between mutations may differ depending on the agent γ-ray or UV-light, for example mutations rad9Δ and rad24Δ show additive effect for γ-ray and epistatic effect for UV-light

  2. RAD9, RAD17; RAD24, and RAD53 control one pathway of resistance to γ irradiation in Saccharomyces cerevisiae

    International Nuclear Information System (INIS)

    Koltovaya, N.A.; Nikulushkina, Yu.V.; Roshina, M.P.; Devin, A.B.

    2009-01-01

    Mechanisms for the genetic control of the cell cycle transition (checkpoint control) have been studied in more detail in yeast Saccharomyces cerevisiae. To clarify tho role of the RAD9, RAD17, RAD24, and RAD53 checkpoint genes in cell radioresistance, diploid double mutants were analyzed for cell sensitivity to ionizing radiation. All mutations in combination with rad9Δ were shown to manifest the epistatic type of interaction. Our results suggest that the RAD9, RAD17, RAD24, and RAD53 checkpoint genes belong to a single epistasis group called the RAD9 group and participate in the same pathway. RAD9 and RAD53 have a positive effect on sensitivity to γ irradiation, whereas RAD17 and RAD24 have a negative effect. For haploid interactions between mutations may differ in the case of γ or UV irradiation, mutations - for example, rad9Δ and rad24Δ - were shown to have an additive effect in the first case and epistatic - in the second. The analyzed genes can also participate in minor mechanisms of radioresistance that are relatively independent of the above major mechanism

  3. Checkpoint Kinase Rad53 Couples Leading- and Lagging-Strand DNA Synthesis under Replication Stress.

    Science.gov (United States)

    Gan, Haiyun; Yu, Chuanhe; Devbhandari, Sujan; Sharma, Sushma; Han, Junhong; Chabes, Andrei; Remus, Dirk; Zhang, Zhiguo

    2017-10-19

    The checkpoint kinase Rad53 is activated during replication stress to prevent fork collapse, an essential but poorly understood process. Here we show that Rad53 couples leading- and lagging-strand synthesis under replication stress. In rad53-1 cells stressed by dNTP depletion, the replicative DNA helicase, MCM, and the leading-strand DNA polymerase, Pol ε, move beyond the site of DNA synthesis, likely unwinding template DNA. Remarkably, DNA synthesis progresses further along the lagging strand than the leading strand, resulting in the exposure of long stretches of single-stranded leading-strand template. The asymmetric DNA synthesis in rad53-1 cells is suppressed by elevated levels of dNTPs in vivo, and the activity of Pol ε is compromised more than lagging-strand polymerase Pol δ at low dNTP concentrations in vitro. Therefore, we propose that Rad53 prevents the generation of excessive ssDNA under replication stress by coordinating DNA unwinding with synthesis of both strands. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. A Rad53 Independent Function of Rad9 Becomes Crucial for Genome Maintenance in the Absence of the RecQ Helicase Sgs1

    DEFF Research Database (Denmark)

    Nielsen, Ida; Bentsen, Iben Bach; Andersen, Anni Hangaard

    2013-01-01

    becomes crucial for genome maintenance in the absence of Sgs1. Despite this, our dissection of the MMS checkpoint response reveals parallel, but unequal pathways for Rad53 activation and highlights significant differences between MMS- and hydroxyurea (HU)-induced checkpoint responses with relation...

  5. Role of endogeneous thiols in the determination of radio-resistance of E. coli B culture in different phases of its growth

    Energy Technology Data Exchange (ETDEWEB)

    Konstantinova, M M [AN SSSR, Moscow. Inst. Biologii Razvitiya

    1975-05-01

    An investigation was made of the link between the radioresistance of various stages of development of a culture of E. coli B with the level of sulfhydryl groups in the cells at each stage. The analysis was carried out by comparing the content of sulfhydryl groups in the cells, with their viability after irradiation and by determining the effectiveness of radio-protective and radio-sensitizing agents on a culture of various ages. It was shown that the thiols are the factor that determines the variation in radiosensitivity of a culture of E. coli B in the logarithmic and stationary phases of growth.

  6. Characterization of the radioresistance in the radioresistant bacterium deinococcus radiodurans

    International Nuclear Information System (INIS)

    Kong Xiangrong; Du Zeji

    1999-01-01

    The radioresistance of wild type Deinococcus radiodurans KD8301 and the factors affecting the radioresistance were investigated. KH3111 which was a DNA repair mutant of KD8301 (Zeji Du, 1998) was used to be compared with KD8301. Deinococcus radiodurans was discovered by Anderson et al (1956) in X-ray sterilized canned meat that was found to have undergone spoilage. this bacterium and other species of this genus share extreme resistance to ionizing radiation and other agents that damage DNA. Wild type KD8301 and its sensitive mutant KH3111 were irradiated with 60 Co γ-ray at the dose range 0.5 ∼ 10 kGy. Dose-survival fraction curves were made and the radio resistances were determined by LD 99 . The relative contents of DNA in cells were measured by Fluorescence Spectrophotometry (Freedman and Bruce, 1971). The results indicated that wild type KD8301 possesses more radioresistant than its mutant KH3111, LD99 were 9.5 kGy and 2.4 kGy respectively. KD8301 grown at exponential phase showed a decreased resistance to radiation, and the LD99 was 5.1 kGy. No differences of DNA/protein in cells were found between the exponential phase and the stationary phase. The results could be concluded that wild type KD8301 possesses remarkable radioresistance, but this ability was decreased or disappeared after mutation (in KH3111). None DNA relative content other than the growth stages were determinant factors of radioresistance in Deinococcus radiodurans. This results were different from other report (Dickie N et al, 1990). The cellular mechanisms might be the deference's of the bacterium cell morphology between the exponential phase and the stationary phase. Recently, the mutation site of KH3111 which was mutated chemically from wild type KD8301 was identified (Zeji Du, 1998). One base pair changed in the novel gene pprA which was isolated from KD8301 genomic DNA. This point mutation was confirmed to be responsible for the sensitivity of KH3111 to γ-ray and other DNA

  7. Role of lipids in bacterial radioresistance

    International Nuclear Information System (INIS)

    Abushady, M.R.; Fawkia, M.E.; Tawfik, Z.S.

    1992-01-01

    The radioresistance of three bacterial isolates was determined. S. aureus was the most sensitive one (D 1 0 value 0.14 KGy), B. coagulans was moderate resistant (D 1 0 value 3.3 KGy) and the most resistant one was B.megaterium (D 1 0 value 3.7 KGy). Total lipids and lipid patterns of these bacteria were determined and the role of lipids in radioresistance was investigated. Least amount of total lipids was detected in the most sensitive organism (S. aureus). The increase in the bacterial content of total lipids was concomitant with high degrees of radioresistance. The most resistant organism (B. megaterium was characterized by high content of methyl esters of fatty acids, phosphatidylcholine and phosphatidylethanolamine, followed by appreciable amounts in the moderate resistant (B. coagulans) and the least amounts were detected in the most sensitive organism (S.aureus).6 fig., 3 tab

  8. Radioresistance and hypoxic cells

    International Nuclear Information System (INIS)

    Ando, Koichi

    1989-01-01

    Current progress to explore further understanding of tumor hypoxia was reviewed. At subcellular level, hypoxia induces specific proteins, inhibits DNA synthesis as well as initiation of DNA replicon. Radioresistant characteristics of hypoxic cells is questioned in condition where irradiated cells were kept hypoxia during colony formation. Chronically hypoxic cells recovered from the inner layer of V79 multicellular spheroids are more sensitive to radiation than those from the oxic, outer layer. A novel sandwich culture method, which enables to reoxygenate chronic hypoxia, implies that chronically hypoxic cells are less sensitive to radiation after reoxygenation than oxic cells. For in vivo tumor, two types of tumor hypoxia are reported: diffusion-limited, chronic hypoxia and perfusion-limited, acute hypoxia. Evidence supporting the existence of perfusion-limited hypoxia is provided by an elegant method using vital staining and cell sorter. Data of our own laboratory also implies 2 types of tumor hypoxia; fractional hypoxia and incomplete hypoxia. Fractional hypoxia corresponds to a radioresistant tail on a biphasic tumor cell survival curves while tumors with incomplete hypoxia demonstrate only single component with radioresistant characteristics, instead. (author)

  9. Radioresistant canine hematopoietic cells

    International Nuclear Information System (INIS)

    Kawakami, T.G.; Shimizu, J.; Rosenblatt, L.S.; Goldman, M.

    1987-01-01

    Survival of dogs that are continuously exposed to a moderate dose-rate of gamma radiation (10 cGy/day) is dependent on the age of the dog at the time of exposure. Most dogs exposed postpartum to gamma radiation suffered from suppressed hematopoiesis and died of aplasia. On the other hand, none of the in utero-exposed dogs suffered from suppressed hematopoiesis and most became long-term survivors, tolerating 10-fold greater total dose, but dying of myeloproliferative disease (MPD). Using acute gamma irradiation of hematopoietic cells and colony forming unit cell assay (CFU), they observed that a canine hematopoietic cell line established from a myeloid leukemic dog that was a long-term survivor of continuous irradiation was approximately 4-fold more radioresistant than a hematopoietic cell line established from a dog with nonradiation-induced myeloid leukemia or hematopoietic cells from normal canine bone marrow. In utero dogs that are long-term survivors of continuous irradiation have radioresistant hematopoietic cells, and radioresistance that is a constitutive property of the cells

  10. A Rad53 independent function of Rad9 becomes crucial for genome maintenance in the absence of the Recq helicase Sgs1.

    Directory of Open Access Journals (Sweden)

    Ida Nielsen

    Full Text Available The conserved family of RecQ DNA helicases consists of caretaker tumour suppressors, that defend genome integrity by acting on several pathways of DNA repair that maintain genome stability. In budding yeast, Sgs1 is the sole RecQ helicase and it has been implicated in checkpoint responses, replisome stability and dissolution of double Holliday junctions during homologous recombination. In this study we investigate a possible genetic interaction between SGS1 and RAD9 in the cellular response to methyl methane sulphonate (MMS induced damage and compare this with the genetic interaction between SGS1 and RAD24. The Rad9 protein, an adaptor for effector kinase activation, plays well-characterized roles in the DNA damage checkpoint response, whereas Rad24 is characterized as a sensor protein also in the DNA damage checkpoint response. Here we unveil novel insights into the cellular response to MMS-induced damage. Specifically, we show a strong synergistic functionality between SGS1 and RAD9 for recovery from MMS induced damage and for suppression of gross chromosomal rearrangements, which is not the case for SGS1 and RAD24. Intriguingly, it is a Rad53 independent function of Rad9, which becomes crucial for genome maintenance in the absence of Sgs1. Despite this, our dissection of the MMS checkpoint response reveals parallel, but unequal pathways for Rad53 activation and highlights significant differences between MMS- and hydroxyurea (HU-induced checkpoint responses with relation to the requirement of the Sgs1 interacting partner Topoisomerase III (Top3. Thus, whereas earlier studies have documented a Top3-independent role of Sgs1 for an HU-induced checkpoint response, we show here that upon MMS treatment, Sgs1 and Top3 together define a minor but parallel pathway to that of Rad9.

  11. Radioresistance and radiosensitivity in Drosophila melanogaster

    International Nuclear Information System (INIS)

    Reguly, M.L.

    1983-01-01

    Studying the mechanisms controlling radioresistant in Drosophila the sensibility of four strains of Drosophila melanogaster to sex-linked recessive lethal mutations induced by 5kR Cobalt-60 gamma radiation and 0,006 M EMS or 0,25% of caffeine was determined. (M.A.C.) [pt

  12. Radioresistant microorganisms and food irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Ito, H [Japan Atomic Energy Research Inst., Takasaki, Gunma. Takasaki Radiation Chemistry Research Establishment

    1976-01-01

    This paper deals with Micrococcus radiodurans, Arthrobacter radiotolerance, etc., which were isolated and discovered as radioresistant microorganisms. As for the explanation of the mechanism of radioresistance of these microorganisms, the consideration that these organisms have marked repair power of the damaged DNA and have many opportunity to repair the damaged DNA because of their long fission term were cited. The relationship between the radioresistance of microorganisms and food irradiation was also mentioned.

  13. Stress and radioresistance (genetic aspects)

    International Nuclear Information System (INIS)

    Lyubaschevsky, N.M.; Grigorkina, E.B.

    1995-01-01

    Inbred mice and randomly bred stock were exposed to long-term adrenaline and hypothermia stress effects for unification of their functional status, followed by acute total gamma irradiation by equal-effect doses (LD 50/30 ). The significant reduction of lethality distribution in inbred mice after combined stress and radiation effects was observed. The spread of lethality in random bred stock was increased as compared to the control group. The post-irradiation mortality in experimental animals differed only slightly from the values in the control groups. Conclusions are drawn about the principal meaning of genotype in radiosensitivity, about the role of an organism's functional status in determination of death date and about the possible epigenetic structuralisation of linear mice by radioresistance. (Author)

  14. Radioresistance in Central Asian tortoise

    Energy Technology Data Exchange (ETDEWEB)

    Turdyev, A.A.; Bogdanova-Berezovskaya, I.G.; Dvornikova, L.I.

    Season-related studies were conducted on the phenomenal radioresistance of the Central Asian tortoise (Testudo horsfieldii), in order to obtain greater understanding of the factors that determine this physiological uniqueness. Test animals were exposed to gamma radiation from a Co-60 source with dosages ranging from 12.9 to 25.8 Cl/kg in the spring, summer, fall, and winter. Using Pearson's ..gamma..-distribution coefficient calculations of the mean lethal dose for the season yielded 16.33 Cl/kg for winter, 10.94 Cl/kg for spring, 7.1 Cl/kg for summer, and 19.71 Cl/kg for fall. The animals were thus seen to be most susceptible to radiation damage in the spring and summer. Correlation with histological and hematological studies showed that animals irradiated in spring and summer succumbed as a result of damage to the GI and the hematopoietic systems, whereas animals that died as a result of irradiation during the fall and winter season did so because of depletion of hepatic glycogen stores. 5 references, 1 figure.

  15. Survivin as a radioresistance factor in pancreatic cancer

    International Nuclear Information System (INIS)

    Asanuma, Koichi; Moriai, Ryosuke; Yajima, Tomomi; Yagihashi, Atsuhito; Yamada, Mikako; Kobayashi, Daisuke; Watanabe, Naoki

    2000-01-01

    We examined whether survivin acts as a constitutive and inducible radioresistance factor in pancreatic cancer cells. Using a quantitative TaqMan reverse transcription-polymerase chain reaction for survivin mRNA in five pancreatic cancer cell lines, we found an inverse relationship between survivin mRNA expression and radiosensitivity. PANC-1 cells, which had the highest survivin mRNA levels, were most resistant to X-irradiation; MIAPaCa-2 cells, which showed the least survivin mRNA expression, were the most sensitive to X-irradiation. Our results suggested that survivin could act as a constitutive radioresistance factor in pancreatic cancer cells. To determine whether radioresistance is enhanced by induction of survivin expression by irradiation, PANC-1 and MIAPaCa-2 cells were subjected to sublethal doses of X-irradiation followed by a lethal dose. Survivin mRNA expression was increased significantly in both PANC-1 and MIAPaCa-2 cell lines by pretreatment with a sublethal dose of X-irradiation, as was cell survival after exposure to the lethal dose. In this system, enzymatic caspase-3 activity was significantly suppressed in cells with acquired resistance. These results suggest that survivin also acts as an inducible radioresistance factor in pancreatic cancer cells. Survivin, then, appears to enhance radioresistance in pancreatic cancer cells; inhibition of survivin mRNA expression may improve the effectiveness of radiotherapy. (author)

  16. Radiations, human cancerization and radioresistance

    International Nuclear Information System (INIS)

    Vuillaume, M.

    1991-01-01

    Active oxygen species have been implicated in inflammatory diseases, cellular transformation and carcinogenesis. Experiments studying their direct (for instance, by ionizing radiation) or indirect influence (for instance, by the decrease(s) in activity of cellular defence enzymes), in vivo, and/or, in cell cultures (fibroblasts, keratinocytes, hepatocytes,...) have been positive. To the contrary, reactions or products, which decrease level(s) of free radicals/H 2 O 2 (i) directly, (ii) indirectly by an increase of SOD, catalase, and peroxydase activites suppress the above-described phenomena. This is the case for the domain number 2 (that contains copper, MW 53KDa) of the Scorpion's blood pigment (hemocyanin), which possesses SOD-, catalase-, and peroxydase-like properties, resistant to, at least, 4000 Gy, and thus may explain the especially high radioresistance of scorpions. Enzymatic decrease(s) and the domain number 2 of hemocyanin are under current investigation in several laboratories [fr

  17. Establishment of a radioresistant human lung cancer cell subline and its mechanism of radioresistance

    International Nuclear Information System (INIS)

    Zhao Wei; Wang Qiong; Liu Li; Shi Xing; Ding Qian; Wu Gang

    2008-01-01

    Objective: To establish a radioresistant cell subline from a human A549 lung cancer cell line and investigate the mechanism of radioresistance. Methods: Two proposals were applied for the non-small cell lung cancer A549 cells irradiated with X-rays: A group of A549 cell line was irradiated five times, the fractionated dose was 600 cGy, and the other group was exposed 15 times, the fractionated dose was 200 cGy. After the completion of irradiation, two monoclones were obtained from the survival of cells and named the subline A549-S1 and A549-S2. The radiosensitivity and cell cycle distribution of these two clones, together with its parental A549 cells were measured by clone formation assay and flow cytometry. The mRNA and protein levels of Notchl in A549 cell line and the sublines were determined by RT-PCR and Western-blots. Results: Compared with the parental A549 cells, A549-S1 cells showed significant resistance to radiation with D 0 , D q and N values increased, and a broader initial shoulder as well as 1.38-fold increased value of SF 2 . The A549-S1 subline also showed higher percentage of cells in S phase and G 2 /M phase, but lower percentages in G 1 /G 1 phase (P 0 , D q and N values decreased and a curve initial shoulder. The ratio of cells in S and G 0 /G 1 phase ratio was lower than that in parental A549 cells, but that in G 2 /M phase ratio was higher significantly (P<0.05). The expression of Notchl had no marked change compared to A549 cell. Conclusions: The radioresistance of the A549 cell subline is correlated with the irradiation program. The cell subline shows a different cell cycle distribution from their parental line. The cell cycle distribution has a close correlaiton with the expression of Notchl. (authors)

  18. DNA repair mechanism in radioresistant bacteria

    International Nuclear Information System (INIS)

    Kitayama, Shigeru

    1992-01-01

    Many radiation resistant bacteria have been isolated from various sources which are not in high background field. Since Deinococcus radiodurans had been isolated first in 1956, studies on the mechanism for radioresistance were carried out mostly using this bacterium. DNA in this bacterium isn't protected against injury induced by not only ionizing radiation but also ultraviolet light. Therefore, DNA damages induced by various treatments are efficiently and accurately repaired in this cells. Damages in base and/or sugar in DNA are removed by endonucleases which, if not all, are synthesized during postirradiation incubation. Following the endonucleolytic cleavage the strand scissions in DNA are seemed to be rejoined by a process common for the repair of strand scissions induced by such as ionizing radiations. Induce protein(s) is also involved in this rejoining process of strand scissions. DNA repair genes were classified into three phenotypic groups. (1)Genes which are responsible for the endonucleolytic activities. (2) Genes involved in the rejoining of DNA strand scissions. (3) Genes which participate in genetic recombination and repair. Three genes belong to (1) and (2) were cloned onto approximately 1 kbp DNA fragments which base sequences have been determined. (author)

  19. DNA repair mechanism in radioresistant bacteria

    International Nuclear Information System (INIS)

    Kitayama, Shigeru

    1992-01-01

    Many radiation resistant bacteria have been isolated from various sources which are not in high background field. Since Deinococcus radiodurans had been isolated first in 1956, the studies on the mechanism of radioresistance were mostly carried out using this bacterium. DNA in this bacterium isn't protected against injury induced by not only ionizing radiation but also ultraviolet light. Therefore, DNA damages induced by various treatments are efficiently and accurately repaired in this cells. Damages in base and/or sugar in DNA are removed by endonucleases which, if not all, are synthesized during postirradiation incubation. Following the endonucleolytic cleavage the strand scissions in DNA are seemed to be rejoined by a process common for the repair of strand scissions induced by such as ionizing radiations. Induce protein(s) is also involved in this rejoining process of strand scissions. DNA repair genes were classified into three phenotypic groups. (1) Genes which are responsible for the endonucleolytic activities. (2) Genes involved in the rejoining of DNA strand scissions. (3) Genes which participate in genetic recombination and repair. Three genes belong to (1) and (2) were cloned onto approximately 1 kbp DNA fragments which base sequences have been determined. (author)

  20. Thermoresistance in radioresistant strains of 'Drosophila nebulosa'

    International Nuclear Information System (INIS)

    Kratz, F.L.

    1977-01-01

    The detection of thermoresistance in radioresistant strains of 'D. nebulosa' is described, as well as some conclusions on the genetic nature of these differences are presented. The strains used in this experiment were MF 204, from 'Morro de Ferro', in Pocos de Caldas (MG) (one of the biggest radioactive anomalies in the world) whose radioresistance is due to its additive genetic components (Kratz, 1973 and 1975); 85(87) R, an induced radioresistant strain; and MF K a control 'pooled' strain obtained near 'Morro do Ferro'. Survival tests, 72 hours after temperature shocks, performed in the interval of 36 0 C to 39 0 C showed a decreasing gradient of thermoresistance with the following regression coefficients: MF 204 b= - 5,4; 85(87)R b= - 7,2 and MF K b= - 7,9. Bifactorial analysis (strains and sexes) performed at 38 0 C and 39 0 C confirmed differences among strains (P [pt

  1. The problem: Tumor radioresistance in clinical radiotherapy

    International Nuclear Information System (INIS)

    Peters, L.J.; Withers, H.R.; Thames, H.D.; Fletcher, G.H.; M.D. Anderson Hospital and Tumor Inst., Houston, TX)

    1983-01-01

    Tumor radioresistance in clinical radiotherapy implies failure to achieve local-regional disease control with radiation doses producing an acceptable degree of morbidity. Such radioresistance may be due to many different causes (biological and technical) which are reviewed in terms of possible remedial actions. Dose-response relationships for human cancers suggest that, in many sites, tumors are heterogeneous with respect to their cure-limiting characteristics. The case is developed that unless the predominant cure-limiting factor can be predicted, little benefit may be seen in trials of new treatment strategies using heterogeneous tumor populations. The fundamental problem of clinical radioresistance is therefore perceived as the inability to identify predictively its cause in the individual patient

  2. [Unique properties of highly radioresistant bacteria].

    Science.gov (United States)

    Romanovskaia, V A; Rokitko, P V; Malashenko, Iu R

    2000-01-01

    In connection with the Chernobyl Nuclear Power Plant (ChNPP) accident and the negative ecological after-effects for biota in this zone the interest has arisen to radioresistant bacteria, as to the most dynamic model of the given ecosystem, and to mechanisms which provide resistance of bacteria to ionizing radiation. The analysis of published data has shown that the radioresistant bacteria are not interrelated taxonomically and phylogenetically. The extreme radioresistant bacteria are represented by the Deinococcus species, which form a group phylogenetically close to the line Thermus-Meiothermus. Other radioresistant bacteria are the representatives of the genera Rubrobacter, Methylobacterium, Kocuria, Bacillus and some archebacteria. Data on natural habitats, of radioresistant bacteria are not numerous. In a number of cases it is difficult to distinguish their natural habitats, as they were isolated from the samples which were previously exposed to X-ray or gamma-irradiation, or from the ecosystems with the naturally raised radioactivity. To understand the strategy of survival of radioresistant bacteria, we briefly reviewed the mechanism of action of various species of radiation on cells and macromolecules; physiological signs of the cell damage caused by radiation; mechanisms eliminating (repairing) these damages. More details on mechanisms of the DNA repair in D. radiodurans are described. The extreme resistance of D. radiodurans to the DNA damaging factors is defined by 1) repair mechanisms which fundamentally differ from those in other procaryotes; 2) ability to increase the efficiency of a standard set of the DNA repairing proteins. Literary and own data on the effect of radiation on survival of various groups of bacteria in natural ecosystems are summarized. The ecological consequences of the ChNPP accident for soil bacteria in this region were estimated. The reduction of the number of soil bacteria and recession of microbial diversity under the effect of

  3. Isolation of radioresistant microorganisms from a Co/sup 60/ irradiation plant

    International Nuclear Information System (INIS)

    Lezcano, Graciela

    1982-01-01

    The continuos exposition to low doses of gamma irradiation can produce changes in the microflora's radioresistance. In order to obtain information about these possible modifications, the water from the pool used as shielding of the source, as well as the air and the dust in the irradiation chamber of the semi-industrial irradiation plant existing at the Ezeiza Atomic Center were analyzed. The number of microorganisms was determined by filtration techniques and by dilutions. Radioresistance studies of the contaminating microflora were performed. The value of the D/sub 10/ dose was determined in the conditions of highest resistance. A pronounced decrease in the number of microorganisms was observed as a radiation effect in the samples of water and dust, but not in the air samples, this as a consequence of the extractors' action that continually renews the air and the flora in the chamber, thus preventing high-dose exposure. In the air samples no increase of the microorganisms' radioresistance was observed. In the pool water flora, the development of a great radioresistance was observed. A microorganism whose inactivation curve shows a shoulder of 3.2 Mrad was isolated. This high radioresistance could be the result of the continous exposure to low doses during six years. Contrarily, the microorganims of the irradiation chamber's dust did not increase their radioresistance wiht regard to the common contaminants. In the flora of the dust used as a target, two microorganims whose D/sub 10/ were in excess of 400 krad were found; these could be ocassional contaminants. The radioresistant microorganims were isolated and characterized according to Cowan's scheme, the water microorganisms being identified as belonging to the genus Corynebacterium and the earth ones to the genera Micrococcus and Corynebacterium. (author) [es

  4. Radioresistance of immunized animals in internal irradiation

    International Nuclear Information System (INIS)

    Kal'nitskij, S.A.; Ponomareva, T.V.; Shubik, V.M.

    1981-01-01

    The influence of an immunization with bacterial vaccines and antimeasles-gamma-globulin on the radioresistance of raceless white mice was studied. In the vaccinated animals a higher survival rate and duration of life, a better general condition and a better curve of weight and stronger physical stamina were stated compared to the merely irradiated mice. The higher radioresistance is ascribed to the stimulation of cellular and humoral factors of the unspecific protection against infection, to the repair of the lymphoid tissue of the immunized animals and to the decrease in autosensibilization. (author)

  5. Radioresistance and radiosensitivity in Drosophila melanogaster

    International Nuclear Information System (INIS)

    Reguly, M.L.; Marques, E.K.

    1987-01-01

    The mechanisms of radioresistance in Drosophila are studied. The mutagenic effects of 5KR of 60 Cobalt gamma radiation and of 0,006M dose of ethyl methanesulfonate (EMS) on four D. Melanogaster strains (RC 1 , CO 3 , BUE and LEN) are investigated. (M.A.C.) [pt

  6. Fractionated irradiation-induced EMT-like phenotype conferred radioresistance in esophageal squamous cell carcinoma

    Science.gov (United States)

    Zhang, Hongfang; Luo, Honglei; Jiang, Zhenzhen; Yue, Jing; Hou, Qiang; Xie, Ruifei; Wu, Shixiu

    2016-01-01

    The efficacy of radiotherapy, one major treatment modality for esophageal squamous cell carcinoma (ESCC) is severely attenuated by radioresistance. Epithelial-to-mesenchymal transition (EMT) is a cellular process that determines therapy response and tumor progression. However, whether EMT is induced by ionizing radiation and involved in tumor radioresistance has been less studied in ESCC. Using multiple fractionated irradiation, the radioresistant esophageal squamous cancer cell line KYSE-150R had been established from its parental cell line KYSE-150. We found KYSE-150R displayed a significant EMT phenotype with an elongated spindle shape and down-regulated epithelial marker E-cadherin and up-regulated mesenchymal marker N-cadherin in comparison with KYSE-150. Furthermore, KYSE-150R also possessed some stemness-like properties characterized by density-dependent growth promotion and strong capability for sphere formation and tumorigenesis in NOD-SCID mice. Mechanical studies have revealed that WISP1, a secreted matricellular protein, is highly expressed in KYSE-150R and mediates EMT-associated radioresistance both in ESCC cells and in xenograft tumor models. Moreover, WISP1 has been demonstrated to be closely associated with the EMT phenotype observed in ESCC patients and to be an independent prognosis factor of ESCC patients treated with radiotherapy. Our study highlighted WISP1 as an attractive target to reverse EMT-associated radioresistance in ESCC and can be used as an independent prognostic factor of patients treated with radiotherapy. PMID:27125498

  7. Fractionated irradiation-induced EMT-like phenotype conferred radioresistance in esophageal squamous cell carcinoma

    International Nuclear Information System (INIS)

    Zhang, Hongfang; Luo, Honglei; Jiang, Zhenzhen; Yue, Jing; Hou, Qiang; Xie, Ruifei; Wu, Shixiu

    2016-01-01

    The efficacy of radiotherapy, one major treatment modality for esophageal squamous cell carcinoma (ESCC) is severely attenuated by radioresistance. Epithelial-to-mesenchymal transition (EMT) is a cellular process that determines therapy response and tumor progression. However, whether EMT is induced by ionizing radiation and involved in tumor radioresistance has been less studied in ESCC. Using multiple fractionated irradiation, the radioresistant esophageal squamous cancer cell line KYSE-150R had been established from its parental cell line KYSE-150. We found KYSE-150R displayed a significant EMT phenotype with an elongated spindle shape and down-regulated epithelial marker E-cadherin and up-regulated mesenchymal marker N-cadherin in comparison with KYSE-150. Furthermore, KYSE-150R also possessed some stemness-like properties characterized by density-dependent growth promotion and strong capability for sphere formation and tumorigenesis in NOD-SCID mice. Mechanical studies have revealed that WISP1, a secreted matricellular protein, is highly expressed in KYSE-150R and mediates EMT-associated radioresistance both in ESCC cells and in xenograft tumor models. Moreover, WISP1 has been demonstrated to be closely associated with the EMT phenotype observed in ESCC patients and to be an independent prognosis factor of ESCC patients treated with radiotherapy. Our study highlighted WISP1 as an attractive target to reverse EMT-associated radioresistance in ESCC and can be used as an independent prognostic factor of patients treated with radiotherapy

  8. Development of radiation countermeasure using novel radioresistant bacteria

    International Nuclear Information System (INIS)

    Kumar, Raj; Singh, Shravan K.; Malhotra, Poonam; Gupta, Ashutosh K.; Singh, Praveen K.; Chhachhia, Neha

    2014-01-01

    Radioresistant bacteria sustain their lives in extreme radiation environment and have capabilities to combat radiation induced oxidative stress. Therefore, factors associated with radioresistancy in bacteria may also provide trans-species radioprotection. To test this hypothesis, present work was initiated at INMAS long back. With this background a novel radioresistant bacterium Bacillus sp. INM-1 isolated and its novel secondary metabolite i.e. Semiquinone Glucoside Derivative (SQGD) carrying radioprotective capabilities was purified. SQGD was evaluated for its free radical scavenging, protein, enzymes, plasmid and biological membranes radioprotection capabilities in vitro. SQGD was also tested for its whole body radioprotective efficacy using oral route of administration. Systemic radioprotection offered by SQGD to gastrointestinal, haematopoietic and male reproductive system was studied. Modulation in endogenous antioxidant enzymes and cytoprotective cytokines expression upon irradiation and SQGD pretreatment was determined. A laboratory process for chemical synthesis of bacterial radioprotective molecule has also been developed (Patent filed No. 2075/DEL/2014). Results of the study demonstrated that SQGD efficiently scavenge free radicals in vitro. SQGD provides excellent protection to structural and functional proteins, plasmid DNA and biomembranes against radiation induced oxidative damage. SQGD was observed to offer ∼ 83% whole body survival to lethally irradiated mice when administered 2h before irradiation by oral route. SQGD was found to ensure significant radioprotection to gastro-intestinal, hematopoietic and male reproductive system of irradiated mice. Protein expression studies revealed that SQGD pretreatment to the irradiated mice significantly increased expression of G-CSF, GM-CSF, MCSF; NFkB, IL-2, IL-12, IL-23, IL-6, PCNA and PARP. In conclusion, present study decisively justified the radioprotective potential of bacterial metabolite SQGD

  9. Radioresistance increase in polymers at high pressures

    International Nuclear Information System (INIS)

    Milinchuk, V.; Kirjukhin, V.; Klinshpont, E.

    1977-01-01

    The effect was studied of very high pressures ranging within 100 and 2,700 MPa on the radioresistance of polytetrafluoroethylene, polypropylene and polyethylene in gamma irradiation. For experiments industrial polymers in the shape of blocks, films and fibres were used. It is shown that in easily breakable polymers, such as polytetrafluoroethylene and polypropylene 1.3 to 2 times less free radicals are formed as a result of gamma irradiation and a pressure of 150 MPa than at normal pressure. The considerably reduced radiation-chemical formation of radicals and the destruction suppression by cross-linking in polymers is the evidence of the polymer radioresistance in irradiation at high pressures. (J.B.)

  10. Radioresistance and immunization effectiveness under internal irradiation

    International Nuclear Information System (INIS)

    Kal'nitskij, S.A.

    1978-01-01

    The effect of preliminary immunization on the radioresistance of mice to internal irradiation from incorporated 137 Cs or 90 Sr was studied, and it was found that a preliminary single immunization with bacterial vaccines had a favorable effect on the outcome of radiation injury. The present results suggested that vaccination had a very pronounced radioprotective effect and so may be used as a means of biologic protection from internal irradiation

  11. Ivastimul used to increase radioresistance of mice

    International Nuclear Information System (INIS)

    Rotkovska, D.; Vacek, A.; Bartonickova, A.

    1989-01-01

    A study was made of the effect of ivastimul (IS), an aqueous extract from unicellular Chlorella algae, on the radioresistance and some haemopoiesis parameters of mice exposed to 60 Co-γ-radiation. With median and absolutely lethal radiation doses, IS was shown to produce a pronounced protective effect displayed by the increased survival rate. With sublethal doses, IS elevated the postirradiation formation of endogenous colonies and restoration of bone marrow and spleen cellularity and spleen mass

  12. Radioresistance of human glioma spheroids and expression of HSP70, p53 and EGFr

    International Nuclear Information System (INIS)

    Fedrigo, Carlos A; Rocha, Adriana B da; Grivicich, Ivana; Schunemann, Daniel P; Chemale, Ivan M; Santos, Daiane dos; Jacovas, Thais; Boschetti, Patryck S; Jotz, Geraldo P; Filho, Aroldo Braga

    2011-01-01

    Radiation therapy is routinely prescribed for high-grade malignant gliomas. However, the efficacy of this therapeutic modality is often limited by the occurrence of radioresistance, reflected as a diminished susceptibility of the irradiated cells to undergo cell death. Thus, cells have evolved an elegant system in response to ionizing radiation induced DNA damage, where p53, Hsp70 and/or EGFr may play an important role in the process. In the present study, we investigated whether the content of p53, Hsp70 and EGFr are associated to glioblastoma (GBM) cell radioresistance. Spheroids from U-87MG and MO59J cell lines as well as spheroids derived from primary culture of tumor tissue of one GBM patient (UGBM1) were irradiated (5, 10 and 20 Gy), their relative radioresistance were established and the p53, Hsp70 and EGFr contents were immunohistochemically determined. Moreover, we investigated whether EGFr-phospho-Akt and EGFr-MEK-ERK pathways can induce GBM radioresistance using inhibitors of activation of ERK (PD098059) and Akt (wortmannin). At 5 Gy irradiation UGBM1 and U-87MG spheroids showed growth inhibition whereas the MO59J spheroid was relatively radioresistant. Overall, no significant changes in p53 and Hsp70 expression were found following 5 Gy irradiation treatment in all spheroids studied. The only difference observed in Hsp70 content was the periphery distribution in MO59J spheroids. However, 5 Gy treatment induced a significant increase on the EGFr levels in MO59J spheroids. Furthermore, treatment with inhibitors of activation of ERK (PD098059) and Akt (wortmannin) leads to radiosensitization of MO59J spheroids. These results indicate that the PI3K-Akt and MEK-ERK pathways triggered by EGFr confer GBM radioresistance

  13. Study of radioresistance of microorganisms

    International Nuclear Information System (INIS)

    Olbrichova, D.

    1983-01-01

    Strain radiosensitivity was evaluated on the basis of the determination of inactivation curve parameters and the determination of the D 10 value. The course of curves was investigated for two 60 Co sources, RCHM-gamma-20 (USSR) with an activity of 2.54x10 14 Bq and AECL (type J-6000, Canada) with an activity of 4.92x10 16 Bq. The curve parameters were determined for microorganisms in buffer medium and for cultures in dehydrated condition. Coccus germs were irradiated with doses of 1, 2, 3, 4, 5 and 6 kGy and aerobic sporulates with doses of 3, 6, 9, 12 and 15 kGy. For comparing the resistance of isolated strains the t-test was used. The most resistant of the isolated strains were Bacillus cereus, Bacillus subtilis, Bacillus pumilus and Bacillus megatherium. (E.S.)

  14. The mechanisms of Micrococcus radiodurans radioresistance

    International Nuclear Information System (INIS)

    Samojlenko, I.I.

    1983-01-01

    Modern representations on molecular mechanisms of Micrococcus radiodurans viability under the effect of ionizing radiation have been considered. Factors conditioning a high level of micrococcus cell radiostability have been analyzed: peculiarities of structure of a cell wall, DNA, membranes; excess of genetic information; multiplicity of DNA implantation points to a membrane; high level of antioxidation and antiradical systems. It has been shown that on efficiency of accurate, properly balanced system of DNA repair combined with above Micrococcus radiodurant properties provide a high microorganism radioresistance

  15. Postradiation recovery and radioresistance of seeds

    International Nuclear Information System (INIS)

    Atayan, R.R.; Semerdzhyan, S.P.

    1990-01-01

    Problems on radiobiology of seeds were studied. Irradiation was shown to induce primary injuries in chromosomes sensitive to various modifying factors. Primary injuries can eliminate and form stable physico-chemical injuries as a result of physico-chemical reactions and under concomitant factors. These injuries can be reversible and nonreversible character. Reversible injuries turned out to be potential for they can be repaired at biochemical level. The cells of strong ability to repair postirradiation injuries under various equal conditions reveal a relatively high level of radioresistance. The mechanisms were shown to be basical in the observed differences of radiosensitivity of large and small seeds. 7 refs.; 3 figs

  16. Criteria for estimation of radioresistance of testudo horsfieldi

    Energy Technology Data Exchange (ETDEWEB)

    Turdyev, A.A.; Bogdanova-Berezovskaya, I.G.; Dvornikova, L.I. (AN Uzbekskoj SSR, Tashkent. Inst. Zoologii i Parazitologii)

    A study was made of a phenomenal radioresistance of Testudo horsfieldi. The authors described the features of the postirradiation death at different seasons. A threshold number of the affected systems in the turtles was one order lower than that of mammals. A positive correlaton was found between specific affection of the systems and the degree of their radioresistance.

  17. Nuclear medicine markers of tumor oxygenation and radioresistance

    International Nuclear Information System (INIS)

    Chapman, J. Donald; Schneider, R.H.; Stobbe, C.C.; Kim, E.; Engelhardt, E.L.; Coia, L.

    1996-01-01

    Purpose/Objective: The objective of this research project was to synthesize, purify, radiolabel and characterize second-generation nuclear medicine markers of tissue oxygenation with properties superior to iodoazomycin arabinoside (IAZA) and to validate the hypoxia-marking activity of optimal compounds by independent measurements of tumor oxygenation and tumor radioresistance. Materials and Methods: Six hypoxic markers of the iodoazomycin nucleoside class with water solubilities greater than IAZA were synthesized by published procedures. The markers were purified, chemically characterized and labeled with Iodine-125 or Iodine-131. Absolute rates of marker ligation to the macromolecules of hypoxic EMT-6 tumor cells in vitro were determined as a function of marker concentration and used to establish relative marker effectiveness. Hypoxic marking activity in tumors was determined from tumor/blood (T/B) and tumor/muscle (T/M) ratios of radiolabelled marker in EMT-6 tumor-bearing C.B17/Icr scid mice. The optimal marker was administered to R3327-H and R3327-AT tumor-bearing Fischer X Copenhagen rats for estimates of tumor oxygenation by T/B and T/M ratios. Oxygen distributions in the same tumors were obtained with the Eppendorf pO 2 Histograph. The radioresistance of individual tumors was determined from in vitro plating efficiencies of cells released from tumors which had been irradiated in vivo with 20 Gy Cs-137 γ-rays. Results: Of the six iodinated azomycin nucleosides investigated, five were novel markers and all had water solubilities higher than IAZA. Iodinated azomycin xylopyranoside (β-D-IAZXP) was selected as the optimal marker of this class since it 1) exhibited the highest absolute rate of ligation to hypoxic tumor cells in vitro, 2) had the fastest plasma clearance rate in tumor-bearing mice and 3) yielded high T/B ratios in both the mouse and rat tumor models employed in this study. Planar nuclear medicine images of (I-131) β-D-IAZXP in tumor-bearing rats

  18. Gene expression profile associated with radioresistance and malignancy in melanoma

    International Nuclear Information System (INIS)

    Ibañez, I.L.; Molinari, B.; Notcovich, C.; García, F.M.; Bracalente, C.; Zuccato, C.F.; Durán, H.

    2015-01-01

    The incidence of melanoma has substantially increased over the last decades. Melanomas respond poorly to treatments and no effective therapy exists to inhibit its metastatic spread. The aim of this study was to evaluate the association between radioresistance of melanoma cells and malignancy. A melanoma model developed in our laboratory from A375 human amelanotic melanoma cells was used. It consists in two catalase-overexpressing cell lines with the same genetic background, but with different phenotypes: A375-A7, melanotic and non-invasive and A375-G10, amelanotic and metastatic; and A375-PCDNA3 (transfected with empty plasmid) as control. Radiosensitivity was determined by clonogenic assay after irradiating these cells with a “1”3”7 Cs gamma source. Survival curves were fitted to the linear-quadratic model and surviving fraction at 2 Gy (SF2) was calculated. Results showed that A375-G10 cells were significantly more radioresistant than both A375-A7 and control cells, demonstrated by SF2 and α parameter of survival curves: SF2=0.32±0.03, 0.43±0.16 and 0.89±0.05 and α=0.45±0.05, 0.20±0.05 and 0 for A375-PCDNA3, A375-A7 and A375-G10 respectively. Bioinformatic analysis of whole genome expression microarrays data (Affymetrix) from these cells was performed. A priori defined gene sets associated with cell cycle, apoptosis and MAPK signaling pathway were collected from KEGG (Kyoto Encyclopedia of Genes and Genomes) to evaluate significant differences in gene set expression between cells by GSEA (Gene Set Enrichment Analysis). A375-G10 showed significant decrease in the expression of genes related to DNA damage response (ATM, TP53BP1 and MRE11A) compared to A375-A7 and controls. Moreover, A375-G10 exhibited down-regulated gene sets that are involved in DNA repair, checkpoint and negative regulation of cell cycle and apoptosis. In conclusion, A375-G10 gene expression profile could be involved in radioresistance mechanisms of these cells. Thus, this expression

  19. Studies on radioresistance with HeLa cells

    International Nuclear Information System (INIS)

    Koiwai, Soichiro; Muta, Nobuyoshi

    1980-01-01

    In our previous experiments (15, 16), HeLa cells were successively irradiated with 1 kR of X-rays. After receiving 3, 5, 8, 11, 14, and 17 kR the iradiated HeLa cells showed progressively increasing radioresistance. In the present paper, the results of studies on the variation of the extrapolation number (n), mean lethal dose (D sub(o)), and quasi-threshold dose (D sub(q)) of survival curves for these radioresistant HeLa strains were reported. The values of n of the original and radioresistant strains were all found between 2 and 3, and a change of the n values with an increase in the total dose received by the cell strains was not noticed. On the other hand, the values of D sub(o) of the radioresistant strains progressively increased from 105 R in the original line to 148 R in the 17 kR strain with increasing doses of pre-irradiation. Similarly, the values of D sub(q) had a tendency to increase in the radioresistant strains. Repair of sublethal damage with the original and radioresistant strains was studied and the properties of the radioresistant strains were discussed. (author)

  20. Establishment of clinically relevant radioresistant cell lines and their characteristics

    International Nuclear Information System (INIS)

    Fukumoto, Manabu; Kuwahara, Yoshikazu; Suzuki, Masatoshi

    2014-01-01

    Although radiotherapy is one of the major therapeutic modalities for eradicating malignant tumors, the existence of radioresistant cells remains one of the most critical obstacles. Standard radiotherapy consists of fractionated radiation (FR) of 2-Gy X-rays once a day, 5 days a week, over 60 Gy in total. To understand the characteristics of radioresistant cells and to develop more effective radiotherapy, we have established novel radioresistant cell lines by long-term (> 5 years) exposure to moderate doses of fractionated X-rays. While all the parental human cancer cells ceased, their radioresistant derivatives continue to proliferate with daily exposure to 2-Gy FR for more than 30 days. We have coined those cells as 'clinically relevant radioresistant' (CRR) cells. Transplanted tumors into nude mice were also CRR, indicating that CRR cell lines are powerful tools to improve cancer radiotherapy. We have shown that the suppression of autophagic cell death but not apoptosis was mainly involved in cellular radioresistance. An inhibitor of the mTOR pathway which enhances autophagy was effective to overcome CRR tumors induced in nude mice. But the underlined mechanism was not through the inhibition of autophagy. Guanine nucleotide-binding protein 1 (GBP1) over expression was necessary for maintaining the CRR phenotype, but radioresistant cells were not necessarily cancer stem cells (CSCs). Targeting GBP1 positive cancer cells may be a more efficient method in conquering cancer than targeting CSCs. Slight but significant radioresistance was acquired by 0.5 Gy/12 hrs of long-term FR exposures to parental cells for more than 31 days in accordance with cyclinD1 over expression. This acquired radioresistance (ARR) was stably maintained in the tumor cells even on 31 days after the cessation of 0.5-Gy FR. Present observations give a mechanistic insight for ARR of tumor cells through long-term FR exposure, and provide novel therapeutic targets for radiosensitization

  1. Role of endogenous substances in enhancing radioresistance background

    International Nuclear Information System (INIS)

    Goncharenko, E.N.; Gorskaya, T.G.; Gudz', T.I.; Zolotareva, L.T.; Kovaleva, Z.I.; Peshkova, E.N.

    1978-01-01

    It is shown that in Saccharomyces cerevisiae of ''wild type'' diploid cells (more radioresistant than haploid ones) are characterized by a higher content of endogenous biologically active substances, which possess a radioprotective ability (biogenous amines and SOD), and a lower level of radiosensitizing substances (hydroperoxides of higher unsaturated fatty acids). With Saccharomyces cerevisiae, bearing mutation rad 51, not all the components of the radioresistance background shoW this dependence, which is indicative of the presence of additional factors affecting radioresistance of these cells

  2. The nature of variations in the radioresistance of sea urchin eggs in the early embryogenesis

    International Nuclear Information System (INIS)

    Konstantinova, M.M.; Tarasenko, A.G.; Nekrasova, I.V.; Dontsova, G.V.

    1975-01-01

    The synchronously developing sea urchin eggs (Strongylocentrotus nudus) have been used for the experiment. Radioprotective efficiency of cysteamine (applied in the concentrations ranging from 1.10 -5 to 5.10 -3 M) has been studied at two stages of mitosis: metaphase and telophase. Cysteamine (5.10 -3 M) has been found to level the variations in radiosensitivity of these phases producing the strongest effect in the radiosensitive phase (telophase) and the slightest effect in the radioresistant phase (metaphase). Determination of the relative protective effectiveness of cysteamine in relation to the original radiosensitivity of a cell, and, hence, to its thiol content, has demonstrated that the higher the radiosensitivity of a cell at the time of the exposure the higher the relative protective efficiency of cysteamine. The data obtained evidence of the idea that thiols play an essential role in the determination of radioresistance of different stages of mitosis of the developing sea urchin eggs

  3. A change in radioresistance of barley under chronic irradiation

    International Nuclear Information System (INIS)

    Kal'chenko, V.A.; Shevchenko, V.A.; Fedotov, I.S.

    1981-01-01

    Mutation process and radioresistance of barley growing in an area with increased radiation background (beta radiation doss -0.6 R/day) have been analyzed. Experimental material is given with 250 kindred families where aberration level of chromosomes was analyzed in mitosis and meiosis during 4 years. It is shown that the first generations (M 1 -M 2 ) in experimental material demonstrate an increased level of structural mutations of chromosomes, while the subsequent generations (M 3 -M 4 ) demonstrate the level reduced to control. A higher radioresistance is observed in M 5 plants of chronically irradiated version as compared to nonirradiated version. It is suggested that increase in radioresistance results from the stimulation of repair systems with low doses of chronic irradiation as well as from the selection of a more radioresistant forms out of the population [ru

  4. γ-irradiation induces radioresistant DNA synthesis in HeLa cells

    International Nuclear Information System (INIS)

    Synzynys, B.I.; Aminev, A.G.; Konstantinova, S.A.; Saenko, A.S.

    1987-01-01

    Cells of suspension HeLa culture at the logarithmic phase of growth were exposed to 60 Co-γ-rays (5 Gy), incubated in the nutritious medium, and in 4 h subjected to repeated irradiation: the dose-response function and the dynamics of DNA synthesis inhibition were determined. It was shown that DNA synthesis was inhibited to a lesser extent after preirradiation, in other words, DNA synthesis was radioresistant. A correlation between this synthesis and reproductive cell death is discussed

  5. Radioresistance-related signaling pathways in nasopharyngeal carcinoma cells

    International Nuclear Information System (INIS)

    Guo Ya; Zhu Xiaodong; Qu Song; Su Fang; Wang Qi; Zhang Wei

    2011-01-01

    Objective: To study the difference of gene expression profile between the radioresistant human nasopharyngeal carcinoma cell line CNE-2R and CNE-2, and to screen the signaling pathway associated with radioresistance of nasopharyngeal carcinoma. Methods: The radioresistant nasopharyngeal carcinoma cell line CNE-2R was constructed from the original cell line CNE-2. CNE-2R and CNE-2 cells were cultured and administered with 60 Co γ-ray irradiation at the dose of 400 cGy for 15 times. Human-6v 3.0 whole genome expression profile was used to screen the differentially expressed genes. Bioinformatic analysis was used to identify the pathways related to radioresistance. Results: The number of the differentially expressed genes that were found in these 2 experiments was 374. The Kegg pathway and Biocarta pathway analysis of the differentially expressed genes showed the biological importance of Toll-like receptor signaling pathway and IL-1 R-mediated signal transduction pathway to the radioresistance of the CNE-2R cells and the significant differences of 13 genes in these 2 pathways,including JUN, MYD88, CCL5, CXCL10, STAT1, LY96, FOS, CCL3, IL-6, IL-8, IL-1α, IL-1β, and IRAK2 (t=13.47-66.57, P<0.05). Conclusions: Toll-like receptor signaling pathway and IL-1R-mediated signal transduction pathway might be related to the occurrence of radioresistance. (authors)

  6. Characterization of radioresistant variant from U251 human glioblastoma cell line and the role of antioxdant enzymes in its radioresistancy

    International Nuclear Information System (INIS)

    Lee, Hyung Chahn; Park, In Chul; Park, Myung Jin; Woo, Sang Hyeok; Rhee, Chang Hum; Hong, Seok-II

    2004-01-01

    To investigate the radioresistant mechanism in glioblastoma multiforme(GBM), we isolated the radioresistant clone (RRC) from U251 human glioblastoma cell line by exposing to repeated fractions of 3 Gy γ-radiation for six months. RRC had higher radioresistance than the parent cell line as measured by clonogenic survival assay. FACS analysis showed that RRC had a delayed G2 arrest after radiation. Antioxidant enzymes, such as SOD, catalase, glutathione peroxidase (GPX), glutathione reductase (GR), were activated up to 5 folds in RRC after radiation. Erk 1/2 activation was higher in RRC than in the parent cell. Therefore, radioresistancy in RRC might be due to the delayed cell cycle, the coordinated high activation of antioxidant enzyme rather than a single enzyme alone,and higher activation of Erk 1/2

  7. Cytotoxicity and radiosensitization effect of TRA-8 on radioresistant human larynx squamous carcinoma cells.

    Science.gov (United States)

    Wu, F; Hu, Y; Long, J; Zhou, Y J; Zhong, Y H; Liao, Z K; Liu, S Q; Zhou, F X; Zhou, Y F; Xie, C H

    2009-02-01

    TRAIL induces apoptosis in a variety of tumorigenic and transformed cell lines, but not in many normal cells. Recent studies have demonstrated that death receptor 5 (DR5), one of the two death receptors bound by TRAIL, showed expression in most malignantly transformed cells. This study evaluated effects of a monoclonal antibody (TRA-8) to human death receptor 5, combined with ionizing radiation, on radioresistant human larynx squamous carcinoma cell line (Hep-2R). Cells were treated with TRA-8 alone or in combination with radiation, cell viability inhibition was measured by MTT assay, and the induction of apoptosis was determined by Annexin V staining. Radionsensitivity of Hep-2R cells treated with TRA-8 were investigated with long-term clonogenic assays. Regulation of DR5 expression in cells after radiation was analyzed by indirect immunofluorescence using murine TRA-8 in combination with flow cytometry. The results suggested that TRA-8 enhanced radionsensitivity of Hep-2R cells, and that TRA-8 regulated Hep-2R cell cycle arrest at G2/M phase. Irradiation up-regulated the expression of DR5, and when combined with TRA-8 yielded optimal survival benefit. Therefore, TRA-8 can be used in combination with irradiation in radioresistant human larynx squamous carcinoma cells. Monoclonal antibodies such as TRA-8 may play an important role in the development of an effective treatment strategy for patients with radioresistant cancers.

  8. Putative radioresistant bacterial isolate from sewage water

    International Nuclear Information System (INIS)

    Ang, April; Chua, Patricia; Perez, Kristine; Rey, April; Rivor Kristel; San Pablo, Czarina; Santos, Ernestine

    2001-01-01

    Sewage water was collected from a stagnant body of water in Balara, Quezon City. approximately 150 ml was aseptically transferred into eight Erlenmeyer flasks. Seven flasks were then subjected to different doses of radiation at the 60 Co irradiation facility, PNRI (Philippine Nuclear Research Institute) which are as follows: 0.01 kGy, 0.1 kGy, 0.5 kGy, 1 kGy, 5 kGy, 10 kGy, and 15 kGy. The remaining flask was used as the control. After irradiation, all the different treatments were subjected to colony count at the culture collection laboratory, NSRI. Results showed that the colonies from sewage water treatments irradiated at 0.01 kGy (treatment A), 0.10 kGy (treatment B), and 0.50 kGy (treatment C) exhibited a decreasing trend with colony counts 4.60 x 10 3 CFU/ml, and 1.30 x 10 3 CFU/ml, and 26 CFU/ml, respectively. Contrastingly, at 1 kGy (treatment D), high colony count of 2.95 x 10 3 CFU/ml was observed which is even higher compared to the control (1.02 x 10 3 CFU/ml). Treatment E that was irradiated at 5 kGy manifested low survival rate (25 CFU/ml) indicating the presence of few putative intermediate radioresistant bacteria. Radiation dose treatments higher than 5 kGy (i.e., 10 kGy and 15 kGy) exhibited no bacterial survival. (Author)

  9. Putative radioresistant bacterial isolate from sewage water

    Energy Technology Data Exchange (ETDEWEB)

    Ang, April; Chua, Patricia; Perez, Kristine; Rey, April; Kristel, Rivor; San Pablo, Czarina; Santos, Ernestine

    2001-01-29

    Sewage water was collected from a stagnant body of water in Balara, Quezon City. approximately 150 ml was aseptically transferred into eight Erlenmeyer flasks. Seven flasks were then subjected to different doses of radiation at the {sup 60}Co irradiation facility, PNRI (Philippine Nuclear Research Institute) which are as follows: 0.01 kGy, 0.1 kGy, 0.5 kGy, 1 kGy, 5 kGy, 10 kGy, and 15 kGy. The remaining flask was used as the control. After irradiation, all the different treatments were subjected to colony count at the culture collection laboratory, NSRI. Results showed that the colonies from sewage water treatments irradiated at 0.01 kGy (treatment A), 0.10 kGy (treatment B), and 0.50 kGy (treatment C) exhibited a decreasing trend with colony counts 4.60 x 10{sup 3} CFU/ml, and 1.30 x 10{sup 3} CFU/ml, and 26 CFU/ml, respectively. Contrastingly, at 1 kGy (treatment D), high colony count of 2.95 x 10{sup 3} CFU/ml was observed which is even higher compared to the control (1.02 x 10{sup 3} CFU/ml). Treatment E that was irradiated at 5 kGy manifested low survival rate (25 CFU/ml) indicating the presence of few putative intermediate radioresistant bacteria. Radiation dose treatments higher than 5 kGy (i.e., 10 kGy and 15 kGy) exhibited no bacterial survival. (Author)

  10. Properties of bacterial radioresistance observed in sewage sludge

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, H; Ito, H; Takehisa, M [Japan Atomic Energy Research Inst., Takasaki, Gunma. Takasaki Radiation Chemistry Research Establishment; Iizuka, H

    1981-09-01

    The changes in radiosensitivities of bacteria in sludge were investigated. The coliforms are more radioresistant in raw sludge than in cake (dewatered sludge). This radioresistance of coliforms was observed not only in raw sludge but also in the cake diluted with water. The radioresistance was independent of the difference of treatment plant, kind of sludge, and season. The oxygen effect on the radioresistance was not observed, but the resistance was changed during storage of sludge. Escherichia coli isolated from sludge was radiosensitive in buffer, but its radiosensitivity was protected by the water-extracts of sludge. On the other hand, radioresistant bacteria were present in total bacteria of sludge irradiated at 2 Mrad. However, the dominant flora in the irradiated sludge consisted of radiosensitive bacteria (mainly Pseudomonas). When a strain of radiosensitive Pseudomonas was irradiated in raw sludge and diluted cake, the radiosensitivity was remarkably protected. From these results, it is suggested that a factor affecting the radiosensitivity of bacteria is present in sludge.

  11. Properties of bacterial radioresistance observed in sewage sludge

    International Nuclear Information System (INIS)

    Watanabe, Hiroshi; Ito, Hitoshi; Takehisa, Masaaki; Iizuka, Hiroshi.

    1981-01-01

    The changes in radiosensitivities of bacteria in sludge were investigated. The coliforms are more radioresistant in raw sludge than in cake (dewatered sludge). This radioresistance of coliforms was observed not only in raw sludge but also in the cake diluted with water. The radioresistance was independent of the difference of treatment plant, kind of sludge, and season. The oxygen effect on the radioresistance was not observed, but the resistance was changed during storage of sludge. Escherichia coli isolated from sludge was radiosensitive in buffer, but its radiosensitivity was protected by the water-extracts of sludge. On the other hand, radioresistant bacteria were present in total bacteria of sludge irradiated at 2 Mrad. However, the dominant flora in the irradiated sludge consisted of radiosensitive bacteria (mainly Pseudomonas). When a strain of radiosensitive Pseudomonas was irradiated in raw sludge and diluted cake, the radiosensitivity was remarkably protected. From these results, it is suggested that a factor affecting the radiosensitivity of bacteria is present in sludge. (author)

  12. Cancer-associated adipocytes promotes breast tumor radioresistance

    Energy Technology Data Exchange (ETDEWEB)

    Bochet, Ludivine; Meulle, Aline [Universite de Toulouse, UPS, F-31077 Toulouse Cedex (France); CNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale), 205 route de Narbonne, BP 64182, F-31077 Toulouse Cedex (France); Institut National de la Sante et de la Recherche Medicale, INSERM U1048, 1 Avenue du Pr Jean Poulhes, BP 84225, F-31432 Toulouse Cedex (France); Imbert, Sandrine [CNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale), 205 route de Narbonne, BP 64182, F-31077 Toulouse Cedex (France); Salles, Bernard [Universite de Toulouse, UPS, F-31077 Toulouse Cedex (France); CNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale), 205 route de Narbonne, BP 64182, F-31077 Toulouse Cedex (France); Valet, Philippe [Universite de Toulouse, UPS, F-31077 Toulouse Cedex (France); Institut National de la Sante et de la Recherche Medicale, INSERM U1048, 1 Avenue du Pr Jean Poulhes, BP 84225, F-31432 Toulouse Cedex (France); Muller, Catherine, E-mail: muller@ipbs.fr [Universite de Toulouse, UPS, F-31077 Toulouse Cedex (France); CNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale), 205 route de Narbonne, BP 64182, F-31077 Toulouse Cedex (France)

    2011-07-22

    Highlights: {yields} Tumor-surrounding adipocytes contribute to breast cancer progression. {yields} Breast tumor cells previously co-cultivated with mature adipocytes exhibit radioresistance. {yields} Increased in Chk1 phosphorylation is observed in irradiated co-cultivated tumor cells. {yields} IL-6 is over-expressed in tumor cells co-cultivated with adipocytes. {yields} IL-6 exposure confers increased Chk1 phosphorylation and radioresistance in tumor cells. -- Abstract: Mature adipocytes are excellent candidates to influence tumor behavior through heterotypic signaling processes since these cells produce hormones, growth factors, cytokines and other molecules, a heterogeneous group of molecules named adipokines. Using a 2D coculture system, we demonstrate that breast tumor cells previously co-cultivated with mature adipocytes exhibit radioresistance and an earlier and higher increase in the effector kinase Chk1, a phenotype that was associated with decreased cell death as compared to tumor cells grown alone. Interestingly, the adipocytes-induced tumor changes taking place during the coculture time preceding the exposure to IR were sufficient to confer the radioresistant effect. Notorious among the changes brought by adipocytes was the significant increase of IL-6 expression in tumor cells, whose activity may well account for the observed tumor cell protection from IR toxicity. Indeed, our data confirmed the protective role of this cytokine as tumor cells incubated after irradiation with recombinant IL-6 exhibit an increased in Chk1 phosphorylation and a radioresistant phenotype, thus far recapitulating the effects observed in the presence of adipocytes. Our current study sheds light on a new role of tumor-surrounding adipocytes in fostering a radioresistant phenotype in breast tumors, a finding that might have important clinical implications in obese patients that frequently exhibit aggressive diseases.

  13. Radioresistance increase in polymers at high pressures. [. gamma. rays

    Energy Technology Data Exchange (ETDEWEB)

    Milinchuk, V; KIRJUKHIN, V; KLINSHPONT, E

    1977-06-01

    The effect was studied of very high pressures ranging within 100 and 2,700 MPa on the radioresistance of polytetrafluoroethylene, polypropylene and polyethylene in gamma irradiation. For experiments industrial polymers in the shape of blocks, films and fibers were used. It is shown that in easily breakable polymers, such as polytetrafluoroethylene and polypropylene, 1.3 to 2 times less free radicals are formed as a result of gamma irradiation and a pressure of 150 MPa than at normal pressure. The considerably reduced radiation-chemical formation of radicals and the destruction suppression by cross-linking in polymers is the evidence of the polymer radioresistance in irradiation at high pressures.

  14. Microbial radio-resistance of Salmonella Typhimurium in egg increases due to repetitive irradiation with electron beam

    International Nuclear Information System (INIS)

    Tesfai, Adiam T.; Beamer, Sarah K.; Matak, Kristen E.; Jaczynski, Jacek

    2011-01-01

    Ionizing radiation improves food safety. However, foodborne pathogens develop increased resistance in response to sub-lethal stresses such as heat, pH, antibiotics, etc. Therefore, it is hypothesized that foodborne pathogens may develop increased radio-resistance to electron beam (e-beam) radiation. The objective was to determine if D 10 -value for Salmonella Typhimurium in de-shelled raw egg (egg white and yolk mixed together) increases due to repetitive processing with e-beam at sub-lethal doses. Survivors were enumerated on non-selective (TSA) and selective (XLD) media. Survivors from the highest dose were isolated and used in subsequent e-beam cycle. This process was repeated four times for a total of five e-beam cycles. D 10 -values for S. Typhimurium enumerated on TSA and XLD following each e-beam cycle were calculated as inverse reciprocal of the slope of survivor curves. D 10 -values for the ATCC strain were 0.59±0.031 and 0.46±0.022 kGy on TSA and XLD, respectively. However, following the fifth e-beam cycle, the respective D 10 -values increased (P 0.05) to develop radio-resistance faster on selective media, likely due to facilitated selection of radio-resistant cells within microbial population following each e-beam cycle. For all five e-beam cycles, S. Typhimurium had higher (P 10 -values on non-selective media, indicating that sub-lethal injury followed by cellular repair and recovery are important for radio-resistance and inactivation of this microorganism. This study demonstrated that e-beam efficiently inactivates S. Typhimurium in raw egg; however, similar to other inactivation techniques and factors affecting microbial growth, S. Typhimurium develops increased radio-resistance if repetitively processed with e-beam at sub-lethal doses.

  15. Cell lysis and superoxide dismutase activities of highly radioresistant bacteria

    International Nuclear Information System (INIS)

    Yoshinaka, Taeko; Yano, Keiji; Yamaguchi, Hikoyuki

    1976-01-01

    The highly radioresistant bacterium, Arthrobacter radiotolerans, has been isolated from the radioactive hot spring of Misasa, and it does not sporulate, it is Gram-positive, and its color is pink to red. This bacterium shows the highest resistance to gamma-ray among Gram-positive resistants, but the lytic enzyme capable of lysing the cells of strong radioresistants and the surface structure of the cells are little known except those about Micrococcus radiodurans. The cells of the M. radiodurans can be lysed by Achramobacter lyticus enzyme, and electron microscopic observation and chemical analysis revealed the mutilayered surface structure of the cells consisting of an inner membrane, a mucopeptide wall layer and a very outer layer. The superoxide dismutase (SOD) activity of aerobic and anaerobic bacteria was studied, and the relatively high SOD activity of the M. radiodurans was found. The SOD function acts against the threat posed by the reactive superoxide radical being generated biologically, photochemically and radiochemically in the presence of molecular oxygen. In this paper, it is reported that the lytic enzyme No.2 obtained from Cytophaga sp., containing N-acetyl-muramyl-L-alanine amidase, peptidase and endopeptidase, and showing broad lytic spectra, was able to lyse the cells of A. radiotolerans and four radioresistant micrococci, and the radioresistant bacteria showed relatively high SOD activity except M. sp. 248. It is well known that superoxide anions are generated by aerobic irradiation, and are toxic to microbial cells. (Kako, I.)

  16. Cell lysis and superoxide dismutase activities of highly radioresistant bacteria

    Energy Technology Data Exchange (ETDEWEB)

    Yoshinaka, T; Yano, K; Yamaguchi, H [Tokyo Univ. (Japan). Faculty of Agriculture

    1976-01-01

    The highly radioresistant bacterium, Arthrobacter radiotolerans, has been isolated from the radioactive hot spring of Misasa, and it does not sporulate, it is Gram-positive, and its color is pink to red. This bacterium shows the highest resistance to gamma-ray among Gram-positive resistants, but the lytic enzyme capable of lysing the cells of strong radioresistants and the surface structure of the cells are little known except those about Micrococcus radiodurans. The cells of the M. radiodurans can be lysed by Achramobacter lyticus enzyme, and electron microscopic observation and chemical analysis revealed the mutilayered surface structure of the cells consisting of an inner membrane, a mucopeptide wall layer and a very outer layer. The superoxide dismutase (SOD) activity of aerobic and anaerobic bacteria was studied, and the relatively high SOD activity of the M. radiodurans was found. The SOD function acts against the threat posed by the reactive superoxide radical being generated biologically, photochemically and radiochemically in the presence of molecular oxygen. In this paper, it is reported that the lytic enzyme No.2 obtained from Cytophaga sp., containing N-acetyl-muramyl-L-alanine amidase, peptidase and endopeptidase, and showing broad lytic spectra, was able to lyse the cells of A. radiotolerans and four radioresistant micrococci, and the radioresistant bacteria showedrelatively high SOD activity except M. sp. 248. It is well known that superoxide anions are generated by aerobic irradiation, and are toxic to microbial cells.

  17. Metabolism of the chemo antibiotic combination sulphamethoxazol and trimethoprim by some radioresistant strains

    International Nuclear Information System (INIS)

    Zahiera, T.S.

    1990-01-01

    The radioresistant mutants B. Firmus, B. Laterosporus, B. Megaterium, M. Roseus and M. Luteus were tested microbiologically for their sensitivity to a drug consisting of the chemo antibiotic combination of sulphamethoxazole (SMZ) and trimethoprim (TMP) in a ratio of 20:1. All the studied mutant strains were found to be insensitive to this combination of antibiotics except the radioresistant mutant strain of M.roseus. The mechanism of the inactivation of both SMZ and TMP by the radioresistant mutants of B. Laterosporus, B. Firmus, and M.Luteus was studied. The drug was incubated with each of these mutants for different periods of time to study its degradation. High performance liquid chromatography and microbiological assay techniques were used to determine the activity and the pathway of the consumption of the drug after its incubation with these three mutants for time. The results indicated that the drug acts in a synergistic effect on all the studied mutants. Only a part of both molecules of SMZ and TMP was utilized by the studied mutant strains. The ratio of the left over of SMZ/TMP were found to be 6,6 and 8 after seven days incubation periods and 12, 7.5 and 19 after two weeks incubation periods with B. Laterosporus, B. Firmus, and M. Luteus mutants respectively. The microbial activity of the extracted drug for bacilli strains isolated from clean environment had not changed significantly due to incubation with the mutants, but it was decreased for M. Luteus strain. The drug inactivation by the studied mutant strains seemed to be due to decreased affinities to SMZ and TMP, and to formation of an altered 7,8 dihydropteroate synthetase and dihydrofolate reductase

  18. Discovery of the cancer stem cell related determinants of radioresistance

    International Nuclear Information System (INIS)

    Peitzsch, Claudia; Kurth, Ina; Kunz-Schughart, Leoni; Baumann, Michael; Dubrovska, Anna

    2013-01-01

    Tumors are known to be heterogeneous containing a dynamic mixture of phenotypically and functionally different tumor cells. The two concepts attempting to explain the origin of intratumor heterogeneity are the cancer stem cell hypothesis and the clonal evolution model. The stochastic model argues that tumors are biologically homogenous and all cancer cells within the tumor have equal ability to propagate the tumor growth depending on continuing mutations and selective pressure. By contrast, the stem cells model suggests that cancer heterogeneity is due to the hierarchy that originates from a small population of cancer stem cells (CSCs) which are biologically distinct from the bulk tumor and possesses self-renewal, tumorigenic and multilineage potential. Although these two hypotheses have been discussed for a long time as mutually exclusive explanations of tumor heterogeneity, they are easily reconciled serving as a driving force of cancer evolution and diversity. Recent discovery of the cancer cell plasticity and heterogeneity makes the CSC population a moving target that could be hard to track and eradicate. Understanding the signaling mechanisms regulating CSCs during the course of cancer treatment can be indispensable for the optimization of current treatment strategies

  19. Breast cancer stem cell-like cells generated during TGFβ-induced EMT are radioresistant.

    Science.gov (United States)

    Konge, Julie; Leteurtre, François; Goislard, Maud; Biard, Denis; Morel-Altmeyer, Sandrine; Vaurijoux, Aurélie; Gruel, Gaetan; Chevillard, Sylvie; Lebeau, Jérôme

    2018-05-04

    Failure of conventional antitumor therapy is commonly associated with cancer stem cells (CSCs), which are often defined as inherently resistant to radiation and chemotherapeutic agents. However, controversy about the mechanisms involved in the radiation response remains and the inherent intrinsic radioresistance of CSCs has also been questioned. These discrepancies observed in the literature are strongly associated with the cell models used. In order to clarify these contradictory observations, we studied the radiosensitivity of breast CSCs using purified CD24 -/low /CD44 + CSCs and their corresponding CD24 + /CD44 low non-stem cells. These cells were generated after induction of the epithelial-mesenchymal transition (EMT) by transforming growth factor β (TGFβ) in immortalized human mammary epithelial cells (HMLE). Consequently, these 2 cellular subpopulations have an identical genetic background, their differences being related exclusively to TGFβ-induced cell reprogramming. We showed that mesenchymal CD24 -/low /CD44 + CSCs are more resistant to radiation compared with CD24 + /CD44 low parental cells. Cell cycle distribution and free radical scavengers, but not DNA repair efficiency, appeared to be intrinsic determinants of cellular radiosensitivity. Finally, for the first time, we showed that reduced radiation-induced activation of the death receptor pathways (FasL, TRAIL and TNF-α) at the transcriptional level was a key causal event in the radioresistance of CD24 -/low / CD44+ cells acquired during EMT.

  20. Content of endogenous thiols and radioresistance of gemmating cells of Saccharomyces ellipsoideus and Saccharomyces cerevisiale yeasts

    International Nuclear Information System (INIS)

    Simonyan, N.V.; Avakyan, Ts.M.; Dzhanpoladyan, N.L.; Stepanyan, L.G.

    1983-01-01

    It has been shown that gemmating cells of ''wild type'' yeasts are more radioresistant and contain more endogenous thiols, than resting cells. Gemmating cells of Saccharomyces cerevisial yeasts, carrying the mutation rad 51, as to radioresistance and content of SH groups do not differ from resting cells. The results obtained testify to a connec-- tion between increased radioresistance of the yeast gemmating cells and increased content of endogenous thiols in them

  1. Induction of transient radioresistance in human erythrocytes

    International Nuclear Information System (INIS)

    Krokosz, Anita; Szweda-Lewandowska, Zofia

    2006-01-01

    Human erythrocytes suspended in an isotonic Na-phosphate buffer, pH 7.4 (hematocrit of 2%), were irradiated with γ-rays with single and split doses under air or N 2 O in order to determine the physicochemical changes caused by the dose inducing an increase in resistance to radiation-induced hemolysis. The obtained results showed that under the applied irradiation conditions, the dose of 0.4 kGy induced changes in erythrocytes, which were responsible for temporary resistance of erythrocytes to hemolysis. We concluded that the observed resistance is caused mainly by the structural changes in proteins

  2. Dietary enhancement of intestinal radioresistance during fractionated irradiation

    International Nuclear Information System (INIS)

    Pageau, R.; St-Pierre, C.

    1978-01-01

    Rats fed laboratory chow or elemental diet 3 were given fractions of 240 rads of 60 Co γ radiation abdominally (1200 rads/week) until all animals had died. Changes in appetite, body weight, and mortality were monitored as a function of the cumulative dose received. More radiation was needed in the diet-fed group to achieve both 0 and 100% mortality, a difference of 37% at the mean lethal dose level. Both groups developed similar progressive anorexia but the diet-fed animals lost weight more slowly. Data indicate that basic intestinal radioresistance is enhanced by feeding the elemental diet

  3. Recovery and radio-resistance in mice after external irradiation

    International Nuclear Information System (INIS)

    Le Guillou, S.

    1965-01-01

    The author presents a literature study concerning recovery from external irradiation and an analysis of experimental data (which appear to suggest the idea of a radio-resistance in animals), as well as the hypotheses put forward for explaining this phenomenon. The author then describes an experiment carried out on mice whose LD 50/30 days increased from 1005 to 1380 rads and for which it was shown that an increase occurs in the number of certain anti-bodies circulating after a low dose of γ irradiation. (author) [fr

  4. Isolation and identification of a novel radio-resistant strain

    International Nuclear Information System (INIS)

    Zhang Zhidong; Mao Jun; Wang Wei; Tang Qiyong; Shi Yuhu

    2008-01-01

    A novel radio-resistant strain named RL2 was studied polyphasically, which was isolated from the soils in the Gurban-Tunggut Desert, Xinjiang. The strain is Gam-positive, sphere-shaped and pink pigmented; The DNA (G+C) contents of RL2 is 71.62mo1%; The 16S rDNA genes of RL2 and D. radiodurans type strain DSM20539 shows a high level of similarity (97.2%). According to phenotypic characteristics and phylogenetic analysis, it can be suggested that the strain RL2 has been identified as Deinococcus. sp and it may be a novel species. (authors)

  5. Investigation of ionizing sublethal doses effects on endogenous radioresistance background

    International Nuclear Information System (INIS)

    Kudryashov, Yu.B.; Goncharenko, E.N.; Antonova, S.V.; Akhalaya, M.Ya.; Bajzhumanov, A.A.; Shestakova, S.V.

    1997-01-01

    Sublethal doses of X-radiation (0.5 Gy and 1 Gy) caused the alterations in levels of main components of endogenous radioresistance background in rat tissues. There were demonstrated the decrease of serotonin content in stomach mocosa and spleen, adrenalin, noradrenalin and corticosteroids contents in adrenal glands, nonprotein thiols content in spleen and the increase of lipid peroxide level in serum on the 3-14 days after irradiation. The recovery of the investigated parameters was occurred to the 21 day after exposure. (author)

  6. Microbial radio-resistance of Salmonella Typhimurium in egg increases due to repetitive irradiation with electron beam

    Energy Technology Data Exchange (ETDEWEB)

    Tesfai, Adiam T.; Beamer, Sarah K.; Matak, Kristen E. [West Virginia University, Division of Animal and Nutritional Sciences, PO Box 6108, Morgantown, WV 26508 (United States); Jaczynski, Jacek, E-mail: Jacek.Jaczynski@mail.wvu.ed [West Virginia University, Division of Animal and Nutritional Sciences, PO Box 6108, Morgantown, WV 26508 (United States)

    2011-04-15

    Ionizing radiation improves food safety. However, foodborne pathogens develop increased resistance in response to sub-lethal stresses such as heat, pH, antibiotics, etc. Therefore, it is hypothesized that foodborne pathogens may develop increased radio-resistance to electron beam (e-beam) radiation. The objective was to determine if D{sub 10}-value for Salmonella Typhimurium in de-shelled raw egg (egg white and yolk mixed together) increases due to repetitive processing with e-beam at sub-lethal doses. Survivors were enumerated on non-selective (TSA) and selective (XLD) media. Survivors from the highest dose were isolated and used in subsequent e-beam cycle. This process was repeated four times for a total of five e-beam cycles. D{sub 10}-values for S. Typhimurium enumerated on TSA and XLD following each e-beam cycle were calculated as inverse reciprocal of the slope of survivor curves. D{sub 10}-values for the ATCC strain were 0.59{+-}0.031 and 0.46{+-}0.022 kGy on TSA and XLD, respectively. However, following the fifth e-beam cycle, the respective D{sub 10}-values increased (P<0.05) to 0.69{+-}0.026 and 0.61{+-}0.029 kGy, respectively. S. Typhimurium showed a trend (P>0.05) to develop radio-resistance faster on selective media, likely due to facilitated selection of radio-resistant cells within microbial population following each e-beam cycle. For all five e-beam cycles, S. Typhimurium had higher (P<0.05) D{sub 10}-values on non-selective media, indicating that sub-lethal injury followed by cellular repair and recovery are important for radio-resistance and inactivation of this microorganism. This study demonstrated that e-beam efficiently inactivates S. Typhimurium in raw egg; however, similar to other inactivation techniques and factors affecting microbial growth, S. Typhimurium develops increased radio-resistance if repetitively processed with e-beam at sub-lethal doses.

  7. Canonical autophagy does not contribute to cellular radioresistance

    International Nuclear Information System (INIS)

    Schaaf, Marco B.E.; Jutten, Barry; Keulers, Tom G.; Savelkouls, Kim G.M.; Peeters, Hanneke J.M.; Beucken, Twan van den; Schooten, Frederik-Jan van; Godschalk, Roger W.; Vooijs, Marc; Rouschop, Kasper M.A.

    2015-01-01

    Background: (Pre)clinical studies indicate that autophagy inhibition increases response to anti-cancer therapies. Although promising, due to contradicting reports, it remains unclear if radiation therapy changes autophagy activity and if autophagy inhibition changes the cellular intrinsic radiosensitivity. Discrepancies may result from different assays and models through off-target effects and influencing other signaling routes. In this study, we directly compared the effects of genetic and pharmacological inhibition of autophagy after irradiation in human cancer cell lines. Materials and methods: Changes in autophagy activity after ionizing radiation (IR) were assessed by flux analysis in eight cell lines. Clonogenic survival, DNA damage (COMET-assay) and H2AX phosphorylation were assessed after chloroquine or 3-methyladenine pretreatment and after ATG7 or LC3b knockdown. Results: IR failed to induce autophagy and chloroquine failed to change intrinsic radiosensitivity of cells. Interestingly, 3-methyladenine and ATG7- or LC3b-deficiency sensitized cancer cells to irradiation. Surprisingly, the radiosensitizing effect of 3-methyladenine was also observed in ATG7 and LC3b deficient cells and was associated with attenuated γ-H2AX formation and DNA damage repair. Conclusion: Our data demonstrate that the anti-tumor effects of chloroquine are independent of changes in intrinsic radioresistance. Furthermore, ATG7 and LC3b support radioresistance independent of canonical autophagy that involves lysosomal degradation

  8. Radiosensitivity of antibody responses and radioresistant secondary tetanus antitoxin responses

    International Nuclear Information System (INIS)

    Stoner, R.; Terres, G.; Cottier, H.; Hess, M.

    1976-01-01

    Primary tetanus antitoxin responses were increasingly repressed in mice when gamma radiation doses of 100 to 400 rads were delivered by whole-body exposure prior to immunization with fluid tetanus toxoid (FTT). Nearly normal secondary antitoxin responses were obtained in mice exposed to 600 rads of gamma radiation 4 days after secondary antigenic stimulation with FTT. A rapid transition from radiosensitivity of the antibody-forming system on days 1 to 3 was followed by relative radioresistance on day 4 after the booster injection of toxoid. Studies on lymphoid cellular kinetics in popliteal lymph nodes after injection of 3 H--thymidine ( 3 H--TdR) and incorporation of 3 H--L-histidine into circulating antitoxin were carried out. Analysis of tritium radioactivity in antigen--antibody precipitates of serums 2 hr after injection of the labeled amino acid revealed maximum incorporation into antibody around day 7 after the booster in nonirradiated controls and about day 12, i.e., 8 days after irradiation, in experimental mice. The shift from radiosensitivity to relative radioresistance was attributed to a marked peak of plasma-cell proliferation in the medulla of lymph nodes on day 3. Many medullary plasma cells survived and continued to proliferate after exposure to radiation. Germinal centers were destroyed by radiation within 1 day. Since antibody formation continued after exposure to radiation and after the loss of germinal centers, this supports the view that germinal-center cells were involved more in the generation of memory cells than in antibody synthesis

  9. Role of certain cellular composition in radio-resistant fungi

    International Nuclear Information System (INIS)

    Shahin, A.A.M.; Hammad, A.A.I.; Hazaa, M.M.; Swelim, M.A.; Mohamed, Y.A.

    2007-01-01

    Fifty three fungal isolates of genera Curvularia, Alternaria and Fusarium were isolated from different sources included crops, vegetables, fruits in addition to bread, chicken feed soil and air. Five isolates were selected from each genus according to the difference in the morphological characters and its source. The fifteen isolates were exposed to increasing doses of gamma rays from 0.5 to 10.0 I 10 values when irradiated in saline solution were found to be 1.92,1.25, 1.47,0.47,1.31 and 0.70 respectively while their D 10 values were 2.25, 1.56, 1.70, 1.30, 1.83 and 1.23 as the irradiation process was done in their natural sources. The values of total protein, total lipids and total nucleic acids either RNA or DNA were relatively higher in radio-resistant strains than sensitive ones. Amino acids containing sulfur (cysteine, methionine) or double bonds (histidine) and the percentage of unsaturated fatty acids were also higher in resistant strains than the sensitive ones. Exposing the six selected strains to dose level 4 kGy obviously decreased each of total protein, total amino acids and total nucleic acids especially DNA and the values of decreases were found to be higher in sensitive than the resistant strains. Dose level 12.5 kGy was quiet enough to eliminate the radioresistant fungi from the contaminated food whatever the level of contamination is

  10. Evaluation of the role of genetic factors in human radioresistance

    International Nuclear Information System (INIS)

    Telnov, Vitaliy I.; Sotnik, Natalie V.

    2002-01-01

    This study was focused on evaluation of the role of genetic factors in development of chronic radiation sickness (CRS) due to occupational exposure to external γ -rays. This study was based on results of molecular-genetic studies for 985 nuclear workers of the Mayak Production Association. CRS occurrence was related to the genetic haptoglobin (Hp) system among a number of studied genetic markers. Excess risk of CRS was revealed at similar exposure doses for individuals-carriers of Hp 2-2 (1.96) versus lower risks for carriers of Hp 1-1 and 2-1 (0.64). The contribution of genetic factors to CRS development was implemented in a rather narrow dose range, i.e. it was of a relative nature. A scheme of the relationship of affecting factor and differences in genetic radioresistance was presented in terms of deterministic effects. The obtained data did not confirm the idea that A-bomb survivors were more radioresistant, thus being not representative for radiation risk estimation

  11. Impairing the radioresistance of cancer cells by hydrogenated nanodiamonds.

    Science.gov (United States)

    Grall, Romain; Girard, Hugues; Saad, Lina; Petit, Tristan; Gesset, Céline; Combis-Schlumberger, Mathilde; Paget, Vincent; Delic, Jozo; Arnault, Jean-Charles; Chevillard, Sylvie

    2015-08-01

    Hydrogenated nanodiamonds (H-NDs) exhibit a negative electron affinity that confers a high reactivity with oxygen species and a positive charge in aqueous solutions. It allows electron emission from H-NDs following irradiation by photons and in consequence may enhance the effects of radiation on cancer cells. By using three human radioresistant cancer cell lines, we showed a potentialization of cytotoxicity after a co-exposure to H-NDs and irradiation; an event occurring through the induction of DNA damage and reactive oxygen species. This occurred together with a decrease in cell impedance, the activation of G1/S, an unlocking of G2 cell cycle check-points and early low cell death rate. At later stage of exposure, persistent increases in heterochromatinization, large γ-H2AX foci and β-galactosidase activity were detected providing evidence of cells' entrance into senescence. Similar potentialization was observed with neocarzinostatin (NCS), a radiomimetic drug. This original finding underlines a wide clinical potential of H-NDs to intensify radiation effects on radio-resistant cancer cells. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. Targeting DNA repair with PNKP inhibition sensitizes radioresistant prostate cancer cells to high LET radiation.

    Directory of Open Access Journals (Sweden)

    Pallavi Srivastava

    Full Text Available High linear energy transfer (LET radiation or heavy ion such as carbon ion radiation is used as a method for advanced radiotherapy in the treatment of cancer. It has many advantages over the conventional photon based radiotherapy using Co-60 gamma or high energy X-rays from a Linear Accelerator. However, charged particle therapy is very costly. One way to reduce the cost as well as irradiation effects on normal cells is to reduce the dose of radiation by enhancing the radiation sensitivity through the use of a radiomodulator. PNKP (polynucleotide kinase/phosphatase is an enzyme which plays important role in the non-homologous end joining (NHEJ DNA repair pathway. It is expected that inhibition of PNKP activity may enhance the efficacy of the charged particle irradiation in the radioresistant prostate cancer cell line PC-3. To test this hypothesis, we investigated cellular radiosensitivity by clonogenic cell survival assay in PC-3 cells.12Carbon ion beam of62 MeVenergy (equivalent 5.16 MeV/nucleon and with an entrance LET of 287 kev/μm was used for the present study. Apoptotic parameters such as nuclear fragmentation and caspase-3 activity were measured by DAPI staining, nuclear ladder assay and colorimetric caspase-3method. Cell cycle arrest was determined by FACS analysis. Cell death was enhanced when carbon ion irradiation is combined with PNKPi (PNKP inhibitor to treat cells as compared to that seen for PNKPi untreated cells. A low concentration (10μM of PNKPi effectively radiosensitized the PC-3 cells in terms of reduction of dose in achieving the same survival fraction. PC-3 cells underwent significant apoptosis and cell cycle arrest too was enhanced at G2/M phase when carbon ion irradiation was combined with PNKPi treatment. Our findings suggest that combined treatment of carbon ion irradiation and PNKP inhibition could enhance cellular radiosensitivity in a radioresistant prostate cancer cell line PC-3. The synergistic effect of PNKPi

  13. AKT-mediated enhanced aerobic glycolysis causes acquired radioresistance by human tumor cells

    International Nuclear Information System (INIS)

    Shimura, Tsutomu; Noma, Naoto; Sano, Yui; Ochiai, Yasushi; Oikawa, Toshiyuki; Fukumoto, Manabu; Kunugita, Naoki

    2014-01-01

    Background and purpose: Cellular radioresistance is a major impediment to effective radiotherapy. Here, we demonstrated that long-term exposure to fractionated radiation conferred acquired radioresistance to tumor cells due to AKT-mediated enhanced aerobic glycolysis. Material and methods: Two human tumor cell lines with acquired radioresistance were established by long-term exposure to fractionated radiation with 0.5 Gy of X-rays. Glucose uptake was inhibited using 2-deoxy-D-glucose, a non-metabolizable glucose analog. Aerobic glycolysis was assessed by measuring lactate concentrations. Cells were then used for assays of ROS generation, survival, and cell death as assessed by annexin V staining. Results: Enhanced aerobic glycolysis was shown by increased glucose transporter Glut1 expression and a high lactate production rate in acquired radioresistant cells compared with parental cells. Inhibiting the AKT pathway using the AKT inhibitor API-2 abrogated these phenomena. Moreover, we found that inhibiting glycolysis with 2-deoxy-D-glucose suppressed acquired tumor cell radioresistance. Conclusions: Long-term fractionated radiation confers acquired radioresistance to tumor cells by AKT-mediated alterations in their glucose metabolic pathway. Thus, tumor cell metabolic pathway is an attractive target to eliminate radioresistant cells and improve radiotherapy efficacy

  14. Molecular biological studies on the human radioresistance and drug resistance

    International Nuclear Information System (INIS)

    Kim, Chang Min; Hong, Weon Seon

    1992-04-01

    We irradiated the MKN45 and PC14 cell lines with 500 rads and also established the adriamycin-resistant and cis-platinum resistant cell line. The genomic DNA and total RNA were extracted and subjected to the Southern and Northern analysis using various probes including heat shock protein 70, MDR1, fos, TGFb etc. The mRNA transcript was increased 1 hour after the irradiation and sustained during the 48 hours and returned to the level of pre-irradiation. No significant change was observed with the drug resistant cell lines at the level of gene dosage. We suggest that the marked increase of the hsp70 transcript is very important finding and is believed to be a good candidate for the modulation of the cellular response to irradiation and the radioresistance. (Author)

  15. A role for survivin in radioresistance of pancreatic cancer cells

    International Nuclear Information System (INIS)

    Asanuma, Koichi; Kobayashi, Daisuke; Furuya, Daisuke; Tsuji, Naoki; Yagihashi, Atsuhito; Watanabe, Naoki

    2002-01-01

    Using gene-transduced pancreatic cancer cells, we examined whether survivin expression is directly involved in regulation of radiosensitivity. Ordinarily radiosensitive MIAPaCa-2 cells transduced with wild-type survivin gene (MS cells) proliferated more rapidly than cells transduced with control vector. MS cells were significantly less radiosensitive than control vector-transduced cells. Radiation-induced activity of caspase-3, but not caspase-7, was significantly inhibited in MS cells. On the other hand, transduction of a dominant-negative mutant survivin gene into radioresistant PANC-1 cells augmented radiosensitivity. Further, the radiation-induced increase in caspase-3 activity was enhanced, indicating that survivin function was truly inhibited. These results indicate that survivin expression directly down-regulates radiosensitivity. (author)

  16. Superoxide dismutase in radioresistant PC-3 human prostate carcinoma cells

    International Nuclear Information System (INIS)

    Prokopovic, J.; Adzic M; Niciforovic, A.; Vucic, V.; Zaric, B.; Radojcic, M. B.

    2006-01-01

    The molecular mechanism of gamma-ionizing radiation (IR) resistance of human prostate cancer cells PC-3 is not known. Since low-LET-IR effects are primarily achieved through generation of reactive oxygen species (ROS), IR-induced expression of ROS-metabolizing antioxidant enzymes, Mn- and CuZn-superoxide dismutase (Mn- and CuZnSOD) and catalase (CAT), and their upstream regulator transcription factor NFκB was followed. Significant elevation of both SODs was found in cells irradiated with 10- and 20 Gy, while CAT and NFκB expression was unchanged. Since, such conditions lead to accumulation of H 2 O 2 , it is concluded that radioresistance of PC-3 cells may emerge from positive feed-forward vicious circle established between H 2 O 2 activation of NFκB and elevated MnSOD activity. (author)

  17. Selection of radioresistant tumor cells and presence of ALDH1 activity in vitro

    International Nuclear Information System (INIS)

    Mihatsch, Julia; Toulany, Mahmoud; Bareiss, Petra M.; Grimm, Sabrina; Lengerke, Claudia; Kehlbach, Rainer; Rodemann, H. Peter

    2011-01-01

    Background: Tumor resistance to radiotherapy has been hypothesized to be mediated by a tumor subpopulation, called cancer stem cells (CSCs). Based on the proposed function of CSCs in radioresistance, we explored the cancer stem cell properties of cells selected for radioresistance phenotype. Materials and methods: A549 and SK-BR-3 cells were radioselected with four single doses of 4 or 3 Gy in intervals of 10-12 days and used for colony formation assay and γ-H2AX foci formation assay. Expression of putative stem cell markers, i.e. Sox2, Oct4, ALDH1, and CD133 were analyzed using Western blotting. A549 and SK-BR-3 cells sorted based on their ALDH1 activity were analyzed in clonogenic survival assays. Results: Radioselected A549 and SK-BR-3 cells (A549-R, SK-BR-3-R) showed increased radioresistance and A549-R cells presented enhanced repair of DNA-double strand breaks. PI3K inhibition significantly reduced radioresistance of A549-R cells. Cell line specific differences in the expression of the putative CSC markers Sox2 and Oct4 were observed when parental and radioselected cells were compared but could not be directly correlated to the radioresistant phenotype. However, enzyme activity of the putative stem cell marker ALDH1 showed a correlation to radioresistance. Conclusions: Subpopulations of pooled radioresistant colonies, selected by various radiation exposures were analyzed for the presence of putative stem cell markers. Although the pattern of Sox2, Oct4, and CD133 expression was not generally associated with radioresistance, presence of ALDH1 seems to be indicative for subpopulations with increased radioresistance.

  18. Demonstration and suppression of a radioresistant host-versus-graft reaction

    International Nuclear Information System (INIS)

    Thierfelder, S.; Roessler, R. v.; Ruppelt, W.

    1975-01-01

    The possibilities of suppressing and measuring a radioresistant host-versus-graft reaction are described. According to the authors, the host-versus-graft immune reaction may outlast whole-body irradiation at high doses. (BSC/AK) [de

  19. Comparative radioresistance of chronically irradiated populations of Arabidopsis thaliana (L.) Heynh

    International Nuclear Information System (INIS)

    Dineva, S.B.; Abramov, V.I.; Shevchenko, V.A.

    1994-01-01

    The radioresistance of seeds of populations of Arabidopsis thaliana (L.) Heynh. growing for 5 years in the regions with different levels of radioactive contamination within 30 km zone of Chernobyl NPP was studied. The analysis of comparative radiosensitivity by root test was performed. It has been shown that plants from arabidopsis population growing under chronic irradiation did not gain an increased radioresistance. The data obtained shown that they are more radiosensitive

  20. Modification of γ-irradiation damaging effect on the seeds of radiosensitive and radioresistant plants

    International Nuclear Information System (INIS)

    Kaplan, I.S.; Tikhomirov, F.A.; Khvostova, V.V.; AN SSSR, Novosibirsk. Inst. Tsitologii i Genetiki)

    1975-01-01

    Low and high temperature treatment of seeds during irradiation has shown to result in a decrease of the general deleterious effect of radiation in both relatively radiosensitive (bean) and radioresistant (flax, mustard) species. The protective effect of the treatment is supposed to be due to its influence on short-half-life radicals and this is supportted by experiments with storage of irradiated seeds. The treatment allows to obtain high mutation frequencies in both radiosensitive and radioresistant plants

  1. Increase of corneal epithelium cell radioresistance during regeneration

    International Nuclear Information System (INIS)

    Popova, M.F.; Bulyakova, N.V.; Azarova, V.S.

    1985-01-01

    A comparative study of the radiosensitivity of the normal and regenerating cornea epithelium of C 57 Bl mice was performed on the cellular level, the duration of the cell cycle being taken into account. Criteria of radiation injuries were the number of chromosome aberrations, mitotic index and duration of mitotic block. The anterior part of the head was irradiated singly with 1.75, 3.5 or 7.0 Gy and also repeatedly 3.5 + 3.5 at a 24-hours interval. The corneas were fixed 2, 4, 6, 12, 24, 48, 72 and 96 hours after irradiation. In all cases of irradiated mice the regenerating epithelium showed a shorter mitotic block and significantly lower cytogenetic injury as compared with the controls. Effects of fractionated irradiation were only shown in the regenerating epithelium. The results obtained indicate that regenerating epithelium cells of the cornea are significantly more radioresistant than normal epithelium due to activation of post-radiation recovery, and also, possibly, due to an increase in the content of endogenous radioprotectors. (author)

  2. Radiation-induced-radioresistance: mechanisms and modification radioprotection

    International Nuclear Information System (INIS)

    Bala, Madhu

    2005-01-01

    Full text: The term radiation-induced-radioresistance (RIR) has been chosen to explain a particular class of resistance against lethal doses of radiation, which is transient and is induced by pre-exposure to low doses of radiation. This is a genetically governed phenomenon and is different from adaptation which in one of its several senses, refers to evolutionary transformation into new behavioural patterns. RIR is understood to be an evolutionarily conserved fundamental cellular defense mechanism. Small doses of radiation acting as stress stimuli evoke a concerted action of molecular pathways which help the organism to cope-up with the genotoxic effects of lethal doses of radiation given subsequently. Such molecular pathways are a complex interplay of genetic and biochemical entities and are increasingly becoming the focus of research world over. Most of our information on this subject has been gathered from prokaryotes, simpler eukaryotes, human cells and the epidemiological studies. A number of genes such as GADD 45, CDKN1A, PBP74, DIR1, DDR have been reported by to participate in RIR. However, till date, the mechanism of RIR remain poorly understood. In this deliberation some of our findings on mechanisms of RIR will be presented. Further, modification of RIR by a metabolic modifier, presently under clinical investigations for tumor radiotherapy, will also be presented

  3. Inactivation of carbenicillin by some radioresistant mutant strains

    International Nuclear Information System (INIS)

    Zahiera, T.S.; Mahmoud, M.I.; Bashandy, A.A.

    1990-01-01

    Sensitivity test of five bacterial species to carbenicillin was performed microbiologically. The bacterial species were previously isolated from high level radiation environment. All the studied species could either highly decrease the antibiotic activity or even inactivate it completely. Detailed study of the inactivation of carbenicillin by the radioresistant mutant strains B. Laterosporus, B. firmus and M. roseus was performed, in the present study. Using high performace liquid chromatography technique. The gram-positive m. roseus mutant strain seemed to be the most active mutant in degrading the antibiotic. The left over of the antibiotic attained a value of 9% of the original amount after 14 day incubation of the antibiotic with this mutant strain, while the value of the left over reached 36% and 32% after the same period of incubation with the mutants B. laterosporus and B. firmus respectively. In the case of bacillus species, the degradation of the antibiotic started at the same moment when it was added to the bacterial cultures. This fact may indicate that the inactivation of the studied antibiotic by these bacillus species was due to extracellular enzymes extracted rapidly in the surrounding medium. In the case of M. roseus the inactivation process started later. after the addition of the antibiotic to the mutant culture

  4. Cytogenetic Effects of Low Dose Radiation in Mammalian Cells Analysis of the Phenomenon Hypersensitivity and Induced Radioresistence

    CERN Document Server

    Shmakova, N L; Nasonova, E A; Krasavin, E A; Rsjanina, A V

    2001-01-01

    The induction of cytogenetic damage after irradiation of chinese hamster cells and human melanoma cells within dose range 1-200 cGy was studied. The anaphase and metaphase analysis of chromosome damage and micronuclei test were applied. The hypersensitivity (HRS) at doses below 20 cGy and the increased radioresistence at higher doses (IR) were shown with all cytogenetic criteria for both cell lines. The phenomenon of HRS/IR was reproduced in synchronic as well as in asynchronic population of chinese hamster cells. This fact shows that HRS was caused by high radiosensitivity of all cells and can not be explained by any differential sensitivity of cells in different phases of the cell cycle. So it was supposed that the increasing radioresistence is determined by the inclusion of the inducible repair processes in all cells. This conclusion agress with the fact that there was no evidence of HRS on dose-effect curves and that some part of pre-existent damage was repaired after preliminary irradiation with low dose...

  5. Proteomic and transcriptomic profiling of in vitro established radiation resistant oral cancer cells for identification of radioresistance related biomarkers

    International Nuclear Information System (INIS)

    Mohd Yasser; Pawar, Sagar; Teni, Tanuja

    2016-01-01

    Radiotherapy is an integral part of oral cancer treatment, either alone or in combination with surgery. But, during radiotherapy, oral tumours of a subset of patients develop radioresistance that creates major obstruction towards its efficacy. The aim of our study was to establish radioresistant cell lines from different oral subsites using clinically admissible low dose radiation and profile them by proteomic and transcriptomic approaches to identify proteins associated with radioresistance in oral cancer

  6. Regulation of radiation-induced protein kinase Cδ activation in radiation-induced apoptosis differs between radiosensitive and radioresistant mouse thymic lymphoma cell lines

    International Nuclear Information System (INIS)

    Nakajima, Tetsuo; Yukawa, Osami; Tsuji, Hideo; Ohyama, Harumi; Wang, Bing; Tatsumi, Kouichi; Hayata, Isamu; Hama-Inaba, Hiroko

    2006-01-01

    Protein kinase Cδ (PKCδ) has an important role in radiation-induced apoptosis. The expression and function of PKCδ in radiation-induced apoptosis were assessed in a radiation-sensitive mouse thymic lymphoma cell line, 3SBH5, and its radioresistant variant, XR223. Rottlerin, a PKCδ-specific inhibitor, completely abolished radiation-induced apoptosis in 3SBH5. Radiation-induced PKCδ activation correlated with the degradation of PKCδ, indicating that PKCδ activation through degradation is involved in radiation-induced apoptosis in radiosensitive 3SBH5. In radioresistant XR223, radiation-induced PKCδ activation was lower than that in radiosensitive 3SBH5. Cytosol PKCδ levels in 3SBH5 decreased markedly after irradiation, while those in XR223 did not. There was no apparent change after irradiation in the membrane fractions of either cell type. In addition, basal cytosol PKCδ levels in XR223 were higher than those in 3SBH5. These results suggest that the radioresistance in XR223 to radiation-induced apoptosis is due to a difference in the regulation of radiation-induced PKCδ activation compared to that of 3SBH5. On the other hand, Atm -/- mouse thymic lymphoma cells were more radioresistant to radiation-induced apoptosis than wild-type mouse thymic lymphoma cells. Irradiated wild-type cells, but not Atm -/- cells, had decreased PKCδ levels, indicating that the Atm protein is involved in radiation-induced apoptosis through the induction of PKCδ degradation. The decreased Atm protein levels induced by treatment with Atm small interfering RNA had no effect on radiation-induced apoptosis in 3SBH5 cells. These results suggest that the regulation of radiation-induced PKCδ activation, which is distinct from the Atm-mediated cascade, determines radiation sensitivity in radiosensitive 3SBH5 cells

  7. Glioblastoma Stem Cells Microenvironment: The Paracrine Roles of the Niche in Drug and Radioresistance

    Directory of Open Access Journals (Sweden)

    Alessia Fidoamore

    2016-01-01

    Full Text Available Among all solid tumors, the high-grade glioma appears to be the most vascularized one. In fact, “microvascular hyperplasia” is a hallmark of GBM. An altered vascular network determines irregular blood flow, so that tumor cells spread rapidly beyond the diffusion distance of oxygen in the tissue, with the consequent formation of hypoxic or anoxic areas, where the bulk of glioblastoma stem cells (GSCs reside. The response to this event is the induction of angiogenesis, a process mediated by hypoxia inducible factors. However, this new capillary network is not efficient in maintaining a proper oxygen supply to the tumor mass, thereby causing an oxygen gradient within the neoplastic zone. This microenvironment helps GSCs to remain in a “quiescent” state preserving their potential to proliferate and differentiate, thus protecting them by the effects of chemo- and radiotherapy. Recent evidences suggest that responses of glioblastoma to standard therapies are determined by the microenvironment of the niche, where the GSCs reside, allowing a variety of mechanisms that contribute to the chemo- and radioresistance, by preserving GSCs. It is, therefore, crucial to investigate the components/factors of the niche in order to formulate new adjuvant therapies rendering more efficiently the gold standard therapies for this neoplasm.

  8. Detection of Quiescent Radioresistant Epithelial Progenitors in the Adult Thymus

    Directory of Open Access Journals (Sweden)

    Maude Dumont-Lagacé

    2017-12-01

    Full Text Available Thymic aging precedes that of other organs and is initiated by the gradual loss of thymic epithelial cells (TECs. Based on in vitro culture and transplantation assays, recent studies have reported on the presence of thymic epithelial progenitor cells (TEPCs in young adult mice. However, the physiological role and properties of TEPC populations reported to date remain unclear. Using an in vivo label-retention assay, we previously identified a population of quiescent but non-senescent TECs. The goals of this study were therefore (i to evaluate the contribution of these quiescent TECs to thymic regeneration following irradiation-induced acute thymic injury and (ii to characterize their phenotypic and molecular profiles using flow cytometry, immunohistology, and transcriptome sequencing. We report that while UEA1+ cells cycle the most in steady state, they are greatly affected by irradiation, leading to cell loss and proliferative arrest following acute thymic involution. On the opposite, the UEA1– subset of quiescent TECs is radioresistant and proliferate in situ following acute thymic involution, thereby contributing to thymic regeneration in 28- to 30-week-old mice. UEA1– quiescent TECs display an undifferentiated phenotype (co-expression of K8 and K5 cytokeratins and express high levels of genes that regulate stem cell activity in different tissues (e.g., Podxl and Ptprz1. In addition, two features suggest that UEA1– quiescent TECs occupy discrete stromal niches: (i their preferential location in clusters adjacent to the cortico-medullary junction and (ii their high expression of genes involved in cross talk with mesenchymal cells. The ability of UEA1– quiescent TECs to participate to TEC regeneration qualifies them as in vivo progenitor cells particularly relevant in the context of regeneration following acute thymic injury.

  9. Radioresistance of populations of bank voles Clethrionomys glareolus in radionuclide-contaminated areas

    International Nuclear Information System (INIS)

    Il'enko, A.I.; Krapivko, T.P.

    1994-01-01

    Contamination of extended territories with radionuclides renders the monitoring of natural populations in their habitats an important work to be done in order to determine the directions of evolution caused by long-term exposure to ionizing radiation. In view of this, many years of field and experimental radioecological studies were devoted to animal populations that inhabit the territories contaminated with 137 Cs after the Chernobyl Power Plant disaster. Special emphasis was placed on the investigation of the time course of radiosensitivity of mammalian populations over several generations as a general index of adaptive processes developing in an area with an elevated radiation background. The authors monitored the population of the European bank vole, a species known for its high spontaneous resistance to radiation. In optimal environmental conditions, it has LD 50/30 = 9.7 Gy. The reaction of bank vole populations to radioactive contamination of their environment primarily increases the rate of variation of sensitivity to ionizing radiation. This results in a continuous increase in the radioresistance of the populations to a certains table level. The findings suggest that adaptive processes occur in natural mammalian populations subjected to chronic ionizing irradiation

  10. Stable radioresistance in ataxia-telangiectasia cells containing DNA from normal human cells

    International Nuclear Information System (INIS)

    Kapp, L.N.; Painter, R.B.

    1989-01-01

    SV40-transformed ataxia-telangiectasia (AT) cells were transfected with a cosmid containing a normal human DNA library and selectable marker, the neo gene, which endows successfully transformed mammalian cells with resistance to the antibiotic G418. Cells from this line were irradiated with 50 Gy of X-rays and fused with non-transfected AT cells. Among the G418-resistant colonies recovered was one stably resistant to radiation. Resistance to ionizing radiation of both primary transfectant line and its fusion derivative was intermediate between that of AT cells and normal cells, as assayed by colony-forming ability and measurement of radiation-induced G 2 chromatic aberrations; both cell lines retained AT-like radioresistant DNA synthesis. Results suggest that, because radioresistance in transfected cells was not as great as in normal human cells, two hallmarks of AT, radiosensitivity and radioresistant DNA synthesis, may still be the result of a single defective AT gene. (author)

  11. Expressed sequence tags of differential genes in the radioresistant mice and their parental mice

    International Nuclear Information System (INIS)

    Wang Qin; Yue Jingyin; Li Jin; Song Li; Liu Qiang; Mu Chuanjie; Wu Hongying

    2009-01-01

    Objective: To explore radioresistance correlative genes in IRM-2 inbred mouse. Methods: The total RNA was extracted from spleen cells of IRM-2 and their parent 615 and ICR/JCL mouse. The mRNA differential display technique was used to analyze gene expression differences. Each differential bands were amplified by PCR, cloned and sequenced. Results: There were 75 differential expression bands appearing in IRM-2 mouse but not in 615 and ICR/JCL mouse. Fifty-two pieces of cDNA sequences were got by sequencing. Twenty-one expressed sequence tags (EST) that were not the same as known mice genes were found and registered by comparing with GenBank database. Conclusion: Twenty-one EST denote that radioresistance correlative genes may be in IRM-2 mouse, which have laid a foundation for isolating and identifying radioresistance correlative genes in further study. (authors)

  12. No impact on P-gp level in radio-resistant Mcf-7 cells

    International Nuclear Information System (INIS)

    Madhu, L.N.; Rao, Shama; Sarojini, B.K.

    2016-01-01

    Cancer has become the leading cause of human death worldwide. One possible cause for therapeutic failure is that residual tumor cells are reminiscent of stem cells, which ultimately give rise to secondary tumors or distant metastasis. The property of resistance to radiation therapy or chemotherapy might be the major clinical criterion to characterize 'cancer stem cells (CSCs)'. In the process of radiotherapy, the radiosensitive cancer will become a radioresistant one. Such radio-resistance cells might also show the characters of multi drug resistance (MRD) properties which may affect the chemotherapy process. The present study was carried out to know the expression level of P-gp, a MRD protein in radioresistance breast cancer cells. The study conducted by exposing the MCF-7 cells to 4Gy of gamma radiation

  13. Impact of anthropogenic forest contamination on radioresistance of woody plant seed

    International Nuclear Information System (INIS)

    Yushkov, P.I.

    2004-01-01

    Radioresistance of seeds of bay willow (Salix pentandra L.) and great sallow willow (Salix caprea L.) from forests chronically affected and non-affected by acidic (SO 2 , NO x , HF, etc.) industries has been studied and compared. Bay willow seeds of 6 harvests showed no difference in radioresistance. However, seeds of both species manifested strong synchronous variability in resistance to preplant exposure. Also, no influence was observed of mother plant gas content on great sallow willow seeds of different harvests. Data obtained confirm similar results of previous studies conducted by the author (1987) to identify the impact of plant gas content on radioresistance of seeds and seedlings of pine (Pinus sylvestris L.) and birch (Betula verrucosa Erh.). (author)

  14. Up-regulation of integrin β3 in radioresistant pancreatic cancer impairs adenovirus-mediated gene therapy

    International Nuclear Information System (INIS)

    Egami, Takuya; Ohuchida, Kenoki; Yasui, Takaharu; Onimaru, Manabu; Toma, Hiroki; Sato, Norihiro; Tanaka, Masao; Mizumoto, Kazuhiro; Matsumoto, Kunio

    2009-01-01

    Adenovirus-mediated gene therapy is a promising approach for the treatment of pancreatic cancer. We previously reported that radiation enhanced adenovirus-mediated gene expression in pancreatic cancer, suggesting that adenoviral gene therapy might be more effective in radioresistant pancreatic cancer cells. In the present study, we compared the transduction efficiency of adenovirus-delivered genes in radiosensitive and radioresistant cells, and investigated the underlying mechanisms. We used an adenovirus expressing the hepatocyte growth factor antagonist, NK4 (Ad-NK4), as a representative gene therapy. We established two radioresistant human pancreatic cancer cell lines using fractionated irradiation. Radiosensitive and radioresistant pancreatic cancer cells were infected with Ad-NK4, and NK4 levels in the cells were measured. In order to investigate the mechanisms responsible for the differences in the transduction efficiency between these cells, we measured expression of the genes mediating adenovirus infection and endocytosis. The results revealed that NK4 levels in radioresistant cells were significantly lower (P<0.01) than those in radiosensitive cells, although there were no significant differences in adenovirus uptake between radiosensitive cells and radioresistant cells. Integrin β3 was up-regulated and the Coxsackie virus and adenovirus receptor was down-regulated in radioresistant cells, and inhibition of integrin β3 promoted adenovirus gene transfer. These results suggest that inhibition of integrin β3 in radioresistant pancreatic cancer cells could enhance adenovirus-mediated gene therapy. (author)

  15. Searching for a strategy to gamma-sterilize Portuguese cork stoppers - preliminary studies on bioburden, radioresistance and sterility assurance level

    International Nuclear Information System (INIS)

    Botelho, M.L.; Almeida-Vara, E.; Andrade, M.E.; Tenreiro, R.

    1988-01-01

    A gamma radiation plant will start running next year in Portugal, to sterilize medical devices and wine cork stoppers. As Portugal is the first world producer, manufacturer and exporter of wine cork stoppers, an efficient sterilizing procedure is required to overcome moulding from long term shipping. Preliminary research on cork stoppers bioburden and microflora radioresistance allowed to establish reliable D 10 and Sterility Assurance Level (SAL) values. Studied samples showed an initial average contamination of about 10 4 c.f.u. per cork stopper. The determined D 10 values for fungi were not higher than 2 kGy. In these conditions, a SAL of 10 -4 can be expected when the product is treated at a minimum absorbed dose of 15 kGy. (author)

  16. Suppression of in vitro cell-mediated lympholysis generation by alloactivated lymphocytes. Examination of radioresistant suppressive activity

    International Nuclear Information System (INIS)

    Orosz, C.G.; Ferguson, R.M.

    1986-01-01

    We investigated the radioresistant (1000 rads) suppression of CML generation mediated by alloactivated murine splenocytes. Suppressive cells were generated in MLCs by stimulation of (A X 6R)F1 splenocytes with irradiated C57BL/10 splenocytes. Suppressive cells could lyse targets bearing H-2b alloantigens, but would not lyse parental B10.T(6R) or B10.A targets. Suppressive activity was detected by including the alloactivated (A X 6R)F1 cells in B10.T(6R) anti-B10.A(1R) MLCs. Relative to the suppressive (A X 6R)F1 cells, the B10.A(1R) lymphocytes display both parental and suppressor-inducing alloantigens. In the absence of a suppressive population, B10.A(1R) stimulators cause B10.T(6R) splenocytes to generate cytolytic activity specific for both H-2Db (suppressor-inducing) and H-2Kk (suppressor-borne) target determinants. The irradiated, alloactivated (A X 6R)F1 cells decrease the H-2Db-specific CML generated in this system, thus mediating apparent antigen-specific suppression. However, cytolytic activity concomitantly generated in the same culture against the unrelated H-2Kk target determinants is similarly reduced by the (A X 6R)F1 cells. Thus, radioresistant suppression by alloactivated splenocytes is not necessarily antigen-specific. The irradiated (A X 6R)F1 cells would not suppress the generation of H-2Kk-specific CTL in B10.T(6R) anti-B10.A MLCs. Hence, the irradiated (A X 6R)F1 cells can impede CML generation against third-party alloantigens if, and only if, those alloantigens are coexpressed with suppressor-inducing alloantigens on the stimulator cells in suppressed MLCs. Similar results were also obtained using a different histoincompatible lymphocyte combination

  17. Radioresistance of aboriginal earthworms of Absheron peninsula in radioactive model systems

    International Nuclear Information System (INIS)

    Suleymanova, A.S.; Garibov, A.A.; Abdullayev, A.A.; Naghiyev, J.A.; Farajov, M.F.; Samedov, P.A.

    2011-01-01

    Full tex:Soil animals are the most suitable biological indicators of radioactive pollution because they are parts of nutritional chains and webs, occur in relatively high numbers and can be collected during most parts of the year.The use of earthworms in the soils from Ramana iodine plant area of Absheron peninsula, which is rich with radionuclide and in the soil mixed with RaCl2 and UO2SO4 salt solutions in different concentrations, for resistance to ionizing radiation in soil is reviewed.Effect of radionuclides on vital functions of earthworms and determination of radionuclides (before and after experiments) in contaminated soils by ?-spectrometer were carried out in laboratory condition during a month. Regarding to ?-spectrometric results there were determined that earthworms had absorbed most of radioactive elements and allocated them as coprogenous substances on the upper layer of soil. In Ramana soils mostly the 238U radionuclides were highly accumulated in gut cells of the earthworms. By the influence of radioactive elements it was shown that the earthworms from Ramana iodine plant territory variants had proved particularly sensitive to an increased Ra-radiation background and to iodine factor.It was interestingly established the proportional dependence between rising level of accumulation in earthworms' body and in their coprolites and increasing of radioactive salts containing in the soils treated by UO2SO4 and RaCl2 solutions.Thus there is different level of radioresistance for earthworms and they are among the best bioindicators of polluted soils. There was an obvious perspective of using of earthworms as bioremediators in polluted soil with radionuclides in future as well.

  18. Isolation and identification of radioprotective compound (s) from radioresistant culture of Fusarium Moniliforme

    International Nuclear Information System (INIS)

    Adam, Y.M.; Attaby, H.S.H.

    2001-01-01

    Mat extract and filtrate of the radio-resistant strain Fusarium Moniliforme have been prepared and tested for their radioprotective action on the radiosensitive strain Trichoderma Viride. Both extracts gave T. Viride a protective effect against gamma radiation. Analysis of mat extracts and filtrates of both fungi, the radioresistant F. Moniliforme and the radiosensitive T. Viride revealed a pronounced differences in amino acids quantities in addition to the presence of gibberelic acid (GA 3 ) in the filtrate of F. Moniliforme only. Generally, the radioresistant fungus F. Moniliforme was able to accumulate ten amino acids in large quantity than the radiosensitive one. These amino acids comprised, cystine, glutamic acid, serine, methionine, histidine, proline, arginine, alanine, glycine and therionine. The amino acid pool of both fungi was poor in filtrate than in the mat extract. Analysis of filtration of F. Moniliforme was characterized by high content of gibberellic acid, whereas, only traces were detected in mat extract. No gibberellic acid was detected in both mat extract and filtrate of T. Viride. The results of this investigation, revealed also that both amino acids and gibberellic acid were subjected to pronounced disturbances following irradiation compared with the control. A close correlation between the induced radioresistance of T. Viride and the amounts of amino acids and G A, added to its culture medium was observed, suggesting their participation in radioprotection

  19. Radioresistance related genes screened by protein-protein interaction network analysis in nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Zhu Xiaodong; Guo Ya; Qu Song; Li Ling; Huang Shiting; Li Danrong; Zhang Wei

    2012-01-01

    Objective: To discover radioresistance associated molecular biomarkers and its mechanism in nasopharyngeal carcinoma by protein-protein interaction network analysis. Methods: Whole genome expression microarray was applied to screen out differentially expressed genes in two cell lines CNE-2R and CNE-2 with different radiosensitivity. Four differentially expressed genes were randomly selected for further verification by the semi-quantitative RT-PCR analysis with self-designed primers. The common differentially expressed genes from two experiments were analyzed with the SNOW online database in order to find out the central node related to the biomarkers of nasopharyngeal carcinoma radioresistance. The expression of STAT1 in CNE-2R and CNE-2 cells was measured by Western blot. Results: Compared with CNE-2 cells, 374 genes in CNE-2R cells were differentially expressed while 197 genes showed significant differences. Four randomly selected differentially expressed genes were verified by RT-PCR and had same change trend in consistent with the results of chip assay. Analysis with the SNOW database demonstrated that those 197 genes could form a complicated interaction network where STAT1 and JUN might be two key nodes. Indeed, the STAT1-α expression in CNE-2R was higher than that in CNE-2 (t=4.96, P<0.05). Conclusions: The key nodes of STAT1 and JUN may be the molecular biomarkers leading to radioresistance in nasopharyngeal carcinoma, and STAT1-α might have close relationship with radioresistance. (authors)

  20. DNA repair and cytokines: TGF-beta, IL-6, and thrombopoietin as different biomarkers of radioresistance

    Directory of Open Access Journals (Sweden)

    Francesca Bianca Aiello

    2016-07-01

    Full Text Available Double strand breaks (DSBs induced by radiotherapy are highly cytotoxic lesions, leading to chromosomal aberrations and cell death. ATM-dependent DNA-damage response, non-homologous end joining, and homologous recombination pathways coordinately contribute to repairing DSBs in higher eukaryotes. It is known that the expression of DSB repair genes is increased in tumors which is one of the main reasons for radioresistance. The inhibition of DSB repair pathways may be useful to increase tumor cell radiosensitivity and may target stem cell-like cancer cells, known to be the most radioresistant tumor components. Commonly overexpressed in neoplastic cells, cytokines confer radioresistance by promoting proliferation, survival, invasion, and angiogenesis. Unfortunately, tumor irradiation increases the expression of various cytokines displaying these effects, including transforming growth factor-beta and interlukin-6. Recently the capabilities of these cytokines to support DNA repair pathways and the ATM-dependent DNA response have been demonstrated. Thrombopoietin, essential for megakaryopoiesis and very important for hematopoietic stem cell homeostasis, has also been found to promote DNA repair in a highly selective manner. These findings reveal a novel mechanism underlying cytokine-related radioresistance, which may be clinically relevant. Therapies targeting specific cytokines may be used to improve radiosensitivity. Specific inhibitors may be chosen in consideration of different tumor microenvironments. Thrombopoietin may be useful in fending off irradiation-induced loss of hematopoietic stem cells.

  1. HIF-1 and NDRG2 contribute to hypoxia-induced radioresistance of cervical cancer Hela cells

    International Nuclear Information System (INIS)

    Liu, Junye; Zhang, Jing; Wang, Xiaowu; Li, Yan; Chen, Yongbin; Li, Kangchu; Zhang, Jian; Yao, Libo; Guo, Guozhen

    2010-01-01

    Hypoxia inducible factor 1 (HIF-1), the key mediator of hypoxia signaling pathways, has been shown involved in hypoxia-induced radioresistance. However, the underlying mechanisms are unclear. The present study demonstrated that both hypoxia and hypoxia mimetic cobalt chloride could increase the radioresistance of human cervical cancer Hela cells. Meanwhile, ectopic expression of HIF-1 could enhance the resistance of Hela cells to radiation, whereas knocking-down of HIF-1 could increase the sensitivity of Hela cells to radiation in the presence of hypoxia. N-Myc downstream-regulated gene 2 (NDRG2), a new HIF-1 target gene identified in our lab, was found to be upregulated by hypoxia and radiation in a HIF-1-dependent manner. Overexpression of NDRG2 resulted in decreased sensitivity of Hela cells to radiation while silencing NDRG2 led to radiosensitization. Moreover, NDRG2 was proved to protect Hela cells from radiation-induced apoptosis and abolish radiation-induced upregulation of Bax. Taken together, these data suggest that both HIF-1 and NDRG2 contribute to hypoxia-induced tumor radioresistance and that NDRG2 acts downstream of HIF-1 to promote radioresistance through suppressing radiation-induced Bax expression. It would be meaningful to further explore the clinical application potential of HIF-1 and NDRG2 blockade as radiosensitizer for tumor therapy.

  2. GPR56/ADGRG1 Inhibits Mesenchymal Differentiation and Radioresistance in Glioblastoma

    NARCIS (Netherlands)

    Moreno, Marta; Pedrosa, Leire; Pare, Laia; Pineda, Estela; Bejarano, Leire; Martinez, Josefina; Balasubramaniyan, Veerakumar; Ezhilarasan, Ravesanker; Kallarackal, Naveen; Kim, Sung-Hak; Wang, Jia; Audia, Alessandra; Conroy, Siobhan; Marin, Mercedes; Ribalta, Teresa; Pujol, Teresa; Herreros, Antoni; Tortosa, Avelina; Mira, Helena; Alonso, Marta M.; Gomez-Manzano, Candelaria; Graus, Francesc; Sulman, Erik P.; Piao, Xianhua; Nakano, Ichiro; Prat, Aleix; Bhat, Krishna P.; de la Iglesia, Nuria

    2017-01-01

    A mesenchymal transition occurs both during the natural evolution of glioblastoma (GBM) and in response to therapy. Here, we report that the adhesion G-protein-coupled receptor, GPR56/ADGRG1, inhibits GBM mesenchymal differentiation and radioresistance. GPR56 is enriched in proneural and

  3. Beclin1-induced autophagy abrogates radioresistance of lung cancer cells by suppressing osteopontin

    International Nuclear Information System (INIS)

    Chang, Seung-Hee; Minai-Tehrani, Arash; Shin, Ji-Young

    2012-01-01

    Osteopontin (OPN) serves as an indicator of resistance to radiotherapy. However, the role of OPN in the development of acquired radioresistance in human lung cancer cells has not yet been fully elucidated. Therefore, the potential importance of OPN as a marker of lung cancer with a potential significant role in the development of radioresistance against repeated radiotherapy has prompted us to define the pathways by which OPN regulates lung cancer cell growth. In addition, autophagy has been reported to play a key role in the radiosensitization of cancer cells. Here, we report that increased OPN expression through induction of nuclear p53 following irradiation was inhibited by exogenous beclin-1 (BECN1). Our results clearly show that BECN1 gene expression led to induction of autophagy and inhibition of cancer cell growth and angiogenesis. Our results suggest that the induction of autophagy abrogated the radioresistance of the cancer cells. Interestingly, we showed that knockdown of OPN by lentivirus-mediated shRNA induced the autophagy of human lung cancer cell. Taken together, these results suggest that OPN and BECN1 can be molecular targets for overcoming radioresistance by controlling autophagy. (author)

  4. CD133-expressing thyroid cancer cells are undifferentiated, radioresistant and survive radioiodide therapy

    International Nuclear Information System (INIS)

    Ke, Chien-Chih; Liu, Ren-Shyan; Yang, An-Hang; Liu, Ching-Sheng; Chi, Chin-Wen; Tseng, Ling-Ming; Tsai, Yi-Fan; Ho, Jennifer H.; Lee, Chen-Hsen; Lee, Oscar K.

    2013-01-01

    131 I therapy is regularly used following surgery as a part of thyroid cancer management. Despite an overall relatively good prognosis, recurrent or metastatic thyroid cancer is not rare. CD133-expressing cells have been shown to mark thyroid cancer stem cells that possess the characteristics of stem cells and have the ability to initiate tumours. However, no studies have addressed the influence of CD133-expressing cells on radioiodide therapy of the thyroid cancer. The aim of this study was to investigate whether CD133 + cells contribute to the radioresistance of thyroid cancer and thus potentiate future recurrence and metastasis. Thyroid cancer cell lines were analysed for CD133 expression, radiosensitivity and gene expression. The anaplastic thyroid cancer cell line ARO showed a higher percentage of CD133 + cells and higher radioresistance. After γ-irradiation of the cells, the CD133 + population was enriched due to the higher apoptotic rate of CD133 - cells. In vivo 131 I treatment of ARO tumour resulted in an elevated expression of CD133, Oct4, Nanog, Lin28 and Glut1 genes. After isolation, CD133 + cells exhibited higher radioresistance and higher expression of Oct4, Nanog, Sox2, Lin28 and Glut1 in the cell line or primarily cultured papillary thyroid cancer cells, and lower expression of various thyroid-specific genes, namely NIS, Tg, TPO, TSHR, TTF1 and Pax8. This study demonstrates the existence of CD133-expressing thyroid cancer cells which show a higher radioresistance and are in an undifferentiated status. These cells possess a greater potential to survive radiotherapy and may contribute to the recurrence of thyroid cancer. A future therapeutic approach for radioresistant thyroid cancer may focus on the selective eradication of CD133 + cells. (orig.)

  5. 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

  6. Bcl-2 inhibitors potentiate the cytotoxic effects of radiation in Bcl-2 overexpressing radioresistant tumor cells

    International Nuclear Information System (INIS)

    Hara, Takamitsu; Omura-Minamisawa, Motoko; Chao Cheng; Nakagami, Yoshihiro; Ito, Megumi; Inoue, Tomio

    2005-01-01

    Purpose: Bcl-2, an inhibitor of apoptosis frequently shows elevated expression in human tumors, thus resulting in resistance to radiation therapy. Therefore, inhibiting Bcl-2 function may enhance the radiosensitivity of tumor cells. Tetrocarcin A (TC-A) and bcl-2 antisense oligonucleotides exhibit antitumor activity by inhibiting Bcl-2 function and transcription, respectively. We investigated whether these antitumor agents would enhance the cytotoxic effects of radiation in tumor cells overexpressing Bcl-2. Methods and materials: We used HeLa/bcl-2 cells, a stable Bcl-2-expressing cell line derived from wild-type HeLa (HeLa/wt) cells. Cells were incubated with TC-A and bcl-2 antisense oligonucleotides for 24 h after irradiation, and cell viability was then determined. Apoptotic cells were quantified by flow cytometric assay. Results: The HeLa/bcl-2 cells were more resistant to radiation than HeLa/wt cells. At concentrations that are not inherently cytotoxic, both TC-A and bcl-2 antisense oligonucleotides increased the cytotoxic effects of radiation in HeLa/bcl-2 cells, but not in HeLa/wt cells. However, in HeLa/bcl-2 cells, additional treatment with TC-A in combination with radiation did not significantly increase apoptosis. Conclusions: The present results suggest that TC-A and bcl-2 antisense oligonucleotides reduce radioresistance of tumor cells overexpressing Bcl-2. Therefore, a combination of radiotherapy and Bcl-2 inhibitors may prove to be a useful therapeutic approach for treating tumors that overexpress Bcl-2

  7. Reciprocal Regulation of Hypoxia-Inducible Factor 2α and GLI1 Expression Associated With the Radioresistance of Renal Cell Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Jiancheng [Department of Urology, First Affiliated Hospital of Medical School, Xi' an Jiaotong University, Xi' an (China); Department of Urology, Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Wu, Kaijie [Department of Urology, First Affiliated Hospital of Medical School, Xi' an Jiaotong University, Xi' an (China); Gao, Dexuan [Department of Urology, Shandong Provincial Hospital affiliated with Shandong University, Ji' nan (China); Zhu, Guodong; Wu, Dapeng; Wang, Xinyang; Chen, Yule; Du, Yuefeng; Song, Wenbin; Ma, Zhenkun [Department of Urology, First Affiliated Hospital of Medical School, Xi' an Jiaotong University, Xi' an (China); Authement, Craig; Saha, Debabrata [Department of Urology, Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Hsieh, Jer-Tsong, E-mail: jt.hsieh@utsouthwestern.edu [Department of Urology, Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); He, Dalin, E-mail: dalinhe@yahoo.com [Department of Urology, First Affiliated Hospital of Medical School, Xi' an Jiaotong University, Xi' an (China)

    2014-11-15

    Purpose: Renal cell carcinoma (RCC) is often considered a radioresistant tumor, but the molecular mechanism underlying its radioresistance is poorly understood. This study explored the roles of hypoxia-inducible factor 2α (HIF2α) and sonic hedgehog (SHH)-GLI1 signaling in mediating the radioresistance of RCC cells and to unveil the interaction between these 2 signaling pathways. Methods and Materials: The activities of SHH-GLI1 signaling pathway under normoxia and hypoxia in RCC cells were examined by real-time polymerase chain reaction, Western blot, and luciferase reporter assay. The expression of HIF2α and GLI1 in RCC patients was examined by immunohistochemistry, and their correlation was analyzed. Furthermore, RCC cells were treated with HIF2α-specific shRNA (sh-HIF2α), GLI1 inhibitor GANT61, or a combination to determine the effect of ionizing radiation (IR) on RCC cells based on clonogenic assay and double-strand break repair assay. Results: RCC cells exhibited elevated SHH-GLI1 activities under hypoxia, which was mediated by HIF2α. Hypoxia induced GLI1 activation through SMO-independent pathways that could be ablated by PI3K inhibitor or MEK inhibitor. Remarkably, the SHH-GLI1 pathway also upregulated HIF2α expression in normoxia. Apparently, there was a positive correlation between HIF2α and GLI1 expression in RCC patients. The combination of sh-HIF2α and GLI1 inhibitor significantly sensitized RCC cells to IR. Conclusions: Cross-talk between the HIF2α and SHH-GLI1 pathways was demonstrated in RCC. Cotargeting these 2 pathways, significantly sensitizing RCC cells to IR, provides a novel strategy for RCC treatment.

  8. Prognostic factors for outcomes after whole-brain irradiation of brain metastases from relatively radioresistant tumors: a retrospective analysis

    NARCIS (Netherlands)

    Meyners, T.; Heisterkamp, C.; Kueter, J.D.; Veninga, T.; Stalpers, L.J.A.; Schild, S.E.; Rades, D.

    2010-01-01

    Background: This study investigated potential prognostic factors in patients treated with whole-brain irradiation (WBI) alone for brain metastases from relatively radioresistant tumors such as malignant melanoma, renal cell carcinoma, and colorectal cancer. Additionally, a potential benefit from

  9. Prognostic factors for outcomes after whole-brain irradiation of brain metastases from relatively radioresistant tumors: a retrospective analysis

    NARCIS (Netherlands)

    Meyners, Thekla; Heisterkamp, Christine; Kueter, Jan-Dirk; Veninga, Theo; Stalpers, Lukas J. A.; Schild, Steven E.; Rades, Dirk

    2010-01-01

    This study investigated potential prognostic factors in patients treated with whole-brain irradiation (WBI) alone for brain metastases from relatively radioresistant tumors such as malignant melanoma, renal cell carcinoma, and colorectal cancer. Additionally, a potential benefit from escalating the

  10. Transmission of in-vitro radioresistance in a cancer-prone family

    International Nuclear Information System (INIS)

    Bech-Hansen, N.T.; Blattner, W.A.; Sell, B.M.; McKeen, E.A.; Lampkin, B.C.; Fraumeni, J.F. Jr.; Paterson, M.C.

    1981-01-01

    Neoplasms of possible radiogenic origin developed in two members of a family prone to a diversity of cancers. Gamma-irradiation survival studies in these two patients and three other relatives, but not their spouses, over three generations demonstrated resistance to cell killing. The D 10 value (radiation dose required to reduce survival to 10%) was significantly higher for the five radioresistant strains (491 +- 30 rad) than for control cultures (405 +- 18 rad). There was a significant correlation between individual D 10 values and D 0 survival-curve parameters, indicating that changes in the exponential slope of the survival curves accounted for much of the increase in D 10 values. This novel radiation phenotype could be a manifestation of a basic cellular defect, predisposing to a variety of tumours in family members. Thus in-vitro radioresistance, like radiosensitivity, may be a phenotype of a mechanism that increases cancer risk in man. (author)

  11. Highly radioresistant aramid fiber as a concrete-reinforcing material. Development of reinforced compound materials

    International Nuclear Information System (INIS)

    Udagawa, Akira; Moriya, Toshio.

    1997-01-01

    Nuclear installations, such as nuclear fusion reactor always receive strong influence from magnetic field. There, stray current is induced by the changes in magnetic fields among iron rods of the construction, resulting that the plasma control magnetic field might be disturbed. As the countermeasures for these troubles, iron rods mixed with non-magnetic Mn-steel have been used in JAERI, but it is insufficient to completely prevent such electromagnetic damages. Thus, aramid fiber reinforced plastics (ArFRP) was paid an attention as a concrete-reinforcing material. JAERI has been attempting to develop a radioresistant ArFRP jointly with Mitsui Construction Co., Ltd. and a highly efficient producing process of ArFRP was developed. The product had superior properties in respects of radioresistancy, heat-resistancy and durability. The properties of newly developed ArFRP rods were compared with those of the conventional ArFRP and iron rods. (M.N.)

  12. Clinically relevant radioresistant cells efficiently repair DNA double-strand breaks induced by X-rays

    International Nuclear Information System (INIS)

    Kuwahara, Yoshikazu; Baba, Taisuke; Nakagawa, Hironobu; Shimura, Tsutomu; Yamamoto, Yoichiro; Fukumoto, Manabu; Li Li; Ohkubo, Yasuhito

    2009-01-01

    Radiotherapy is one of the major therapeutic modalities for eradicating malignant tumors. However, the existence of radioresistant cells remains one of the most critical obstacles in radiotherapy and radiochemotherapy. Standard radiotherapy for tumor treatment consists of approximately 2 Gy once a day, 5 days a week, over a period of 5-8 weeks. To understand the characteristics of radioresistant cells and to develop more effective radiotherapy, we established a novel radioresistant cell line, HepG2-8960-R with clinical relevance from parental HepG2 cells by long-term fractionated exposure to 2 Gy of X-rays. HepG2-8960-R cells continued to proliferate with daily exposure to 2 Gy X-rays for more than 30 days, while all parental HepG2 cells ceased. After exposure to fractionated 2 Gy X-rays, induction frequencies of micronuclei and remaining foci of γ-H2AX in HepG2-8960-R were less than those in HepG2. Flow cytometric analysis revealed that the proportion of cells in S- and G2/M-phase of the cell cycle was higher in HepG2-8960-R than in HepG2. These suggest that the response of clinically relevant radioresistant (CRR) cells to fractionated radiation is not merely an accumulated response to each fractionated radiation. This is the first report on the establishment of a CRR cell line from an isogenic parental cell line. (author)

  13. Alterations in gene expression profiles between radioresistant and radiosensitive cell lines

    International Nuclear Information System (INIS)

    Zhou Fuxiang; Zhou Yunfeng; Xie Conghua; Dai Jing; Cao Zhen; Yu Haijun; Liao Zhengkai; Luo Zhiguo

    2007-01-01

    Objective: To study the-difference of gene expressions by the contrastive model including the cells with same pathological origin and genetic background, but definitely different radioresponse, and to find the main molecular targets related to radiosensitivity. Methods: Human larynx squamous carcinoma cell, Hep -2 was irradiated with dose of 637 cGy repeatedly to establish a radioresistant daughter cell line. The radiobiology characteristics were obtained using clone forming assay. The difference of gene expression between parent and daughter cells was detected by cDNA microarray using two different arrays including 14000 genes respectively. Results: A radioresistant cell strain Hep-2R was isolated from its parental strain Hep-2 cell. The SF 2 , D 0 , α, β for Hep-2R cell line were 0.6798, 3.24, 0.2951 and 0.0363, respectively, while 0.4148, 2.06, 0.1074 and 0.0405 for Hep-2, respectively (for SF 2 , χ 2 =63.957, P<0.001). Compared with Hep-2 cells, the expressions of 41 genes were significantly altered in the radioresistant Hep-2R cells, including 22 genes up-regulated and 19 genes down-regulated, which were involved in DNA repair, regulation of the cell cycle, cell proliferation, cytoskeleton, protein synthesis, cellular metabolism and especially apoptosis which is responsible for the different radiosensitivity between these two larynx cancer cells. The telomere protection protein gene, POT1, was the mostly up-regulated by 3.348 times. Conclusions: There is difference of gene expression between the radioresistant contrastive models. POT1 gene may be the target of radiosensitization. (authors)

  14. Factors implicated to radioresistance of breast cancer and their possible roles

    International Nuclear Information System (INIS)

    Yan Weili; Huang Gang

    2006-01-01

    Radiotherapy plays an important role in the management of breast cancer. The recurrence of breast cancer after radiotherapy is considered to be related with radioresistance in breast cancer cells. Various factors, extranuclear and intranuclear, such as insulin-like growth factor-1 receptor, phosphatidylinositol 3-kinase pathway, epidermal growth factor, human epidermal growth factor receptors, p53, c-erb B2, Bcl-2, BRCA1, BRCA2, telomeres and gene expression signature, that have been implicated to influence the radiation response. (authors)

  15. Bmi-1 confers adaptive radioresistance to KYSE-150R esophageal carcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Guanyu [Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou (China); Liu, Luying [Department of Radiotherapy, Zhejiang Cancer Hospital, Hangzhou (China); Sharma, Sherven [David Geffen School of Medicine at UCLA, and the Department of Veterans Affairs, Los Angeles, CA (United States); Liu, Hai; Yang, Weifang; Sun, Xiaonan [Department of Radiotherapy, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou (China); Dong, Qinghua, E-mail: dongqinghua@zju.edu.cn [Biomedical Research Center, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou (China)

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer Adaptive radioresistant KYSE-150R cells expressed high level of Bmi-1. Black-Right-Pointing-Pointer Bmi-1 depletion sensitized KYSE-150R cells to RT. Black-Right-Pointing-Pointer Bmi-1 depletion increased the generation of ROS in KYSE-150R cells exposed to radiation. Black-Right-Pointing-Pointer Bmi-1 depletion impaired DNA repair capacities in KYSE-150R cells exposed to radiation. -- Abstract: Radiotherapy (RT) is a major modality of cancer treatment. However, tumors often acquire radioresistance, which causes RT to fail. The exact mechanisms by which tumor cells subjected to fractionated irradiation (FIR) develop an adaptive radioresistance are largely unknown. Using the radioresistant KYSE-150R esophageal squamous cell carcinoma (ESCC) model, which was derived from KYSE-150 parental cells using FIR, the role of Bmi-1 in mediating the radioadaptive response of ESCC cells to RT was investigated. The results showed that the level of Bmi-1 expression was significantly higher in KYSE-150R cells than in the KYSE-150 parental cells. Bmi-1 depletion sensitized the KYSE-150R cells to RT mainly through the induction of apoptosis, partly through the induction of senescence. A clonogenic cell survival assay showed that Bmi-1 depletion significantly decreased the radiation survival fraction in KYSE-150R cells. Furthermore, Bmi-1 depletion increased the generation of reactive oxygen species (ROS) and the expression of oxidase genes (Lpo, Noxo1 and Alox15) in KYSE-150R cells exposed to irradiation. DNA repair capacities assessed by {gamma}-H2AX foci formation were also impaired in the Bmi-1 down-regulated KYSE-150R cells. These results suggest that Bmi-1 plays an important role in tumor radioadaptive resistance under FIR and may be a potent molecular target for enhancing the efficacy of fractionated RT.

  16. Recovery and radio-resistance in mice after external irradiation; Restauration et radio-resistance chez la souris apres irradiation externe

    Energy Technology Data Exchange (ETDEWEB)

    Le Guillou, S [Commissariat a l' Energie Atomique, Fontenay-aux-Roses (France). Centre d' Etudes Nucleaires

    1965-07-01

    The author presents a literature study concerning recovery from external irradiation and an analysis of experimental data (which appear to suggest the idea of a radio-resistance in animals), as well as the hypotheses put forward for explaining this phenomenon. The author then describes an experiment carried out on mice whose LD 50/30 days increased from 1005 to 1380 rads and for which it was shown that an increase occurs in the number of certain anti-bodies circulating after a low dose of {gamma} irradiation. (author) [French] L'auteur presente une etude bibliographique de la restauration apres irradiation externe et une analyse des donnees experimentales qui paraissent suggerer la notion de radioresistance chez les animaux ainsi que les hypotheses cherchant a expliquer ce phenomene. Il relate ensuite une experience realisee sur des souris dont la DL 50/30 jours est passee de 1005 a 1380 rads et dans laquelle est montree l'augmentation de certains anticorps circulant apres une faible dose d'irradiation gamma. (auteur)

  17. Recovery and radio-resistance in mice after external irradiation; Restauration et radio-resistance chez la souris apres irradiation externe

    Energy Technology Data Exchange (ETDEWEB)

    Le Guillou, S. [Commissariat a l' Energie Atomique, Fontenay-aux-Roses (France). Centre d' Etudes Nucleaires

    1965-07-01

    The author presents a literature study concerning recovery from external irradiation and an analysis of experimental data (which appear to suggest the idea of a radio-resistance in animals), as well as the hypotheses put forward for explaining this phenomenon. The author then describes an experiment carried out on mice whose LD 50/30 days increased from 1005 to 1380 rads and for which it was shown that an increase occurs in the number of certain anti-bodies circulating after a low dose of {gamma} irradiation. (author) [French] L'auteur presente une etude bibliographique de la restauration apres irradiation externe et une analyse des donnees experimentales qui paraissent suggerer la notion de radioresistance chez les animaux ainsi que les hypotheses cherchant a expliquer ce phenomene. Il relate ensuite une experience realisee sur des souris dont la DL 50/30 jours est passee de 1005 a 1380 rads et dans laquelle est montree l'augmentation de certains anticorps circulant apres une faible dose d'irradiation gamma. (auteur)

  18. E-Cadherin loss associated with EMT promotes radioresistance in human tumor cells

    International Nuclear Information System (INIS)

    Theys, Jan; Jutten, Barry; Habets, Roger; Paesmans, Kim; Groot, Arjan J.; Lambin, Philippe; Wouters, Brad G.; Lammering, Guido; Vooijs, Marc

    2011-01-01

    Background and purpose: Hypoxia is a hallmark of solid cancers and associated with metastases and treatment failure. During tumor progression epithelial cells often acquire mesenchymal features, a phenomenon known as epithelial-to-mesenchymal transition (EMT). Intratumoral hypoxia has been linked to EMT induction. We hypothesized that signals from the tumor microenvironment such as growth factors and tumor oxygenation collaborate to promote EMT and thereby contribute to radioresistance. Materials and methods: Gene expression changes under hypoxia were analyzed using microarray and validated by qRT-PCR. Conversion of epithelial phenotype upon hypoxic exposure, TGFβ addition or oncogene activation was investigated by Western blot and immunofluorescence. Cell survival following ionizing radiation was assayed using clonogenic survival. Results: Upon hypoxia, TGFβ addition or EGFRvIII expression, MCF7, A549 and NMuMG epithelial cells acquired a spindle shape and lost cell-cell contacts. Expression of epithelial markers such as E-cadherin decreased, whereas mesenchymal markers such as vimentin and N-cadherin increased. Combining hypoxia with TGFβ or EGFRvIII expression, lead to more rapid and pronounced EMT-like phenotype. Interestingly, E-cadherin expression and the mesenchymal appearance were reversible upon reoxygenation. Mesenchymal conversion and E-cadherin loss were associated with radioresistance. Conclusions: Our findings describe a mechanism by which the tumor microenvironment may contribute to tumor radioresistance via E-cadherin loss and EMT.

  19. Energetic heavy ions overcome tumor radioresistance caused by overexpression of Bcl-2

    International Nuclear Information System (INIS)

    Hamada, Nobuyuki; Hara, Takamitsu; Omura-Minamisawa, Motoko; Funayama, Tomoo; Sakashita, Tetsuya; Sora, Sakura; Yokota, Yuichiro; Nakano, Takashi

    2008-01-01

    Background and purpose: Overexpression of Bcl-2 is frequent in human cancers and has been associated with radioresistance. Here we investigated the potential impact of heavy ions on Bcl-2 overexpressing tumors. Materials and methods: Bcl-2 cells (Bcl-2 overexpressing HeLa cells) and Neo cells (neomycin resistant gene-expressing HeLa cells) exposed to γ-rays or heavy ions were assessed for the clonogenic survival, apoptosis and cell cycle distribution. Results: Whereas Bcl-2 cells were more resistant to γ-rays (0.2 keV/μm) and helium ions (16.2 keV/μm) than Neo cells, heavy ions (76.3-1610 keV/μm) yielded similar survival regardless of Bcl-2 overexpression. Carbon ions (108 keV/μm) decreased the difference in the apoptotic incidence between Bcl-2 and Neo cells, and prolonged G 2 /M arrest that occurred more extensively in Bcl-2 cells than in Neo cells. Conclusions: High-LET heavy ions overcome tumor radioresistance caused by Bcl-2 overexpression, which may be explained at least in part by the enhanced apoptotic response and prolonged G 2 /M arrest. Thus, heavy-ion therapy may be a promising modality for Bcl-2 overexpressing radioresistant tumors

  20. Dexamethasone-induced radioresistance occurring independent of human papilloma virus gene expression in cervical carcinoma cells

    International Nuclear Information System (INIS)

    Rutz, H.P.; Mariotta, M.; Mirimanoff, R.O.; Knebel Doeberitz, M. von

    1998-01-01

    The aim of this study was to investigate the role of HPV 18 E6 and E7 gene products with respect to radiosensitivity of two cervical carcinoma cell lines. The two cervical carcinoma lines C4-1 and SW 756 were used in which treatment with dexamethasone allows to modulate expression levels of HPV 18 E6 and E7 genes: Upregulation in C4-1, down-regulation in SW 756. Effects of treatment with dexamethasone on plating efficiency and radiosensitivity were assessed using a clonogenic assay. Treatment with dexamethasone increased plating efficiency of the C4-1 cells, but did not affect plating efficiency of SW 756 cells. Treatment with dexamethasone induced enhanced radioresistance in both cell lines. Thus, in C4-1 cells the observed changes in radioresistance correlate to the enhancement in expression of HPV 18 genes E6/E7, whereas in SW 756, a reduced expression correlates negatively with the enhanced radioresistance. (orig./MG) [de

  1. Hypoxia-inducible factor 1–mediated characteristic features of cancer cells for tumor radioresistance

    International Nuclear Information System (INIS)

    Harada, Hiroshi

    2016-01-01

    Tumor hypoxia has been attracting increasing attention in the fields of radiation biology and oncology since Thomlinson and Gray detected hypoxic cells in malignant solid tumors and showed that they exert a negative impact on the outcome of radiation therapy. This unfavorable influence has, at least partly, been attributed to cancer cells acquiring a radioresistant phenotype through the activation of the transcription factor, hypoxia-inducible factor 1 (HIF-1). On the other hand, accumulating evidence has recently revealed that, even though HIF-1 is recognized as an important regulator of cellular adaptive responses to hypoxia, it may not become active and induce tumor radioresistance under hypoxic conditions only. The mechanisms by which HIF-1 is activated in cancer cells not only under hypoxic conditions, but also under normoxic conditions, through cancer-specific genetic alterations and the resultant imbalance in intermediate metabolites have been summarized herein. The relevance of the HIF-1–mediated characteristic features of cancer cells, such as the production of antioxidants through reprogramming of the glucose metabolic pathway and cell cycle regulation, for tumor radioresistance has also been reviewed

  2. Sensitization of Radioresistant Prostate Cancer Cells by Resveratrol Isolated from Arachis hypogaea Stems.

    Science.gov (United States)

    Chen, Yu-An; Lien, Hsiu-Man; Kao, Min-Chuan; Lo, U-Ging; Lin, Li-Chiung; Lin, Chun-Jung; Chang, Sheau-Jiun; Chen, Chia-Chang; Hsieh, Jer-Tsong; Lin, Ho; Tang, Chih-Hsin; Lai, Chih-Ho

    2017-01-01

    Resveratrol (RV, 3,4',5-trihydroxystilbene) is naturally produced by a wide variety of plants including grapes and peanuts (Arachis hypogaea). However, the yield of RV from peanut stem and its potential radiosensitizing effects in prostate cancer (PCa) have not been well investigated. In this study, we characterized RV in peanut stem extract (PSE) for the first time and showed that both RV and PSE dose-dependently induced cell death in DOC-2/DAB2 interactive protein (DAB2IP)-deficient PCa cells with the radioresistant phenotype. Furthermore, the combination of radiation with either RV or PSE induced the death of radioresistant PCa cells through delayed repair of radiation-induced DNA double-strand break (DSB) and prolonged G2/M arrest, which induced apoptosis. The administration of RV and PSE effectively enhanced radiation therapy in the shDAB2IP PCa xenograft mouse model. These results demonstrate the promising synergistic effect of RV and PSE combined with radiation in the treatment of radioresistant PCa.

  3. GPR56/ADGRG1 Inhibits Mesenchymal Differentiation and Radioresistance in Glioblastoma

    Directory of Open Access Journals (Sweden)

    Marta Moreno

    2017-11-01

    Full Text Available A mesenchymal transition occurs both during the natural evolution of glioblastoma (GBM and in response to therapy. Here, we report that the adhesion G-protein-coupled receptor, GPR56/ADGRG1, inhibits GBM mesenchymal differentiation and radioresistance. GPR56 is enriched in proneural and classical GBMs and is lost during their transition toward a mesenchymal subtype. GPR56 loss of function promotes mesenchymal differentiation and radioresistance of glioma initiating cells both in vitro and in vivo. Accordingly, a low GPR56-associated signature is prognostic of a poor outcome in GBM patients even within non-G-CIMP GBMs. Mechanistically, we reveal GPR56 as an inhibitor of the nuclear factor kappa B (NF-κB signaling pathway, thereby providing the rationale by which this receptor prevents mesenchymal differentiation and radioresistance. A pan-cancer analysis suggests that GPR56 might be an inhibitor of the mesenchymal transition across multiple tumor types beyond GBM.

  4. Transition in Survival From Low-Dose Hyper-Radiosensitivity to Increased Radioresistance Is Independent of Activation of ATM SER1981 Activity

    International Nuclear Information System (INIS)

    Krueger, Sarah A.; Collis, Spencer J.; Joiner, Michael C.; Wilson, George D.; Marples, Brian

    2007-01-01

    Purpose: The molecular basis of low-dose hyper-radiosensitivity (HRS) is only partially understood. The aim of this study was to define the roles of ataxia telangiectasia mutated (ATM) activity and the downstream ATM-dependent G 2 -phase cell cycle checkpoint in overcoming HRS and triggering radiation resistance. Methods and Materials: Survival was measured using a high-resolution clonogenic assay. ATM Ser1981 activation was measured by Western blotting. The role of ATM was determined in survival experiments after molecular (siRNA) and chemical (0.4 mM caffeine) inhibition and chemical (20 μg/mL chloroquine, 15 μM genistein) activation 4-6 h before irradiation. Checkpoint responsiveness was assessed in eight cell lines of differing HRS status using flow cytometry to quantify the progression of irradiated (0-2 Gy) G 2 -phase cells entering mitosis, using histone H3 phosphorylation analysis. Results: The dose-response pattern of ATM activation was concordant with the transition from HRS to radioresistance. However, ATM activation did not play a primary role in initiating increased radioresistance. Rather, a relationship was discovered between the function of the downstream ATM-dependent early G 2 -phase checkpoint and the prevalence and overcoming of HRS. Four cell lines that exhibited HRS failed to show low-dose ( 2 -phase checkpoint. These data suggest that clinical exploitation of HRS could be achieved by combining radiotherapy with chemotherapeutic agents that modulate this cell cycle checkpoint

  5. Acquired radioresistance of cancer and the AKT/GSK3β/cyclin D1 overexpression cycle

    International Nuclear Information System (INIS)

    Shimura, Tsutomu

    2011-01-01

    Fractionated radiotherapy (RT) is widely used in cancer therapy for its advantages in the preservation of normal tissues. However, repopulation of surviving tumor cells during fractionated RT limits the efficacy of RT. In fact, repopulating tumors often acquire radioresistance and this is the major cause of failure of RT. We have recently demonstrated that human tumor cells acquire radioresistance when exposed to fractionated radiation (FR) of X-rays every 12 hours for 1 month. The acquired radioresistance was associated with overexpression of cyclin D1, a result of a series of molecular changes; constitutive activation of DNA-PK and AKT with concomitant down-regulation of glycogen synthase kinase-3β (GSK3β) which results in suppression of cyclin D1 proteolysis. Aberrant cyclin D1 overexpression in S-phase induced DNA double strand breaks which activated DNA-PK and established the vicious cycle of cycling D1 overexpression. This overexpression of cyclin D1 is responsible for the radioresistance phenotype of long-term FR cells, since this phenotype was completely abrogated by treatment of FR cells by the AKT/PKB signaling inhibitor (API-2), an AKT inhibitor or by a Cdk4 inhibitor. Thus, targeting the AKT/GSK3β/cyclin D1/Cdk4 pathway can be an efficient modality to suppress acquired radioresistance of tumor cells. In this article, I overview the newly discovered molecular mechanisms underlying acquired radioresistance of tumor cells induced by FR, and propose a strategy for eradication of tumors using fractionated RT by overcoming tumor radioresistance. (author)

  6. Transient elevation of glycolysis confers radio-resistance by facilitating DNA repair in cells

    International Nuclear Information System (INIS)

    Bhatt, Anant Narayan; Chauhan, Ankit; Khanna, Suchit; Rai, Yogesh; Singh, Saurabh; Soni, Ravi; Kalra, Namita; Dwarakanath, Bilikere S

    2015-01-01

    Cancer cells exhibit increased glycolysis for ATP production (the Warburg effect) and macromolecular biosynthesis; it is also linked with therapeutic resistance that is generally associated with compromised respiratory metabolism. Molecular mechanisms underlying radio-resistance linked to elevated glycolysis remain incompletely understood. We stimulated glycolysis using mitochondrial respiratory modifiers (MRMs viz. di-nitro phenol, DNP; Photosan-3, PS3; Methylene blue, MB) in established human cell lines (HEK293, BMG-1 and OCT-1). Glucose utilization and lactate production, levels of glucose transporters and glycolytic enzymes were investigated as indices of glycolysis. Clonogenic survival, DNA repair and cytogenetic damage were studied as parameters of radiation response. MRMs induced the glycolysis by enhancing the levels of two important regulators of glucose metabolism GLUT-1 and HK-II and resulted in 2 fold increase in glucose consumption and lactate production. This increase in glycolysis resulted in resistance against radiation-induced cell death (clonogenic survival) in different cell lines at an absorbed dose of 5 Gy. Inhibition of glucose uptake and glycolysis (using fasentin, 2-deoxy-D-glucose and 3-bromopyruvate) in DNP treated cells failed to increase the clonogenic survival of irradiated cells, suggesting that radio-resistance linked to inhibition of mitochondrial respiration is glycolysis dependent. Elevated glycolysis also facilitated rejoining of radiation-induced DNA strand breaks by activating both non-homologous end joining (NHEJ) and homologous recombination (HR) pathways of DNA double strand break repair leading to a reduction in radiation-induced cytogenetic damage (micronuclei formation) in these cells. These findings suggest that enhanced glycolysis generally observed in cancer cells may be responsible for the radio-resistance, partly by enhancing the repair of DNA damage

  7. Enhanced radiation response in radioresistant MCF-7 cells by targeting peroxiredoxin II

    Directory of Open Access Journals (Sweden)

    Diaz AJG

    2013-10-01

    Full Text Available Anthony Joseph Gomez Diaz,1 Daniel Tamae,2 Yun Yen,3 JianJian Li,4 Tieli Wang1 1Department of Chemistry and Biochemistry, California State University at Dominguez Hills, Carson, CA, 2Center of Excellence in Environmental Toxicology, Department of Pharmacology, University of Pennsylvania, Philadelphia, PA, 3Department of Clinical and Molecular Pharmacology, Beckman Research Institute of City of Hope National Medical Center, Duarte, CA, 4Department of Radiation Oncology, University of California Davis, Sacramento, CA, USA Abstract: In our previous study, we identified that a protein target, peroxiredoxin II (PrxII, is overexpressed in radioresistant MCF+FIR3 breast-cancer cells and found that its expression and function is associated with breast-cancer radiation sensitivity or resistance. Small interference RNA (siRNA targeting PrxII gene expression was able to sensitize MCF+FIR3 radioresistant breast-cancer cells to ionizing radiation. The major focus of this work was to investigate how the radiation response of MCF+FIR3 radioresistant cells was affected by the siRNA that inhibits PrxII gene expression. Our results, presented here, show that silencing PrxII gene expression increased cellular toxicity by altering cellular thiol status, inhibiting Ca2+ efflux from the cells, and perturbing the intracellular Ca2+ homeostasis. By combining radiotherapy and siRNA technology, we hope to develop new therapeutic strategies that may have potential to enhance the efficacy of chemotherapeutic agents due to this technology's property of targeting to specific cancer-related genes. Keywords: siRNA, PrxII, radiation resistance, Ca2+, MCF+FIR3

  8. The heat shock proteins at the increasing of the radioresistance of silkworm embryo Bombyx Moril

    International Nuclear Information System (INIS)

    Agaev, F.A.; Garibov, A.A.; Aliev, D.I.; Alieva, I.N.

    2002-01-01

    The aim of this study is revealing the role of Heat Shock Proteins (HSP) at the radio-modification effect of Heat Shock (HS) on the silkworm embryo. Our preliminary study was indicated that 3-daily silkworm embryo is more than 10-12 times sensitive to gamma-radiation in comparative to 7-daily embryo. Investigation of the HS effect on the radiosensitivity of the embryo indicates that thermal treatment (40 deg. C) of 3 daily embryo during 60 min before irradiation leads the increasing of its radioresistance. At the same time, the HS treatment immediately after irradiation capable increases strike affect of irradiation. LD 50 for heat treated embryo before and after irradiation consists of 46.7 and 19.0 Gy, correspondingly. For embryo irradiated without heat treatment LD 50 is 29.5 Gy. Identical effects are observed for 7-daily embryo. Increasing of the radioresistance by HS before irradiation, obviously, may be explained by the embryo cell reply to the stress factor and capable initiated by different biochemical shifts, for example, by induction of HPS synthesis. According to the results of carried out experiments HS treatment leads to the induction or increasing of the HSP synthesis into this embryo. Protein with molecular mass 70 kDa (HSP-70 kDa) has been synthesised de novo. The synthesis of the other two proteins (HSP-83 kDa and HSP-68 kDa) significantly increases at the high temperature. It is noted, that HSP-70 kDa consists of 55-60 % of whole included radioactive mark. Identical induction was observed in the experiments at the combined effect both HS and gamma-radiation on the embryo. At the post-radiation heat treatment the induction of HSP synthesis is observed, too. It was concluded that damages induced by irradiation can not prevent HSP induction into embryo. The result of comparative analysis was shown that in 3-daily embryo in spite of 7-daily embryo the synthesis of HSP is more intensive and correlated with the radio- modification effect of HS. The

  9. Rate of oxygen consumption of hamster melanoma cells as a factor influencing their radioresistance

    International Nuclear Information System (INIS)

    Pajak, S.; Subczynski, W.; Panz, T.; Lukiewicz, S.

    1980-01-01

    It has been reported in recent years that the level of radiosensitivity of neoplasmic cells in vivo and of sphaeroids in vitro can be modified by controlling their rate of oxygen consumption. Thus, an attempt was made to compare this rate in the case of the melanotic and amelanotic lines of Bomirski hamster melanoma in vitro, as it is known that these two lines distinctly differ in their reactivity to ionizing radiations. The measurements carried out by the use of a new ESR method revealed that pigmented and pigmentless cells consume oxygen at significantly different rates. This means that oxygen utilization may contribute to the overall level of radioresistance of melanoma cells. (author)

  10. Alterations in radioresistance of eucaryotic cells after the transfer of genomic wildtype DNA and metallothionein genes

    International Nuclear Information System (INIS)

    Lohrer, H.

    1987-01-01

    The presented paper describes experiments concerning the alteration of radiosensitivity of eucaryotic cells after gene transfer. Ionizing radiation (γ- or X-ray) induces DNA single- or double strand breaks, which are religated by an unknown repair system. Repair deficient cells are highly sensitive to ionizing radiation. In the experiments described, cells from a patient with the heritable disease Ataxia telangiectasia were used as well as two X-ray sensitive CHO mutant cell lines. After gene transfer of an intact human DNA repair gene or a metallothionein gene the cells should regain radioresistance. (orig.) [de

  11. The increase in radioresistance of Chinese hamster cells cultured as spheroids is correlated to changes in nuclear morphology

    International Nuclear Information System (INIS)

    Gordon, D.J.; Milner, A.E.; Beaney, R.P.; Grdina, D.J.; Vaughan, A.T.

    1990-01-01

    Chinese hamster V79 cells grown as spheroids in roller culture are more radioresistant than those grown as monolayers. The supercoiled structure of chromatin, as salt-extracted nucleoids, has been examined using flow cytometry. Irradiated viable cells from spheroid culture contain restraints to supercoil relaxation that are absent in monolayer cells. Further analysis of the chromatin organization from each growth form shows that the radioresistant spheroid cells contain a DNA-protein matrix that is more resistant to detergent-induced degradation. The increase in structural integrity may be due to the retention of a 55-60 kDa protein that is apparent in the nucleoids of spheroid, but not monolayer cells. The increase in structural integrity of the spheroid cells may explain their greater radioresistance by providing a more stable platform for high-fidelity DNA damage repair

  12. Radioresistant CD4+ T cells in normal, unprimed mice, with verification of the Bergonie-Tribondeau law

    International Nuclear Information System (INIS)

    Makidono, Reiko; Ito, Akira.

    1997-01-01

    This is the first report on radioresistant CD4+ T cells found in normal, unprimed mice. After sublethal whole body irradiation, regular CD4+ as well as primitive NK1.1+ CD4+ T cells were enriched in the spleen. Since it has been well established that virgin T and B cells are highly radiosensitive, these cells were once assumed to be a unique lymphocyte population for which radiosensitivity does not follow the general law of radiation sensitivity for mammalian cells (Bergonie-Tribondeau law). These cells exhibited higher proliferative response to accessory cells than the non-irradiated control cells in the syngeneic mixed leukocyte reaction (SMLR). This indicated that virgin CD4+ T cells sensitized to, and readily respond to self-MHC class II molecules are radioresistant, and that their radioresistance, as activated cells, is consistent with the Bergonie-Tribondeau law. (author)

  13. Sister chromatid exchanges in X-ray irradiated blood lymphocytes from patients with hereditary diseases with radioresistant DNA synthesis

    International Nuclear Information System (INIS)

    Pleskach, N.M.; Andriadze, M.I.; Mikhel'son, V.M.; Zhestyanikov, V.D.

    1988-01-01

    X-ray irradiation induced sister chromatid exchanges (SCE) in blood lymphocytes from patient with Down's syndrome and adult progeria (in both the cases radioresistant DNA synthesis takes place). In normal lymphocytes (in which ionizing radiation inhibits the replicative synthesis of DNA) the rate of SCE rises with the rise of radiation dose. Thus, the rate of SCE in X-ray irradiated lymphocytes is in reverse dependence with radioresistance of replicative synthesis of DNA. The data obtained are explained in accordance with the replicative hypothesis of the SCE nature (Painter, 1980a): in cells of patients with Down's syndrome, xeroderma pigmentosum from 2 and progeria of adults the time of existence of partly replicated clusters of replicons is decreased due to radioresistant replicative synthesis of DNA, but the presence of partly replicated clusters of replicons in necessary for SCE formation. Therefore the rate of SCF in X-irradiated cells of these patients decreases

  14. Radioresistant cell strain of human fibrosarcoma cells obtained after long-term exposure to X-rays

    International Nuclear Information System (INIS)

    Wei, K.; Kodym, R.

    1998-01-01

    A radioresistant cell strain from human fibrosarcoma HT1080 has been obtained after prolonged exposure to x-rays for 7 months (2 Gy per day, 5 days per week). This new strain, HT1080R, differs from HT1080 in a significantly increased ability of clonogenical survival, with coefficient α decreasing from 0.161 to 0.123 Gy -1 and coefficient β decreasing from 0.0950 to 0.0565 Gy -2 . Furthermore, the radioresistance of HT1080R proved to be stable in long-term passaged cultures as well as in frozen samples. Differences between the two cell lines are also observed in the G-banded karyotype; the new cell line shows monosomy of chromosome 17 and loss of 5p + and 11q + present in the parental cells. These data suggest that the radioresistance may have been caused by radiation-induced cell mutation and that the resistant cells may have been selected by repeated irradiations. In order to characterize this new strain, the ability of the cells to rejoin DNA double-strand breaks, the cell cycle distribution and the amount of apoptosis after irradiation have been estimated; however, no differences are observed between these two cell strains. Although the mechanism of the elevated radioresistance remains unknown, this pair of cell strains can provide a new model system for further investigations with regard to the mechanisms of cellular radioresistance. The results also show that any type of irradiation similar to the schedules used in radiotherapy can lead to the formation and selection of more radioresistant cell clones in vitro, a phenomenon with possible implications for radiotherapy. (orig.)

  15. The effect of caffeine on x-ray repair of radioresistant HeLa cells

    International Nuclear Information System (INIS)

    Kubo, Kihei; Koiwai, Soichiro; Morita, Kazuo

    1985-01-01

    The contribution of caffeine-modifiable repair process to the radiosensitivity of a radioresistant HeLa strain (RC-355) has been investigated in comparison with control HeLa strain (CC-24). Both the final slope and the shoulder of X-ray survival curve for log-phase cells were affected by caffeine posttreatment. When the treatment with 10 mM caffeine delayed, an increase in survival was observed with increasing interval between irradiation and the treatment. During first several hours of the repair interval, the steepness of the final slope of survival curve decreased rapidly, and rate of the decrease was found to be higher in RC-355 than in CC-24 cells. Longer time (24 hours or more) before the initiation of caffeine treatment was required for the complete recovery of the shoulder. When the cells were incubated in plateau-phase after irradiation, an appreciable increase in survival was observed in comparison with when plated immediately following X-ray. The increase was found to be greater for RC-355 than for CC-24. The results suggest that the radioresistant RC-355 cells repaired more X-ray-induced PLD than CC-24 cells did. (author)

  16. Isolation and characterization of radioresistant mutants in Bacillus subtilis and Bacillus thuringiensis

    International Nuclear Information System (INIS)

    Kalinin, V.L.; Petrov, V.N.; Petrova, T.M.

    1981-01-01

    Vegetative cells of Bac. thuringiensis var. galleriae (the wild-type strain 351) are much more sensitive to lethal effects of UV light and 60 Co-γ-rays than those of Bac. subtilis (the wild-type strain 168). This difference is less pronounced for spores of these strains. By means of repeated γ-irradiation-regrowth cycles radioresistant mutants Bac. thuringiensis Gamsup(r) 14 and Bac. subtilis Gamsup(r) 9 were selected. The vegetative cells of these mutants are correspondingly 19 times and 3.9 times more resistant to lethal effects of γ-radiation than the cells of the parental strains. The resistance of the Gamsup(r) mutant cells to lethal effects of UV light and H 2 O 2 is also increased. The spores of the Gamsup(r) 14 mutant are 1.5-1.7 times more resistant to γ-radiation and UV light than the wild-type spores. The radioresistant mutants and the parental strains do not vary in their capacity for host-cell reactivation of UV- or γ-irradiated phages Tg13 and 105

  17. Potentially lethal damage repair in cell lines of radioresistant human tumours and normal skin fibroblasts

    International Nuclear Information System (INIS)

    Marchese, M.J.; Minarik, L.; Hall, E.J.; Zaider, M.

    1985-01-01

    Radiation cell survival data were obtained in vitro for three cell lines isolated from human tumours traditionally considered to be radioresistant-two melanomas and one osteosarcoma-as well as from a diploid skin fibroblast cell line. One melanoma cell line was much more radioresistant than the other, while the osteosarcoma and fibroblast cell lines were more radiosensitive than either. For cells growing exponentially, little potentially lethal damage repair (PLDR) could be demonstrated by comparing survival data for cells in which subculture was delayed by 6 h with those sub-cultured immediately after treatment. For the malignant cells in plateau phase, which in these cells might be better termed 'slowed growth phase', since an appreciable fraction of the cells are still cycling, a small amount of PLDR was observed, but not as much as reported by other investigators in the literature. The normal fibroblasts, which achieved a truer plateau phase in terms of noncycling cells, showed a significantly larger amount of PLDR than the tumour cells. (author)

  18. 9-β-arabinofuranosyladenine preferentially sensitizes radioresistant squamous cell carcinoma cell lines to x-rays

    International Nuclear Information System (INIS)

    Heaton, D.

    1992-06-01

    The effect of 9-β-arabinofuranosyladenine (ara-A) on sensitivity to the deleterious effects of x-rays was studied in six squamous cell carcinoma cell lines. Three lines were relatively radioresistant, having D 0 values of 2.31 to 2.89 Gy, and the other three lines were relatively radiosensitive, having D 0 values of between 1.07 and 1.45 Gy. Ara-A (50 or 500 μM) was added to cultures 30 min prior to irradiation and removed 30 min after irradiation, and sensitivity was measured in terms of cell survival. The radiosensitizing effect of ara-A was very dependent on the inherent radiosensitivity of the tumor cell line. Fifty micromolar concentrations of ara-A sensitized only the two most radioresistant lines, SCC-12B.2 and JSQ-3. Five hundred micromolar concentrations of ara-A sensitized the more sensitive cell lines, SQ-20B and SQ-9G, but failed to have any effect on the radiation response of the two most sensitive cell lines, SQ-38 and SCC-61. Concentrations of ara-A as low as 10 μM were equally efficient in inhibiting DNA synthesis in all six cell lines. These results suggest that the target for the radiosensitizing effect of ara-A is probably related to the factor controlling the inherent radiosensitivity of human tumor cells. Therefore, ara-A might be useful in overcoming radiation resistance in vivo

  19. 9-{beta}-arabinofuranosyladenine preferentially sensitizes radioresistant squamous cell carcinoma cell lines to x-rays

    Energy Technology Data Exchange (ETDEWEB)

    Heaton, D. [Rush Univ. Medical Center, Chicago, IL (United States). Therapeutic Radiology; Mustafi, R. [Chicago Univ., IL (United States). Dept. of Radiation and Cellular Oncology; Schwartz, J.L. [Chicago Univ., IL (United States). Dept. of Radiation and Cellular Oncology]|[Argonne National Lab., IL (United States)

    1992-06-01

    The effect of 9-{beta}-arabinofuranosyladenine (ara-A) on sensitivity to the deleterious effects of x-rays was studied in six squamous cell carcinoma cell lines. Three lines were relatively radioresistant, having D{sub 0} values of 2.31 to 2.89 Gy, and the other three lines were relatively radiosensitive, having D{sub 0} values of between 1.07 and 1.45 Gy. Ara-A (50 or 500 {mu}M) was added to cultures 30 min prior to irradiation and removed 30 min after irradiation, and sensitivity was measured in terms of cell survival. The radiosensitizing effect of ara-A was very dependent on the inherent radiosensitivity of the tumor cell line. Fifty micromolar concentrations of ara-A sensitized only the two most radioresistant lines, SCC-12B.2 and JSQ-3. Five hundred micromolar concentrations of ara-A sensitized the more sensitive cell lines, SQ-20B and SQ-9G, but failed to have any effect on the radiation response of the two most sensitive cell lines, SQ-38 and SCC-61. Concentrations of ara-A as low as 10 {mu}M were equally efficient in inhibiting DNA synthesis in all six cell lines. These results suggest that the target for the radiosensitizing effect of ara-A is probably related to the factor controlling the inherent radiosensitivity of human tumor cells. Therefore, ara-A might be useful in overcoming radiation resistance in vivo.

  20. Nicotine enhances proliferation, migration, and radioresistance of human malignant glioma cells through EGFR activation

    International Nuclear Information System (INIS)

    Khalil, A.A.; Jameson, M.J.; Broaddus, W.C.; Lin, P.S.; Chung, T.D.

    2013-01-01

    It has been suggested that continued tobacco use during radiation therapy contributes to maintenance of neoplastic growth despite treatment with radiation. Nicotine is a cigarette component that is an established risk factor for many diseases, neoplastic and otherwise. The hypothesis of this work is that nicotine promotes the proliferation, migration, and radioresistance of human malignant glioma cells. The effect of nicotine on cellular proliferation, migration, signaling, and radiation sensitivity were evaluated for malignant glioma U87 and GBM12 cells by use of the AlamarBlue, scratch healing, and clonogenic survival assays. Signal transduction was assessed by immunoblotting for activated EGFR, extracellular regulated kinase (ERK), and AKT. At concentrations comparable with those found in chronic smokers, nicotine induced malignant glioma cell migration, growth, colony formation, and radioresistance. Nicotine increased phosphorylation of EGFR tyr992 , AKT ser473 , and ERK. These molecular effects were reduced by pharmacological inhibitors of EGFR, PI3K, and MEK. It was therefore concluded that nicotine stimulates the malignant behavior of glioma cells in vitro by activation of the EGFR and downstream AKT and ERK pathways. (author)

  1. Radioresistant DNA synthesis in cells of patients showing increased chromosomal sensitivity to ionizing radiation

    International Nuclear Information System (INIS)

    Barenfeld, L.S.; Pleskach, N.M.; Bildin, V.N.; Prokofjeva, V.V.; Mikhelson, V.M.

    1986-01-01

    The rate of DNA synthesis after γ-irradiation was studied either by analysis of the steady-state distribution of daughter [ 3 H]DNA in alkaline sucrose gradients or by direct assay of the amount of [ 3 H]thymidine incorporated into DNA of fibroblasts derived from a normal donor (LCH882) and from Down's syndrome (LCH944), Werner's syndrome (WS1LE) and xeroderma pigmentosum (XP2LE) patients with chromosomal sensitivity to ionizing radiation. Doses of γ-irradiation that markedly inhibited the rate of DNA synthesis in normal human cells caused almost no inhibition of DNA synthesis in the cells from the affected individuals. The radioresistant DNA synthesis in Down's syndrome cells was mainly due to a much lower inhibition of replicon initiation than that in normal cells; these cells were also more resistant to damage that inhibited replicon elongation. Our data suggest that radioresistant DNA synthesis may be an intrinsic feature of all genetic disorders showing increased radiosensitivity in terms of chromosome aberrations. (orig.)

  2. Selection of radioresistant cells by vitamin A deficiency in a small cell lung cancer cell line

    International Nuclear Information System (INIS)

    Terasaki, Takeo; Shimosato, Yukio; Wada, Makio; Yokota, Jun; Terada, Masaaki

    1990-01-01

    Radiation sensitivity of a human small cell lung cancer cell line, Lu-134-B cells, cultured in serum-supplemented medium and of cells transferred to and cultured in delipidized serum-supplemented (vitamin A-deficient) medium was studied. The cells cultured in serum-supplemented medium showed the phenotype of classic small cell lung cancer sensitive to radiation, while cells transferred to delipidized serum-supplemented medium showed partial squamous cell differentiation and became resistant to radiation. These results suggest that some small cell lung cancer cells in vitro change their morphology and radiosensitivity depending on the culture conditions. The change in radiosensitivity was reproducible, and was not reversible by culture of the radioresistant cells in delipidized serum-supplemented medium with addition of retinoic acid (vitamin A-sufficient medium) for two months, although squamous cells disappeared. Acquisition of radioresistancy was considered to occur as the result of clonal selective growth in delipidized medium of a minor cell population in the original cell culture, based on a study of chromosome number. It was also found that there was no association of myc-family oncogenes with the changes of radiosensitivity in this cell line. (author)

  3. Reprogramming mediated radio-resistance of 3D-grown cancer cells

    International Nuclear Information System (INIS)

    Xue Gang; Ren Zhenxin; Chen Yaxiong; Zhu Jiayun; Du Yarong; Pan Dong; Li Xiaoman; Hu Burong; Grabham, Peter W.

    2015-01-01

    In vitro 3D growth of tumors is a new cell culture model that more closely mimics the features of the in vivo environment and is being used increasingly in the field of biological and medical research. It has been demonstrated that cancer cells cultured in 3D matrices are more radio-resistant compared with cells in monolayers. However, the mechanisms causing this difference remain unclear. Here we show that cancer cells cultured in a 3D microenvironment demonstrated an increase in cells with stem cell properties. This was confirmed by the finding that cells in 3D cultures upregulated the gene and protein expression of the stem cell reprogramming factors such as OCT4, SOX2, NANOG, LIN28 and miR-302a, compared with cells in monolayers. Moreover, the expression of β-catenin, a regulating molecule of reprogramming factors, also increased in 3D-grown cancer cells. These findings suggest that cancer cells were reprogrammed to become stem cell-like cancer cells in a 3D growth culture microenvironment. Since cancer stem cell-like cells demonstrate an increased radio-resistance and chemo-resistance, our results offer a new perspective as to why. Our findings shed new light on understanding the features of the 3D growth cell model and its application in basic research into clinical radiotherapy and medicine. (author)

  4. Establishment and cell cycle distribution pattern of a radioresistant subline from human lung cancer D6 cell line

    International Nuclear Information System (INIS)

    Wei Qichun; Zheng Shu

    2003-01-01

    Objective: To establish a radioresistant cell subline from a human D6 lung cancer cell line and investigate the mechanism of radioresistance. Methods: D6 human NSCLC cells were exposed to X-rays generated by a linear accelerator(650 cGy per fraction). After a total exposure dose of 5200 cGy, a monoclone was obtained. The radiosensitivity and cell cycle distribution of this clone, together with its parent D6 cells, were measured by clonogenic assay and flow cytometry. Results: The new clone, namely D 6 -R subline, had a higher D 0 (D 0 =2.08 Gy) and a broader initial shoulder(Dq=1.64 Gy, N=2.20) than those of the parent D6 cell line (D 0 =1.84 Gy, Dq=0.34 Gy, N=1.20), being 1.65-fold increase in radioresistance as regards to the SF 2 . The D6-R subline also showed higher percentage of cells in S phase(53.4% vs 37.8%), but lower percentages in G 1 (44.1% vs 57.2%) and G 2 /M(2.5% vs 5%) phases. Conclusion: The new subline D6-R is more radioresistant as compare to its parent D6 cell line, and has a different cell cycle distribution

  5. The repair/repopulation effects ratio in the postirradiation recovery of hexaploid wheat varieties contrast by their radioresistance

    International Nuclear Information System (INIS)

    Selezneva, E.M.; Sarapul'tsev, B.I.

    1988-01-01

    The cytogenic and morphometrical distinctions between hexaploid wheat varieties contrast by their radioresistance during the postirradiation period are attributed to the differential activity of caffeine-dependent repair processes; they are not a reliable function of the rate of aberrant cell elimination

  6. The phosphatidylinositol-3 kinase pathway is not essential for insulin-like growth factor I receptor-mediated clonogenic radioresistance

    International Nuclear Information System (INIS)

    Yu, Dong; Watanabe, Hiroshi; Shibuya, Hitoshi; Miura, Masahiko

    2002-01-01

    The insulin-like growth factor I receptor (IGF-IR) is known to induce clonogenic radioresistance in cells following ionizing irradiation. To explore the downstream signaling pathways, we focused on the phosphatidylinositol-3 kinase (PI3-K) pathway, which is thought to be the primary cell survival signal originating from the receptor. For this purpose, R- cells deficient in the endogenous IGF-IR were used as a recipient of the human IGF-IR with or without mutations at potential PI3-K activation sites: NPXY 950 and Y 1316 XXM. Mutats with double mutation at Y950/Y1316 exhibited not abrogated, but reduced activation of insulin receptor substance-1 (IRS-1), PI3-K, and Akt upon IGF-I stimulation. However, the mutants had the same clonogenic radioresistance as cells with wild type (WT) receptors. Neither wortmannin nor LY294002, specific inhibitors of PI3-K, affected the radioresistance of cells with WT receptors at concentrations specific for PI3-K. Collectively, these results indicate that the PI3-K pathway is not essential for IGF-IR-mediated clonogenic radioresistance. (author)

  7. Dexamethasone-induced radioresistance occurring independent of human papilloma virus gene expression in cervical carcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Rutz, H.P.; Mariotta, M.; Mirimanoff, R.O. [Lab. de Radiobiologie, Service de Radio-Oncologie, CHUV, Lausanne (Switzerland); Knebel Doeberitz, M. von [Deutsches Krebsforschungszentrum, Heidelberg (Germany). Inst. fuer Virusforschung

    1998-02-01

    The aim of this study was to investigate the role of HPV 18 E6 and E7 gene products with respect to radiosensitivity of two cervical carcinoma cell lines. The two cervical carcinoma lines C4-1 and SW 756 were used in which treatment with dexamethasone allows to modulate expression levels of HPV 18 E6 and E7 genes: Upregulation in C4-1, down-regulation in SW 756. Effects of treatment with dexamethasone on plating efficiency and radiosensitivity were assessed using a clonogenic assay. Treatment with dexamethasone increased plating efficiency of the C4-1 cells, but did not affect plating efficiency of SW 756 cells. Treatment with dexamethasone induced enhanced radioresistance in both cell lines. Thus, in C4-1 cells the observed changes in radioresistance correlate to the enhancement in expression of HPV 18 genes E6/E7, whereas in SW 756, a reduced expression correlates negatively with the enhanced radioresistance. (orig./MG) [Deutsch] Das Ziel dieser Studie lag darin, die Rolle der HPV-18-Gene E6 und E7 in bezug auf die Strahlenempfindlichkeit von menschlichen Zervixkarzinomzellen zu untersuchen. Wir verwendeten zwei menschliche Zervixkarzinomzellinien, C4-1 und SW 756, in welchen die Expression der viralen Gene HPV 18 E6 und E7 mit Dexamethason moduliert werden kann: In C4-1 bewirkt die Behandlung mit Dexamethason eine Erhoehung der Expression dieser Gene, in SW 756 eine Verminderung. Die Wirkung auf die Wachstumsfaehigkeit der Zellen und auf die Wachstumshemmung durch die Bestrahlung wurde unter Verwendung eines klonogenen Assays bestimmt. Dexamethason bewirkte eine erhoehte Wachstumsfaehigkeit der C4-1 Zellen, ohne die Wachstumsfaehigkeit der SW-756-Zellen zu beeinflussen, wie schon frueher beschrieben. Die Resistenz beider Zellinien gegenueber Bestrahlung wurde erhoeht. Somit besteht in den C4-1-Zellen eine Korrelation der Expression der viralen Gene mit der Zunahme der Strahlenresistenz, wogegen in den SW-756-Zellen die Abnahme der Expression im Gegensatz zu

  8. Radioresponsiveness at low doses. Hyper-radiosensitivity and increased radioresistance in mammalian cells

    International Nuclear Information System (INIS)

    Skov, K.A.

    1999-01-01

    The rationale for and importance of research on effects after radiation at 'low doses' are outlined. Such basic radiobiological studies on induction of repair enzymes, protective mechanisms, priming, and hypersensitivity are certainly all relevant to treatment of cancer (see Section 1, Studies at low doses - relevance to cancer treatment). Included are examples from many groups, using various endpoints to address the possibility of an induced resistance, which has been compared to the adaptive response [M.C. Joiner, P. Lambin, E.P. Malaise, T. Robson, J.E. Arrand, K.A. Skov, B. Marples, Hypersensitivity to very low single radiation doses: its relationship to the adaptive response and induced radioresistance, Mutat. Res. 358 (1996) 171-183.]. This is not intended to be an exhaustive review - rather a re-introduction of concepts such as priming and a short survey of molecular approaches to understanding induced resistance. New data on the response of HT29 cells after treatment (priming) with co-cultured activated neutrophils are included, with protection against X-rays (S1). Analysis of previously published results in various cells lines in terms of increased radioresistance (IRR)/intrinsic sensitivity are presented which complement a study on human tumour lines [P. Lambin, E.P. Malaise, M.C. Joiner, Might intrinsic radioresistance of human tumour cells be induced by radiation?, Int. Radiat. Biol. 69 (1996) 279-290]. It is not feasible to extrapolate to low doses from studies at high doses. The biological responses probably vary with dose, LET, and have variable time frames. The above approaches may lead to new types of treatment, or additional means to assess radioresponsiveness of tumours. Studies in many areas of biology would benefit from considerations of different dose regions, as the biological responses vary with dose. There may also be some implications in the fields of radiation protection and carcinogenesis, and the extensions of concepts of hyper

  9. Activation of mitochondrial promoter PH-binding protein in a radio-resistant Chinese hamster cell strain associated with Bcl-2

    International Nuclear Information System (INIS)

    Roychoudhury, Paromita; Ghosh, Utpal; Bhattacharyya, Nitai P.; Chaudhuri, Keya

    2006-01-01

    The cellular response to ionizing radiation is mediated by a complex interaction of number of proteins involving different pathways. Previously, we have shown that up regulation of mitochondrial genes ND1, ND4, and COX1 transcribed from the heavy strand promoter (P H ) has been increased in a radio-resistant cell strain designated as M5 in comparison with the parental Chinese hamster V79 cells. These genes are also up regulated in Chinese hamster V79 cells VB13 that express exogenous human Bcl2. In the present study, the expression of the gene ND6 that is expressed from the light strand promoter (P L ) was found to be similar in both the cell lines, as determined by RT-PCR. To test the possibility that this differential expression of mitochondrial genes under these two promoters was mediated by differences in proteins' affinity to interact with these promoters, we have carried out electrophoretic mobility shift assay (EMSA) using mitochondrial cell extracts from these two cell lines. Our result of these experiments revealed that two different proteins formed complex with the synthetic promoters and higher amount of protein from M5 cell extracts interacted with the P H promoter in comparison to that observed with cell extracts from Chinese hamster V79 cells. The promoter-specific differential binding of proteins was also observed in VB13. These results showed that differential mitochondrial gene expression observed earlier in the radio-resistant M5 cells was due to enhanced interaction proteins with the promoters P H and mediated by the expression of Bcl2

  10. HIF-1α inhibition by siRNA or chetomin in human malignant glioma cells: effects on hypoxic radioresistance and monitoring via CA9 expression

    Directory of Open Access Journals (Sweden)

    Bache Matthias

    2010-11-01

    Full Text Available Abstract Background Hypoxia induces activation of the HIF-1 pathway and is an essential characteristic of malignant gliomas. Hypoxia has been linked to tumor progression, therapy resistance and poor prognosis. However, little is known about the impact of HIF-1α inhibition on radioresistance of malignant glioma. Methods In this study, we investigated the effects of the inhibition of HIF-1α on cell survival and radiosensitivity in U251MG and U343MG glioma cells, using two different strategies. HIF-1α inhibition was achieved by siRNA targeting of HIF-1α or via chetomin, a disruptor of interactions between HIF-1α and p300. The inhibition of the HIF-1 pathway was monitored by quantitative real-time PCR and Western blot analyses of the expression levels of HIF-1α and CA9. CA9 expression was investigated as a potential indicator of the efficacy of HIF-1 inhibition and the resulting radiosensitivity of malignant glioma cell lines was determined by clonogenic assay after irradiation under normoxic (2-10 Gy or hypoxic (2-15 Gy conditions. Results Although siRNA and chetomin show distinct modes of action, both attenuated the hypoxia-induced radioresistance of malignant glioma cell lines U251MG (DMF10: 1.35 and 1.18 and U343MG (DMF10: 1.78 and 1.48. However, siRNA and chetomin showed diverse effects on radiosensitivity under normoxic conditions in U251MG (DMF10: 0.86 and 1.35 and U343MG (DMF10: 1.33 and 1.02 cells. Conclusions Results from this in vitro study suggest that inhibition of HIF-1α is a promising strategy to sensitize human malignant gliomas to radiotherapy and that CA9 could serve as an indicator of effective HIF-1-related radiosensitization.

  11. Radioresistant DNA synthesis in fibroblasts of a patient with Down's syndrome

    International Nuclear Information System (INIS)

    Barenfel'd, L.S.; Bil'din, V.N.; Pleskach, N.M.; Prokof'eva, V.V.

    1985-01-01

    Ionizing radiation effect on DNA replication on fibroblasts of a healthy donor and a patient with Down's syndrome either by direct 3 H-thymidine inclusion into DNA, or by analysis of the sizes of daughter DNA moleculs at the state of stable distribution in acid saccharose, gradients was studied. Gamma-radiation doses (5-10 Gy) suppressing DNA synthesis in normal fibroblasts practically had no effect on DNA synthesisin fibroblasts of a patient with Down's syndrome. Radioresistant DNA synthesis in Down's syndrome is conditioned by a far less supression of replicon initiation as compared with the one in normal cells. So, it is stated that in Down's disease there is no delay in DNA synthesis by ionizing radiation that enables the normal cells to repair DNA damages before replication renewal

  12. Investigations on radiosensitive and radioresistant populations of Drosophila melanogaster. Pt. 10

    International Nuclear Information System (INIS)

    Noethel, H.

    1981-01-01

    In earlier work, immature oocytes of the irradiated population RoeI 4 of Drosophila melanogaster were found to be radioresistant relative to those of the basic population RoeI and to those of the control population Berlin wild (+K). The resistance of RoeI 4 relative to RoeI was previously attributed to a hypothetical 'factor' rar-3. In the present paper, evidence is presented to show that rar-3 is a single, recessive genetic factor, located on chromosome 3 at a map position of about 49.8. The action of rar-3 is apparently independent of that of rar-1 and rar-2, the factors already present in RoeI. (orig.)

  13. Targeting the AKT/GSK3β/Cyclin D1/Cdk4 Survival Signaling Pathway for Eradication of Tumor Radioresistance Acquired by Fractionated Radiotherapy

    International Nuclear Information System (INIS)

    Shimura, Tsutomu; Kakuda, Satoshi; Ochiai, Yasushi; Kuwahara, Yoshikazu; Takai, Yoshihiro; Fukumoto, Manabu

    2011-01-01

    Purpose: Radioresistance is a major cause of treatment failure of radiotherapy (RT) in human cancer. We have recently revealed that acquired radioresistance of tumor cells induced by fractionated radiation is attributable to cyclin D1 overexpression as a consequence of the downregulation of GSK3β-dependent cyclin D1 proteolysis mediated by a constitutively activated serine-threonine kinase, AKT. This prompted us to hypothesize that targeting the AKT/GSK3β/cyclin D1 pathway may improve fractionated RT by suppressing acquired radioresistance of tumor cells. Methods and Materials: Two human tumor cell lines with acquired radioresistance were exposed to X-rays after incubation with either an AKT inhibitor, AKT/PKB signaling inhibitor-2 (API-2), or a Cdk4 inhibitor (Cdk4-I). Cells were then subjected to immunoblotting, clonogenic survival assay, cell growth analysis, and cell death analysis with TUNEL and annexin V staining. In vivo radiosensitivity was assessed by growth of human tumors xenografted into nude mice. Results: Treatment with API-2 resulted in downregulation of cyclin D1 expression in cells with acquired radioresistance. Cellular radioresistance disappeared completely both in vitro and in vivo with accompanying apoptosis when treated with API-2. Furthermore, inhibition of cyclin D1/Cdk4 by Cdk4-I was sufficient for abolishing radioresistance. Treatment with either API-2 or Cdk4-I was also effective in suppressing resistance to cis-platinum (II)-diamine-dichloride in the cells with acquired radioresistance. Interestingly, the radiosensitizing effect of API-2 was canceled by overexpression of cyclin D1 whereas Cdk4-I was still able to sensitize cells with cyclin D1 overexpression. Conclusion: Cyclin D1/Cdk4 is a critical target of the AKT survival signaling pathway responsible for tumor radioresistance. Targeting the AKT/GSK3β/cyclin D1/Cdk4 pathway would provide a novel approach to improve fractionated RT and would have an impact on tumor eradication in

  14. Metabolic analysis of radioresistant medulloblastoma stem-like clones and potential therapeutic targets.

    Directory of Open Access Journals (Sweden)

    Lue Sun

    Full Text Available Medulloblastoma is a fatal brain tumor in children, primarily due to the presence of treatment-resistant medulloblastoma stem cells. The energy metabolic pathway is a potential target of cancer therapy because it is often different between cancer cells and normal cells. However, the metabolic properties of medulloblastoma stem cells, and whether specific metabolic pathways are essential for sustaining their stem cell-like phenotype and radioresistance, remain unclear. We have established radioresistant medulloblastoma stem-like clones (rMSLCs by irradiation of the human medulloblastoma cell line ONS-76. Here, we assessed reactive oxygen species (ROS production, mitochondria function, oxygen consumption rate (OCR, energy state, and metabolites of glycolysis and tricarboxylic acid cycle in rMSLCs and parental cells. rMSLCs showed higher lactate production and lower oxygen consumption rate than parental cells. Additionally, rMSLCs had low mitochondria mass, low endogenous ROS production, and existed in a low-energy state. Treatment with the metabolic modifier dichloroacetate (DCA resulted in mitochondria dysfunction, glycolysis inhibition, elongated mitochondria morphology, and increased ROS production. DCA also increased radiosensitivity by suppression of the DNA repair capacity through nuclear oxidization and accelerated the generation of acetyl CoA to compensate for the lack of ATP. Moreover, treatment with DCA decreased cancer stem cell-like characters (e.g., CD133 positivity and sphere-forming ability in rMSLCs. Together, our findings provide insights into the specific metabolism of rMSLCs and illuminate potential metabolic targets that might be exploited for therapeutic benefit in medulloblastoma.

  15. Cyclophilin B Expression Is Associated with In Vitro Radioresistance and Clinical Outcome after Radiotherapy

    Directory of Open Access Journals (Sweden)

    Paul D. Williams

    2011-12-01

    Full Text Available The tools for predicting clinical outcome after radiotherapy are not yet optimal. To improve on this, we applied the COXEN informatics approach to in vitro radiation sensitivity data of transcriptionally profiled human cells and gene expression data from untreated head and neck squamous cell carcinoma (HNSCC and bladder tumors to generate a multigene predictive model that is independent of histologic findings and reports on tumor radiosensitivity. The predictive ability of this 41-gene model was evaluated in patients with HNSCC and was found to stratify clinical outcome after radiotherapy. In contrast, this model was not useful in stratifying similar patients not treated with radiation. This led us to hypothesize that expression of some of the 41 genes contributes to tumor radioresistance and clinical recurrence. Hence, we evaluated the expression the 41 genes as a function of in vitro radioresistance in the NCI-60 cancer cell line panel and found cyclophilin B (PPIB, a peptidylprolyl isomerase and target of cyclosporine A (CsA, had the strongest direct correlation. Functional inhibition of PPIB by small interfering RNA depletion or CsA treatment leads to radiosensitization in cancer cells and reduced cellular DNA repair. Immunohistochemical evaluation of PPIB expression in patients with HNSCC was found to be associated with outcome after radiotherapy. This work demonstrates that a novel 41-gene expression model of radiation sensitivity developed in bladder cancer cell lines and human skin fibroblasts predicts clinical outcome after radiotherapy in head and neck cancer patients and identifies PPIB as a potential target for clinical radiosensitization.

  16. Inhibition of GRP78 abrogates radioresistance in oropharyngeal carcinoma cells after EGFR inhibition by cetuximab.

    Directory of Open Access Journals (Sweden)

    Chaonan Sun

    Full Text Available The EGFR-specific mAb cetuximab is one of the most effective treatments for oropharyngeal carcinoma, while patient responses to EGFR inhibitors given alone are modest. Combination treatment with radiation can improve the efficacy of treatment through increasing radiosensitivity, while resistance to radiation after administration of cetuximab limits its efficiency. Radiation and drugs can damage the endoplasmic reticulum (ER homeostatic state and result in ER stress (ERS, subsequently causing resistance to radiation and drugs. Whether the ERS pathway is involved in radioresistance after administration of cetuximab has not been reported. Herein, we show that cetuximab could increase the radiosensitivity of FaDu cells but not Detroit562 cells. In addition, cetuximab inhibited the radiation-induced activation of the ERS signalling pathway IRE1α/ATF6-GRP78 in FaDu cells, while this effect was absent in Detroit562 cells. Silencing GRP78 increased the radiosensitivity of oropharyngeal carcinoma cells and inhibited radiation-induced DNA double-strand-break (DSB repair and autophagy. More interestingly, silencing GRP78 abrogated resistance to cetuximab and radiation in Detroit562 cells and had a synergistic effect with cetuximab in increasing the radiosensitivity of FaDu cells. Immunohistochemistry showed that overexpression of both GRP78 and EGFR was associated with a poor prognosis in oropharyngeal carcinoma patients (P<0.05. Overall, the results of this study show that radioresistance after EGFR inhibition by cetuximab is mediated by the ERS signalling pathway IRE1α/ATF6-GRP78. This suppression was consequently unable to inhibit radiation-induced DSB repair and autophagy in oropharyngeal carcinoma cells, which conferred resistance to radiotherapy and cetuximab. These results suggest that the cooperative effects of radiotherapy and cetuximab could be further improved by inhibiting GRP78 in non-responsive oropharyngeal carcinoma patients.

  17. Mechanism of derivation of radioresistance in HeLa cell population after repeated x-irradiation

    International Nuclear Information System (INIS)

    Kubo, Kihei; Koiwai, Soichiro; Morita, Kazuo

    1982-01-01

    The Radioresistant strain (X-8-5) was obtained from HeLa-SC population X-irradiated repeatedly for five times with 800 rad. The mean lethal dose (D 0 ) was 196 rad for X-8-5 cells, while it was 166 rad for control HeLa-SC cells. The fraction of cells containing an unusually long acrocentric chromosome (LA 2) exclusively increased with increasing number of irradiation of HeLa-SC population. A clonal strain with LA 2 marker was isolated from X-8-5 population and named RC-355. Since the RC-355 cells were more resistant (D 0 = 220 rad)than parental X-8-5 cells (D 0 = 196 rad), it was suggested that the cells with LA 2 were responsible for the radioresistance of X-8-5 population. The RC-355 cells were further subjected to the analysis of Q-banded karyotypes and it was observed that 18 types of specific markers (rm 1-17 and LA 2) were included in RC-355 cells in addition to 12 types of markers observed in most of HeLa-SC cells. Since the analysis of Q-banded karyotypes of RC-355 cells showed that RC-355 specific markers were not produced by radiation-induced rearrangements of HeLa-SC chromosomes, because twelve kinds of HeLa-SC markers were presented in RC-355 cells without any change, it was concluded that a small number of cells with LA 2 marker were originally presented in the control population and the relative fraction of them occupied increased after irradiation. (author)

  18. Association of anti-apoptotic Mcl-1L isoform expression with radioresistance of oral squamous carcinoma cells

    International Nuclear Information System (INIS)

    Palve, Vinayak C; Teni, Tanuja R

    2012-01-01

    Oral cancer is a common cancer and a major health problem in the Indian subcontinent. At our laboratory Mcl-1, an anti-apoptotic member of the Bcl-2 family has been demonstrated to be overexpressed in oral cancers and to predict outcome in oral cancer patients treated with definitive radiotherapy. To study the role of Mcl-1 isoforms in radiation response of oral squamous carcinoma cells (OSCC), we investigated in the present study, the association of Mcl-1 isoform expression with radiosensitivity of OSCC, using siRNA strategy. The time course expression of Mcl-1 splice variants (Mcl-1L, Mcl-1S & Mcl-1ES) was studied by RT-PCR, western blotting & immunofluorescence, post-irradiation in oral cell lines [immortalized FBM (radiosensitive) and tongue cancer AW8507 & AW13516 (radioresistant)]of relatively differing radiosensitivities. The effect of Mcl-1L knockdown alone or in combination with ionizing radiation (IR) on cell proliferation, apoptosis & clonogenic survival, was investigated in AW8507 & AW13516 cells. Further the expression of Mcl-1L protein was assessed in radioresistant sublines generated by fractionated ionizing radiation (FIR). Three to six fold higher expression of anti-apoptotic Mcl-1L versus pro-apoptotic Mcl-1S was observed at mRNA & protein levels in all cell lines, post-irradiation. Sustained high levels of Mcl-1L, downregulation of pro-apoptotic Bax & Bak and a significant (P < 0.05) reduction in apoptosis was observed in the more radioresistant AW8507, AW13516 versus FBM cells, post-IR. The ratios of anti to pro-apoptotic proteins were high in AW8507 as compared to FBM. Treatment with Mcl-1L siRNA alone or in combination with IR significantly (P < 0.01) increased apoptosis viz. 17.3% (IR), 25.3% (siRNA) and 46.3% (IR plus siRNA) and upregulated pro-apoptotic Bax levels in AW8507 cells. Combination of siRNA & IR treatment significantly (P < 0.05) reduced cell proliferation and clonogenic survival of radioresistant AW8507 & AW13516 cells

  19. Genome-wide analyses of long noncoding RNA expression profiles correlated with radioresistance in nasopharyngeal carcinoma via next-generation deep sequencing.

    Science.gov (United States)

    Li, Guo; Liu, Yong; Liu, Chao; Su, Zhongwu; Ren, Shuling; Wang, Yunyun; Deng, Tengbo; Huang, Donghai; Tian, Yongquan; Qiu, Yuanzheng

    2016-09-06

    Radioresistance is one of the major factors limiting the therapeutic efficacy and prognosis of patients with nasopharyngeal carcinoma (NPC). Accumulating evidence has suggested that aberrant expression of long noncoding RNAs (lncRNAs) contributes to cancer progression. Therefore, here we identified lncRNAs associated with radioresistance in NPC. The differential expression profiles of lncRNAs associated with NPC radioresistance were constructed by next-generation deep sequencing by comparing radioresistant NPC cells with their parental cells. LncRNA-related mRNAs were predicted and analyzed using bioinformatics algorithms compared with the mRNA profiles related to radioresistance obtained in our previous study. Several lncRNAs and associated mRNAs were validated in established NPC radioresistant cell models and NPC tissues. By comparison between radioresistant CNE-2-Rs and parental CNE-2 cells by next-generation deep sequencing, a total of 781 known lncRNAs and 2054 novel lncRNAs were annotated. The top five upregulated and downregulated known/novel lncRNAs were detected using quantitative real-time reverse transcription-polymerase chain reaction, and 7/10 known lncRNAs and 3/10 novel lncRNAs were demonstrated to have significant differential expression trends that were the same as those predicted by deep sequencing. From the prediction process, 13 pairs of lncRNAs and their associated genes were acquired, and the prediction trends of three pairs were validated in both radioresistant CNE-2-Rs and 6-10B-Rs cell lines, including lncRNA n373932 and SLITRK5, n409627 and PRSS12, and n386034 and RIMKLB. LncRNA n373932 and its related SLITRK5 showed dramatic expression changes in post-irradiation radioresistant cells and a negative expression correlation in NPC tissues (R = -0.595, p < 0.05). Our study provides an overview of the expression profiles of radioresistant lncRNAs and potentially related mRNAs, which will facilitate future investigations into the

  20. Microarray analysis of DNA damage repair gene expression profiles in cervical cancer cells radioresistant to 252Cf neutron and X-rays

    International Nuclear Information System (INIS)

    Qing, Yi; Wang, Ge; Wang, Dong; Yang, Xue-Qin; Zhong, Zhao-Yang; Lei, Xin; Xie, Jia-Yin; Li, Meng-Xia; Xiang, De-Bing; Li, Zeng-Peng; Yang, Zhen-Zhou

    2010-01-01

    The aim of the study was to obtain stable radioresistant sub-lines from the human cervical cancer cell line HeLa by prolonged exposure to 252 Cf neutron and X-rays. Radioresistance mechanisms were investigated in the resulting cells using microarray analysis of DNA damage repair genes. HeLa cells were treated with fractionated 252 Cf neutron and X-rays, with a cumulative dose of 75 Gy each, over 8 months, yielding the sub-lines HeLaNR and HeLaXR. Radioresistant characteristics were detected by clone formation assay, ultrastructural observations, cell doubling time, cell cycle distribution, and apoptosis assay. Gene expression patterns of the radioresistant sub-lines were studied through microarray analysis and verified by Western blotting and real-time PCR. The radioresistant sub-lines HeLaNR and HeLaXR were more radioresisitant to 252 Cf neutron and X-rays than parental HeLa cells by detecting their radioresistant characteristics, respectively. Compared to HeLa cells, the expression of 24 genes was significantly altered by at least 2-fold in HeLaNR cells. Of these, 19 genes were up-regulated and 5 down-regulated. In HeLaXR cells, 41 genes were significantly altered by at least 2-fold; 38 genes were up-regulated and 3 down-regulated. Chronic exposure of cells to ionizing radiation induces adaptive responses that enhance tolerance of ionizing radiation and allow investigations of cellular radioresistance mechanisms. The insights gained into the molecular mechanisms activated by these 'radioresistance' genes will lead to new therapeutic targets for cervical cancer

  1. β‑catenin nuclear translocation induced by HIF‑1α overexpression leads to the radioresistance of prostate cancer.

    Science.gov (United States)

    Luo, Yong; Li, Mingchuan; Zuo, Xuemei; Basourakos, Spyridon P; Zhang, Jiao; Zhao, Jiahui; Han, Yili; Lin, Yunhua; Wang, Yongxing; Jiang, Yongguang; Lan, Ling

    2018-04-12

    Hypoxia-inducible factor‑1α (HIF‑1α) is known to play crucial roles in tumor radioresistance; however, the molecular mechanisms responsible for the promotion of tumor radioresistance by HIF‑1α remain unclear. β‑catenin is known to be involved in the metastatic potential of prostate cancer (PCa). In this study, to investigate the role of HIF‑1α and β‑catenin in the radioresistance of PCa, two PCa cell lines, LNCaP and C4‑2B, were grouped as follows: Negative control (no treatment), HIF‑1α overexpression group (transfected with HIF‑1α overexpression plasmid) and β‑catenin silenced group (transfected with HIF‑1α plasmids and β‑catenin-shRNA). Cell proliferation, cell cycle, cell invasion and radiosensitivity were examined under normal or hypoxic conditions. In addition, radiosensitivity was examined in two mouse PCa models (the LNCaP orthotopic BALB/c-nu mice model and the C4‑2B subcutaneous SCID mice model). Our results revealed that in both the LNCaP and C4‑2B cells, transfection with HIF‑1α overexpression plasmid led to an enhanced β‑catenin nuclear translocation, while β‑catenin silencing inhibited β‑catenin nuclear translocation. The enhanced β‑catenin nuclear translocation induced by HIF‑1α overexpression resulted in an enhanced cell proliferation and cell invasion, an altered cell cycle distribution, decreased apoptosis, and improved non‑homologous end joining (NHEJ) repair under normal and irradiation conditions. Similar results were observed in the animal models. HIF‑1α overexpression enhanced β‑catenin nuclear translocation, which led to the activation of the β‑catenin/NHEJ signaling pathway and increased cell proliferation, cell invasion and DNA repair. These results thus suggest that HIF‑1α overexpression promotes the radioresistance of PCa cells.

  2. A comparative study of radioresistance of rare and non-disappearing species of tulipal from the flora of Azerbaijan

    International Nuclear Information System (INIS)

    Ibadov, O.V.; Askerov, I.T.; Medzhidov, M.M.; Alekperov, U.K.

    1983-01-01

    Eichle and Sclimid bulds irradiated by gamma-rays of different doses (1-1 Gy) have been investigated. Morphological and phenological observations are carried out, decorative propertie the tested plants are estimated. It is found that low radiation doses (1-5 Gy) stimulate the sprouting of these species, while high doses suppress it. The Eichler species being somewhat more radioresistant than those of Schmi type

  3. In vitro stemness characterization of radio-resistant clones isolated from a medulloblastoma cell line ONS-76

    International Nuclear Information System (INIS)

    Sun, Lue; Suzuki, Kenshi; Gerelchuluun, Ariungerel; Hong, Zhengshan; Moritake, Takashi; Zenkoh, Junko; Tsuboi, Koji; Zheng, Yun-Wen; Taniguchi, Hideki

    2013-01-01

    One-third of patients with medulloblastoma die due to recurrence after various treatments including radiotherapy. Although it has been postulated that cancer stem-like cells are radio-resistant and play an important role in tumor recurrence, the 'stemness' of medulloblastoma cells surviving irradiation has not yet been elucidated. Using a medulloblastoma cell line ONS-76, cells that survived gamma irradiation were investigated on their 'stemness' in vitro. From 10 500 cells, 20 radio-resistant clones were selected after gamma ray irradiation (5 Gy x two fractions) using the replica micro-well technique. These 20 resistant clones were screened for CD133 positivity by flow cytometry followed by side population assay, tumor sphere formation assay and clonogenic survival assay. Results revealed CD133 fractions were significantly elevated in three clones, which also exhibited significantly increased levels of tumor sphere formation ability and side population fraction. Clonogenic survival assay demonstrated that their radio-resistance was significantly higher than the parental ONS-76. This may support the hypothesis that a small number of cancer stem-like cells (CSCs) are the main culprits in local recurrence after radiotherapy, and disruption of the resistance mechanism of these CSCs is a critical future issue in improving the outcome of patients with medulloblastoma. (author)

  4. Down-regulation of survivin by oxaliplatin diminishes radioresistance of head and neck squamous carcinoma cells

    International Nuclear Information System (INIS)

    Khan, Zakir; Khan, Noor; Tiwari, Ram P.; Patro, Ishan K.; Prasad, G.B.K.S.; Bisen, Prakash S.

    2010-01-01

    Background: Oxaliplatin is integrated in treatment strategies against a variety of cancers including radiation protocols. Herein, as a new strategy we tested feasibility and rationale of oxaliplatin in combination with radiation to control proliferation of head and neck squamous cell carcinoma (HNSCC) cells and discussed survivin-related signaling and apoptosis induction. Methods: Cytotoxicity and apoptosis induced by radiation and/or oxaliplatin were examined in relation to survivin status using two HNSCC cell lines viz., Cal27 and NT8e, and one normal 293-cell line. Survivin gene knockdown by siRNA was also tested in relevance to oxaliplatin-mediated radiosensitization effects. Results: Survivin plays a critical role in mediating radiation-resistance in part through suppression of apoptosis via a caspase-dependent mechanism. Oxaliplatin treatment significantly decreased expression of survivin in cancer cells within 24-72 h. Apoptotic cells and caspase-3 activity were increased parallely with decrease in cell viability, if irradiated during this sensitive period. The cytotoxicity of oxaliplatin and radiation combination was greater than additive. Survivin gene knockdown experiments have demonstrated the role of survivin in radiosensitization of cancer cells mediated by oxaliplatin. Conclusions: Higher expression of survivin is a critical factor for radioresistance in HNSCC cell lines. Pre-treatment of cancer cells with oxaliplatin significantly increased the radiosensitivity through induction of apoptosis by potently inhibiting survivin.

  5. Novel pattern of post-γ ray de novo DNA synthesis in a radioresistant human strain

    International Nuclear Information System (INIS)

    Mirzayans, R.; Gentner, N.E.; Paterson, M.C.

    1985-01-01

    Enhanced resistance to radiation cytotoxicity in a fibroblast strain from an afflicted member of a Li-Fraumeni syndrome family may be largely ascribable to a change in the pattern of DNA replicative synthesis following γ ray exposure. That is, the extent of the initial radiogenic inhibition of replicative synthesis and the time interval before its subsequent recovery were both found to be greater in radioresistant (RR) compared to normal cells. In addition, the post-recovery replication rates in the RR cells were both higher and longer lasting than those in the control cells. A similar differential pattern was also seen following treatment with 4NQO, another DNA-damaging agent to which this RR strain displays enhanced resistance. Moreover, several conventional DNA repair assays indicated that the RR cells repair radiogenic damage at normal rates. The authors therefore suggest that the increased inhibition and prolonged lag in resumption of replicative synthesis seen in the RR strain upon exposure to certain genotoxic agents may enhance cellular recovery by ''buying additional time'' for processing of potentially lethal lesions

  6. Effect of individual and group housing of mice on the level of radioresistance

    Directory of Open Access Journals (Sweden)

    Dorozhkina O.V.

    2015-12-01

    Full Text Available Aim: to examine the effect of individual and group housing of mice on radioresistance. Material and methods. Effects of individual and group housing of mice on immunity and blood systems were studied on ICR (CD-1 and C57BI6 male mice before and after proton irradiation. Results. Group housing of intact animals resulted in a decline in the number of nucleated cells in the femur bone marrow and thymus mass. The irradiation with proton with energy of 171 MeV at a dose of 1 Gy causes a statistically significant greater reduction of the number of nucleated cells in the femur bone marrow in group-housed mice. A trend toward greater safety of the number of leukocytes in the peripheral blood and higher proliferative activity of bone marrow cells, as well as lower level of aberrant mitoses have been noted in individually-housed mice. Reduction processes in the recovery period of radiation sickness take place at a greater rate in group-housed mice. Conclusion. Group housing of male mice causes increased sensitivity of the blood and immunity systems to the effects of radiation and at the same time accelerates processes of radiation recovery.

  7. Radioresistance of intermediate TCR cells and their localization in the body of mice revealed by irradiation

    International Nuclear Information System (INIS)

    Kimura, Motohiko; Watanabe, Hisami; Ohtsuka, Kazuo; Iiai, Tsuneo; Tsuchida, Masanori; Sato, Shotaro; Abo, Toru

    1993-01-01

    Extrathymic generation of T cells in the liver and in the intestine was recently demonstrated. We investigated herein whether such T cells, especially those in the liver, are present in other organs of mice. This investigation is possible employing our recently introduced method with which even a minor proportion of extrathymic, intermediate T-cell receptor (TCR) cells in organs other than the liver can be identified. Intermediate TCR cells expressed higher levels of IL-2Rβ and lymphocyte function-associated antigen-1 (LFA-1) than bright TCR cells (i.e., T cells of thymic origin) as revealed by two-color staining. Although intermediate TCR cells were present at a small proportion in the spleen and thymus, they predominated in these organs after irradiation (9 Gy) and bone marrow reconstitution, or after low dose irradiation (6 Gy). This was due to that intermediate TCR cells were relatively radioresistant, whereas bright TCR cells were radiosensitive. Microscopic observation and immunochemical staining showed that intermediate TCR cells in the spleen localized in the red pulp and those in the thymus localized in the medulla. These intermediate TCR cells displayed a large light scatter, similar to such cells in the liver. The present results suggest that intermediate TCR cells may proliferate at multiple sites in the body. (author)

  8. Alterations in transcription factor binding in radioresistant human melanoma cells after ionizing radiation

    International Nuclear Information System (INIS)

    Sahijdak, W.M.; Yang, Chin-Rang; Zuckerman, J.S.; Meyers, M.; Boothman, D.A.

    1994-01-01

    We analyzed alterations in transcription factor binding to specific, known promoter DNA consensus sequences between irradiated and unirradiated radioresistant human melanoma (U1-Mel) cells. The goal of this study was to begin to investigate which transcription factors and DNA-binding sites are responsible for the induction of specific transcripts and proteins after ionizing radiation. Transcription factor binding was observed using DNA band-shift assays and oligonucleotide competition analyses. Confluence-arrested U1-Mel cells were irradiated (4.5 Gy) and harvested at 4 h. Double-stranded oligonucleotides containing known DNA-binding consensus sites for specific transcription factors were used. Increased DNA binding activity after ionizing radiation was noted with oligonucleotides containing the CREB, NF-kB and Sp1 consensus sites. No changes in protein binding to AP-1, AP-2, AP-3, or CTF/NF1, GRE or Oct-1 consensus sequences were noted. X-ray activation of select transcription factors, which bind certain consensus sites in promoters, may cause specific induction or repression of gene transcription. 22 refs., 2 figs

  9. Bimodal cell death induced by high radiation doses in the radioresistant sf9 insect cell line

    International Nuclear Information System (INIS)

    Chandna, S.

    2003-01-01

    Full text: This study was conducted to investigate the mode(s) of cell death induced by high radiation doses in the highly radioresistant Sf9 insect ovarian cell line. Methods: Cells were exposed to γ-radiation doses 200Gy and 500Gy, harvested at various time intervals (6h-72h) following irradiation, and subjected to cell morphology assay, DNA agarose gel electrophoresis, single cell gel electrophoresis (SCGE; comet assay) and Annexin-V labeling for the detection of membrane phosphatidylserine externalization. Cell morphology was assessed in cells entrapped and fixed in agarose gel directly from the cell suspension, thus preventing the possible loss of fragments/ apoptotic bodies. Surviving fraction of Sf9 cells was 0.01 at 200Gy and 98%) undergoing extensive DNA fragmentation at 500Gy, whereas the frequency of cells with DNA fragmentation was considerably less (∼12%) at 200Gy. Conclusions: While the mode of cell death at 200Gy seems to be different from typical apoptosis, a dose of 500Gy induced bimodal cell death, with typical apoptotic as well as the atypical cell death observed at 200Gy

  10. 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

  11. Possible association between stem-like hallmark and radioresistance in human cervical carcinoma cells.

    Science.gov (United States)

    Kumazawa, Shoko; Kajiyama, Hiroaki; Umezu, Tomokazu; Mizuno, Mika; Suzuki, Shiro; Yamamoto, Eiko; Mitsui, Hiroko; Sekiya, Ryuichiro; Shibata, Kiyosumi; Kikkawa, Fumitaka

    2014-05-01

    We aimed to investigate the possibility of an association between a stem-like hallmark and radiotherapeutic sensitivity in human cervical carcinoma cells. Side-population (SP) cells and non-SP (NSP) cells in HeLa cells were isolated using flow cytometry and Hoechst 33342 efflux. We performed Western blot analysis to evaluate the expression of stem cell markers (CXCR4, Oct3/4, CD133, and SOX2) and apoptosis markers after irradiation. In addition, SP and NSP cells were injected into nude mice and we assessed subcutaneous tumor formation. To examine tolerance of irradiation, colony formation and apoptosis change were confirmed in the SP and NSP cells. SP cells showed a higher expression of CXCR4, Oct3/4, CD133, and SOX2 than NSP cells. The colony size of SP cells cultured on non-coated dishes was larger than that of NSP cells, and NSP cells were easily induced to undergo apoptosis. SP cells tended to form spheroids and showed a higher level of tumorigenicity compared with NSP cells. In addition, nude mice inoculated with SP cells showed greater tumor growth compared with NSP cells. SP cells showed a higher tumorigenicity and lower apoptotic potential, leading to enhanced radiotolerance. Tumor SP cells showed higher-level stem-cell-like characters and radioresistance than NSP cells. SP cells may be useful for new therapeutic approaches for radiation-resistant cervical cancer. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

  12. Critical analysis of salvage radical prostatectomy in the management of radioresistant prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Seabra, Daniel; Faria, Eliney; Dauster, Breno; Rodrigues, Gunther; Fava, Gilberto [Pio XII Foundation, Barretos, SP (Brazil). Section of Urology], e-mail: daniel.seabra@terra.com.br

    2009-01-15

    Purpose: To critically evaluate salvage radical prostatectomy (SRP) in the treatment of patients with recurrent prostate cancer (PCa). Materials and Methods: From January 2005 to June 2007, we assessed patients with recurrent localized PCa. Recurrence was suspected when there were three or more successive increases in prostate specific antigen (PSA) after nadir. After the routine imagery examinations, and once localized PCa was confirmed, patients were offered SRP. Following surgery, we evaluated bleeding, rectal injury, urinary incontinence or obstruction and impotence. PSA values were measured at 1, 3, 6, months and thereafter twice a year. Results: Forty-two patients underwent SRP. The average age was 61 years. Following radiotherapy , the mean PSA nadir was 1.5 ng/mL (0.57-5.5). The mean prostate specific antigen doubling time (PSA-DT) was 14 months (6-20). Prior to SRP, the mean PSA was 5.7 ng/mL (2.9-18). The pathologic staging was pT2a: 13%; pT2b: 34%; pT2c: 27%; pT3a: 13%; and pT3b: 13%. Bleeding > 600 mL occurred in 14% of the cases; urethral stenosis in 50%; and urinary incontinence (two or more pads/day) in 72%. The mean follow-up post-SRP ranged from 6 to 30 months. The PSA level rose in 9, of which 6 had PSA-DT < 10 months. Conclusions: SRP is a feasible method in the management of localized radioresistant PCa. PSA-DT has shown to be important for the selection and SRP should not be performed if PSA-DT > 10 months. Due to its increased morbidity, SRP should be only offered to the patients who are more concerned about survival rather than quality of life. (author)

  13. Effects of radiation type and delivery mode on a radioresistant eukaryote Cryptococcus neoformans

    International Nuclear Information System (INIS)

    Shuryak, Igor; Bryan, Ruth A.; Broitman, Jack; Marino, Stephen A.; Morgenstern, Alfred; Apostolidis, Christos; Dadachova, Ekaterina

    2015-01-01

    Introduction: Most research on radioresistant fungi, particularly on human pathogens such as Cryptococcus neoformans, involves sparsely-ionizing radiation. Consequently, fungal responses to densely-ionizing radiation, which can be harnessed to treat life-threatening fungal infections, remain incompletely understood. Methods: We addressed this issue by quantifying and comparing the effects of densely-ionizing α-particles (delivered either by external beam or by 213 Bi-labeled monoclonal antibodies), and sparsely-ionizing 137 Cs γ-rays, on Cryptococus neoformans. Results: The best-fit linear-quadratic parameters for clonogenic survival were the following: α = 0.24 × 10 −2 Gy −1 for γ-rays and 1.07 × 10 −2 Gy −1 for external-beam α-particles, and β = 1.44 × 10 −5 Gy −2 for both radiation types. Fungal cell killing by radiolabeled antibodies was consistent with predictions based on the α-particle dose to the cell nucleus and the linear-quadratic parameters for external-beam α-particles. The estimated RBE (for α-particles vs. γ-rays) at low doses was 4.47 for the initial portion of the α-particle track, and 7.66 for the Bragg peak. Non-radiological antibody effects accounted for up to 23% of cell death. Conclusions: These results quantify the degree of C. neoformans resistance to densely-ionizing radiations, and show how this resistance can be overcome with fungus-specific radiolabeled antibodies

  14. Vive la radiorésistance!: converging research in radiobiology and biogerontology to enhance human radioresistance for deep space exploration and colonization

    Science.gov (United States)

    Cortese, Franco; Klokov, Dmitry; Osipov, Andreyan; Stefaniak, Jakub; Moskalev, Alexey; Schastnaya, Jane; Cantor, Charles; Aliper, Alexander; Mamoshina, Polina; Ushakov, Igor; Sapetsky, Alex; Vanhaelen, Quentin; Alchinova, Irina; Karganov, Mikhail; Kovalchuk, Olga; Wilkins, Ruth; Shtemberg, Andrey; Moreels, Marjan; Baatout, Sarah; Izumchenko, Evgeny; de Magalhães, João Pedro; Artemov, Artem V.; Costes, Sylvain V.; Beheshti, Afshin; Mao, Xiao Wen; Pecaut, Michael J.; Kaminskiy, Dmitry; Ozerov, Ivan V.; Scheibye-Knudsen, Morten; Zhavoronkov, Alex

    2018-01-01

    While many efforts have been made to pave the way toward human space colonization, little consideration has been given to the methods of protecting spacefarers against harsh cosmic and local radioactive environments and the high costs associated with protection from the deleterious physiological effects of exposure to high-Linear energy transfer (high-LET) radiation. Herein, we lay the foundations of a roadmap toward enhancing human radioresistance for the purposes of deep space colonization and exploration. We outline future research directions toward the goal of enhancing human radioresistance, including upregulation of endogenous repair and radioprotective mechanisms, possible leeways into gene therapy in order to enhance radioresistance via the translation of exogenous and engineered DNA repair and radioprotective mechanisms, the substitution of organic molecules with fortified isoforms, and methods of slowing metabolic activity while preserving cognitive function. We conclude by presenting the known associations between radioresistance and longevity, and articulating the position that enhancing human radioresistance is likely to extend the healthspan of human spacefarers as well. PMID:29581875

  15. Proteomic profiling identifies PTK2/FAK as a driver of radioresistance in HPV-negative head and neck cancer

    Science.gov (United States)

    Skinner, Heath D.; Giri, Uma; Yang, Liang P.; Woo, Sang Hyeok; Story, Michael; Pickering, Curtis; Byers, Lauren; Williams, Michelle; El Naggar, Adel; Wang, Jing; Diao, Lixia; Shen, Li; Fan, You Hong; Molkentine, David; Beadle, Beth; Meyn, Raymond; Myers, Jeffrey; Heymach, John

    2016-01-01

    Purpose Head and neck squamous cell carcinoma (HNSCC) is commonly treated with radiotherapy, and local failure after treatment remains the major cause of disease-related mortality. To date human papillomavirus (HPV) is the only known clinically validated, targetable biomarkers of response to radiation in HNSCC. Experimental Design We performed proteomic and transcriptomic analysis of targetable biomarkers of radioresistance in HPV-negative HNSCC cell lines in vitro, and tested whether pharmacologic blockade of candidate biomarkers sensitized cells to radiotherapy. Candidate biomarkers were then investigated in several independent cohorts of patients with HNSCC. Results Increased expression of several targets was associated with radioresistance, including FGFR, ERK1, EGFR, and focal adhesion kinase (FAK), also known as PTK2. Chemical inhibition of PTK2/FAK, but not FGFR, led to significant radiosensitization with increased G2/M arrest and potentiated DNA damage. PTK2/FAK overexpression was associated with gene amplification in HPV-negative HNSCC cell lines and clinical tumors. In two independent cohorts of patients with locally advanced HPV-negative HNSCC, PTK2/FAK amplification was highly associated with poorer disease-free survival (DFS) (P=0.012 and P=0.034). PTK2/FAK mRNA expression was also associated with worse DFS (P=0.03). Moreover, both PTK2/FAK mRNA (P=0.021) and copy number (P=0.063) were associated with DFS in the Head and Neck Cancer subgroup of The Cancer Genome Atlas. Conclusion Proteomic analysis identified PTK2/FAK overexpression is a biomarker of radioresistance in locally advanced HNSCC, and PTK2/FAK inhibition radiosensitized HNSCC cells. Combinations of PTK2/FAK inhibition with radiotherapy merit further evaluation as a therapeutic strategy for improving local control in HPV-negative HNSCC. PMID:27036135

  16. CD133+ cells contribute to radioresistance via altered regulation of DNA repair genes in human lung cancer cells

    International Nuclear Information System (INIS)

    Desai, Amar; Webb, Bryan; Gerson, Stanton L.

    2014-01-01

    Background: Radioresistance in human tumors has been linked in part to a subset of cells termed cancer stem cells (CSCs). The prominin 1 (CD133) cell surface protein is proposed to be a marker enriching for CSCs. We explore the importance of DNA repair in contributing to radioresistance in CD133+ lung cancer cells. Materials and methods: A549 and H1299 lung cancer cell lines were used. Sorted CD133+ cells were exposed to either single 4 Gy or 8 Gy doses and clonogenic survival measured. ϒ-H2AX immunofluorescence and quantitative real time PCR was performed on sorted CD133+ cells both in the absence of IR and after two single 4 Gy doses. Lentiviral shRNA was used to silence repair genes. Results: A549 but not H1299 cells expand their CD133+ population after single 4 Gy exposure, and isolated A549 CD133+ cells demonstrate IR resistance. This resistance corresponded with enhanced repair of DNA double strand breaks (DSBs) and upregulated expression of DSB repair genes in A549 cells. Prior IR exposure of two single 4 Gy doses resulted in acquired DNA repair upregulation and improved repair proficiency in both A549 and H1299. Finally Exo1 and Rad51 silencing in A549 cells abrogated the CD133+ IR expansion phenotype and induced IR sensitivity in sorted CD133+ cells. Conclusions: CD133 identifies a population of cells within specific tumor types containing altered expression of DNA repair genes that are inducible upon exposure to chemotherapy. This altered gene expression contributes to enhanced DSB resolution and the radioresistance phenotype of these cells. We also identify DNA repair genes which may serve as promising therapeutic targets to confer radiosensitivity to CSCs

  17. The acquired radioresistance in HeLa cells under conditions mimicking hypoxia was attenuated by a decreased expression of HIF subunit genes induced by RNA interference

    International Nuclear Information System (INIS)

    Doi, Nobutaka; Ogawa, Ryohei; Cui, Zheng-Guo; Morii, Akihiro; Watanabe, Akihiko; Kanayama, Shinji; Yoneda, Yuko; Kondo, Takashi

    2015-01-01

    The cancer cells residing in the hypoxic layer are resistant to radiation and these are ones responsible for cancer recurrence after radiation therapy. One of the reasons why hypoxic cancer cells acquire radioresistance may be attributable to changes in the gene expression profile by the activation of hypoxia inducible factors (HIFs). However, the details underlying this process remain unknown. In this study, we investigated the effects of knockdown of HIF subunit genes to elucidate how HIF subunit genes may be involved in the radioresistance acquired by HeLa cells following exposure to a hypoxia mimic. Interestingly, HIF-1α and HIF-2α seemed mutually complementary for each other when either of them was suppressed. We thus suppressed the expression of both genes simultaneously. To do this, we developed a short hairpin RNA (shRNA) targeting a high homology region between HIF-1α and HIF-2α. It was shown that the expression of the shRNA effectively suppressed the acquisition of radioresistance following the hypoxia mimic. Moreover, it was confirmed that suppression of both subunits resulted in the downregulation of stem cell markers and the suppression of spheroid formation during the hypoxia mimicking-conditions. This shRNA-mediated knockdown method targeting a common region shared by a family of genes may offer a new candidate cancer treatment. - Highlights: • Incubation with CoCl 2 confers radioresistance to HeLa cells. • Both HIF-1α and HIF-2α are involved in the acquisition of radioresistance. • An shRNA to a homology region of HIF-1α and HIF-2α suppressed the radioresistance. • The shRNA decreased cells with stem cell markers and a stem cell phenotype

  18. The acquired radioresistance in HeLa cells under conditions mimicking hypoxia was attenuated by a decreased expression of HIF subunit genes induced by RNA interference

    Energy Technology Data Exchange (ETDEWEB)

    Doi, Nobutaka [Department of Radiological Sciences, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194 (Japan); New Products Research & Development, Gene Engineering Division, NIPPON GENE Co., Ltd. (Japan); Ogawa, Ryohei, E-mail: ogawa@med.u-toyama.ac.jp [Department of Radiological Sciences, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194 (Japan); Cui, Zheng-Guo [Department of Public Health, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama (Japan); Morii, Akihiro; Watanabe, Akihiko [Department of Urology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama (Japan); Kanayama, Shinji; Yoneda, Yuko [New Products Research & Development, Gene Engineering Division, NIPPON GENE Co., Ltd. (Japan); Kondo, Takashi [Department of Radiological Sciences, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194 (Japan)

    2015-05-01

    The cancer cells residing in the hypoxic layer are resistant to radiation and these are ones responsible for cancer recurrence after radiation therapy. One of the reasons why hypoxic cancer cells acquire radioresistance may be attributable to changes in the gene expression profile by the activation of hypoxia inducible factors (HIFs). However, the details underlying this process remain unknown. In this study, we investigated the effects of knockdown of HIF subunit genes to elucidate how HIF subunit genes may be involved in the radioresistance acquired by HeLa cells following exposure to a hypoxia mimic. Interestingly, HIF-1α and HIF-2α seemed mutually complementary for each other when either of them was suppressed. We thus suppressed the expression of both genes simultaneously. To do this, we developed a short hairpin RNA (shRNA) targeting a high homology region between HIF-1α and HIF-2α. It was shown that the expression of the shRNA effectively suppressed the acquisition of radioresistance following the hypoxia mimic. Moreover, it was confirmed that suppression of both subunits resulted in the downregulation of stem cell markers and the suppression of spheroid formation during the hypoxia mimicking-conditions. This shRNA-mediated knockdown method targeting a common region shared by a family of genes may offer a new candidate cancer treatment. - Highlights: • Incubation with CoCl{sub 2} confers radioresistance to HeLa cells. • Both HIF-1α and HIF-2α are involved in the acquisition of radioresistance. • An shRNA to a homology region of HIF-1α and HIF-2α suppressed the radioresistance. • The shRNA decreased cells with stem cell markers and a stem cell phenotype.

  19. Heavy metals-bioremediation by highly radioresistant Deinococcus radiodurans biofilm prospective use in nuclear reactor decontamination

    International Nuclear Information System (INIS)

    Shukla, Sudhir K.; Subba Rao, T.

    2015-01-01

    Over the past few decades, rapid growth of chemical industries have enhanced the heavy metal contamination in water, thereby raising environmental concerns. In the nuclear power industry, decontamination procedure also generates radioactive heavy metal containing wastes. Radio-resistant Deinococcus radiodurans R1 is reported to be a potential candidate for the treatment of low active waste material. To use any bacterium for bioremediation purpose, knowledge about its biofilm production characteristics is a prerequisite. This is because biofilm-mediated bioremediation processes are more efficient as compared to processes mediated by their planktonic counterparts. However, so far there are no reports on the biofilm producing capability of D. radiodurans. We observed that tagging of D. radiodurans by a plasmid harbouring gfp and kan R conferred significant biofilm producing property to the bacterium. Chemical analysis of biofilm matrix components produced by D. radiodurans showed that the matrix consists primarily of proteins and carbohydrates with small amount of extracellular DNA (eDNA). Further, we studied the effect of Ca 2+ on D. radiodurans biofilm formation and it was observed that D. radiodurans biofilm formation was enhanced at higher concentrations of Ca 2+ . We investigated the capability of D. radiodurans biofilm to remove the heavy metals Co and Ni from synthetic waste streams. Results showed that Ca 2+ enhanced the bioremediation of both heavy metals (Co, Ni) by D. radiodurans biofilms in a highly significant manner. In the presence of 50 mM Ca 2+ 35% Co removal and 25% Ni removal was observed, when compared to biofilm grown in the absence of Ca 2+ , which showed mere 7% Co and 3% Ni removal, respectively. The results showed that the presence of Ca 2+ significantly enhanced exopolysaccharide and eDNA (both negatively charged) production in the biofilm matrix. This indicated adsorption could be the major mechanism behind enhanced biofilm mediated removal

  20. Identification of CD133-positive radioresistant cells in atypical teratoid/rhabdoid tumor.

    Directory of Open Access Journals (Sweden)

    Shih-Hwa Chiou

    2008-05-01

    Full Text Available Atypical teratoid/rhabdoid tumor (AT/RT is an extremely malignant neoplasm in the central nervous system (CNS which occurs in infancy and childhood. Recent studies suggested that CD133 could be considered a marker for brain cancer stem-like cells (CSCs. However, the role of CD133 in AT/RT has never been investigated. Herein we report the isolation of CD133-positive cells (CD133(+, found to have the potential to differentiate into three germ layer tissues, from tissues of nine AT/RT patients. The migration/invasion/malignancy and radioresistant capabilities of CD133(+ were significantly augmented when compared to CD133(-. The clinical data showed that the amount of CD133(+ in AT/RTs correlated positively with the degree of resistance to radiation therapy. Using cDNA microarray analysis, the genotoxic-response profiles of CD133(+ and CD133(- irradiated with 10 Gy ionizing radiation (IR were analyzed 0.5, 2, 6, 12 and 24 h post-IR. We then validated these microarray data and showed increased phosphorylation after IR of p-ATM, p-RAD17, and p-CHX2 as well as increased expression of BCL-2 protein in CD133(+ compared to CD133(-. Furthermore, we found that CD133(+ can effectively resist IR with cisplatin- and/or TRAIL-induced apoptosis. Immunohistochemical analysis confirmed the up-regulated expression of p-ATM and BCL-2 proteins in IR-treated CD133(+ xenotransgrafts in SCID mice but not in IR-treated CD133(-. Importantly, the effect of IR in CD133(+ transplanted mice can be significantly improved by a combination of BCL-2 siRNA with debromohymenialdisine, an inhibitor of checkpoint kinases. In sum, this is the first report indicating that CD133(+ AT/RT cells demonstrate the characteristics of CSCs. The IR-resistant and anti-apoptotic properties in CD133(+ may reflect the clinical refractory malignancy of AT/RTs and thus the activated p-ATM pathway and BCL-2 expression in CD133(+ could be possible targets to improve future treatment of deadly diseases

  1. Melatonin suppresses thyroid cancer growth and overcomes radioresistance via inhibition of p65 phosphorylation and induction of ROS

    Directory of Open Access Journals (Sweden)

    Zhen-Wei Zou

    2018-06-01

    Full Text Available Thyroid cancer is the most common endocrine carcinoma with increasing incidence worldwide and anaplastic subtypes are frequently associated with cancer related death. Radioresistance of thyroid cancer often leads to therapy failure and cancer-related death. In this study, we found that melatonin showed potent suppressive roles on NF-κB signaling via inhibition of p65 phosphorylation and generated redox stress in thyroid cancer including the anaplastic subtypes. Our data showed that melatonin significantly decreased cell viability, suppressed cell migration and induced apoptosis in thyroid cancer cell lines in vitro and impaired tumor growth in the subcutaneous mouse model in vivo. By contrast, irradiation of thyroid cancer cells resulted in elevated level of phosphorylated p65, which could be reversed by cotreatment with melatonin. Consequently, melatonin synergized with irradiation to induce cytotoxicity to thyroid cancer, especially in the undifferentiated subgroups. Taken together, our results suggest that melatonin may exert anti-tumor activities against thyroid carcinoma by inhibition of p65 phosphorylation and induction of reactive oxygen species. Radio-sensitization by melatonin may have clinical benefits in thyroid cancer. Keywords: Melatonin, Thyroid cancer, Radioresistance, p65, Reactive oxygen species

  2. The role of oxidative stress in EBV lytic reactivation, radioresistance and the potential preventive and therapeutic implications.

    Science.gov (United States)

    Hu, Jianmin; Li, Hongde; Luo, Xiangjian; Li, Yueshuo; Bode, Ann; Cao, Ya

    2017-11-01

    Epstein-Barr virus (EBV) is an important cancer causing virus. Cancer associated with EBV account for approximately 1.5% of all cancers, and represent 1.8% of all cancer deaths worldwide. EBV reactivation plays an important role in the development of EBV-related diseases and is closely related with patients' survival and clinical stages of EBV-related cancers. The therapy regarding to EBV-related cancers is very urgent, especially in endemic areas. Generating oxidative stress is a critical mechanism by which host cells defend against infection by virus. In addition, ROS-mediated oxidative stress plays a significant but paradoxical role acting as a "double-edged sword" to regulate cellular response to radiation, which is the main therapy strategy for EBV-related cancers, especially nasopharyngeal carcinoma. Therefore, in this review we primarily discuss the possible interplay among the oxidative stress, EBV lytic reactivation and radioresistance. Understanding the role of oxidative stress in EBV lytic reactivation and radioresistance will assist in the development of effective strategies for prevention and treatment of EBV-related cancers. © 2017 UICC.

  3. Intrathymic radioresistant stem cells follow an IL-2/IL-2R pathway during thymic regeneration after sublethal irradiation

    International Nuclear Information System (INIS)

    Zuniga-Pfluecker, J.C.K.; Kruisbeek, A.M.

    1990-01-01

    Sublethally irradiated mice undergo thymic regeneration which follows a phenotypic pattern of events similar to that observed during normal fetal development. Thymic regeneration after irradiation is the product of a limited pool of intrathymic radioresistant stem cells undergoing simultaneous differentiation. We show that in this model of T cell development, thymic regeneration follows a pathway in which the IL-2R is transiently expressed on CD4-/CD8- cells. IL-2R expression occurred during the exponential growth period of thymic regeneration, and IL-2R blocking prevented this explosive growth. Flow cytometry analysis revealed that the IL-2R blockade affected primarily the development of the immature CD3-/CD4-/CD8- (triple negative) cells and their ability to generate CD3+/CD4+/CD8+ or CD3+/CD4+/CD8- and CD3+/CD4-/CD8+ thymocytes. Thus, our findings demonstrate that blocking of the IL-2R resulted in an arrest in proliferation and differentiation by intrathymic radioresistant stem cells, indicating that the IL-2/IL-2R pathway is necessary for the expansion of immature triple negative T cells

  4. A preliminary investigation into the extent of increased radioresistance or hyper-radiosensitivity in cells of hamster cell lines known to be deficient in DNA repair

    International Nuclear Information System (INIS)

    Skov, K.; Marples, B.; Matthews, J.B.; Zhou, H.; Joiner, M.C.

    1994-01-01

    The response to low doses of X rays was assessed in cells of three hamster cell lines which are defective in DNA repair and was compared with their parental lines. Cells of the V79-derived double-strand break repair-deficient line XR-V15B showed no radioresistance in the 0.5-Gy range compared with the V79B wild type, but instead showed an exponential response. Cells of the single-strand break repair-deficient line EM9 showed hyper-radiosensitivity and exhibited increased radioresistance. Most interestingly, cells of the UV-20 cell line appeared to respond exponentially, as a continuation of the hyper-radiosensitive portion of the curve, with no evidence of increased radioresistance. This line is defective in an incision step of excision repair and is sensitive to crosslinking agents. Further studies are warranted to address the possible role of single- and double-strand break repair and excision repair in hyper-radiosensitivity and increased radioresistance. 24 refs., 4 figs

  5. Lambda bacteriophage gene products and x-ray sensitivity of Escherichia coli: comparison of red-dependent and gam-dependent radioresistance

    International Nuclear Information System (INIS)

    Trgovcevic, Z.; Rupp, W.D.

    1975-01-01

    When gene products of lambda bacteriophage are introduced into a cell by transient induction of a lysogen, increased resistance of the cells to x rays results. This phenomenon has been called phage-induced radioresistance. Genetic studies show at least two classes of induced radioresistance. The first type depends on the products of the lambda red genes and is observed in bacteria that are mutated in the recB gene. It is thought that the lambda red products compensate for the missing RecBC nuclease in the repair of x-ray damage. An optimal effect is obtained even when the lambda red products are supplied 1 h after irradiation. The lesions that are affected by the red-dependent process are probably not deoxyribonucleic acid strand breaks because the extent of deoxyribonucleic acid strand rejoining is not altered by the red products. The second type of phage-induced radioresistance requires the gam product of lambda and is observed in wild-type and polA strains. The lambda gam + gene product must be present immediately after irradiation to exert its full effect. In its presence, DNA breakdown is decreased, and a greater fraction of DNA is converted back to high molecular weight. Strains carrying lex, recA, or certain other combinations of mutations do not show any detectable phage-induced radioresistance. (U.S.)

  6. The influence of nalidixic acid and nicotinamide of the radiation-induced cytogenetic injury to hexaploid wheat varities contrast by radioresistance

    International Nuclear Information System (INIS)

    Selezneva, E.M.; Sarapul'tsev, B.I.

    1990-01-01

    Nalidixic acid modifies the cytogenetic injury when only applied to seeds of a radiosensitive variety, Moskovskaya 35. The radioprotective effect of nicotinamide on both radiosensitive and radioresistant hexaploid wheat varities is observed being dependent on the extent which the genetic apparatus is impaired

  7. Role of insulin-like growth factor-I receptor (IGF-IR) in survival kinetics and radioresistance of mouse embryo fibroblasts in a hypoxic environment

    International Nuclear Information System (INIS)

    Okochi, Kiyoshi

    2002-01-01

    The role of insulin-like growth factor-I receptor (IGF-IR) in survival kinetics and radioresistance of fibroblasts in a severely hypoxic environment (partial oxygen pressure of less than 3 mmHg) was analyzed, in both low and high cell-density conditions. Mouse embryonic fibroblasts R(-), with a targeted disruption of the IGF-IR gene, and R(+) cells, derived from R(-) cells stably transfected with a plasmid containing a human IGF-IR cDNA, were used for this purpose. Survival time in hypoxia was longer in R(+) cells than R(-) cells, which correlated with highly elevated expression of caspase 3-like activity in R(-) cells, but not with HIF-Iα expression. Under euoxia, R(+) cells were more radioresistant, by a factor of 1.9, than R(-) cells. Under hypoxia, R(+) cells became more radioresistant, with an oxygen-enhancement ratio (OER) of 2.7, than R(-) cells, with an OER of 1.5, in a low cell density. However, unexpected hyper-radiosensitivity in hypoxia was observed for both R(+) and R(-) cells in a high cell density, which further increased with incubation time in hypoxia following X-irradiation. The hyper-radiosensitivity was more pronounced for R(-) cells. The result thus implies that IGF-IR may be an important target molecule for radioresistant tumors in radiotherapy. (author)

  8. The role of natural radioresistance and ecological specialization of a specie in radio adaptation (as exemplified by natural rodent populations)

    Energy Technology Data Exchange (ETDEWEB)

    Grigorkina, E.; Olenev, G. [Institute of Plant and Animal Ecology, Ural Branch RAS, Ekaterinburg, (Russian Federation)

    2004-07-01

    The problem of mammal radio-adaptation is closely connected with problems of micro-evolution and prediction of the fate of irradiated populations. This report gives new materials on radio-adaptation of small mammals inhabiting the East Ural Radioactive Trace (EURT) which has been formed after the Kyshtym accident in 1957 year. The EURT zone is a unique area for studying long-term consequences of chronic low-dose irradiation of small mammal populations many generations being born after the accident. The role of natural radioresistance, ecological specialization and biological characteristics of a specie in the development of radio-adaptation are discussed. The objects of investigation were rodents: 1) Ellobius talpinus is a peculiar specialized specie with low ability to migrate, burrowing underground way of life and lifespan up to 6 years; 2) Sylvaemus uralensis, Apodemus agrarius, Clethrionomys rutilus widespread aboveground species, very active migrators with a 1.5 year lifespan. Significant differences were found among species in natural radioresistance to acute gamma-irradiation. LD{sub 50/30} is 5.0{+-}0.7 Gy for the Ellobius talpinus, 7.0{+-}0.4 Gy for the Sylvaemus uralensis, 10.0{+-}0.2 Gy for the Apodemus agrarius, 12.8{+-}0.2 Gy for the Clethrionomys rutilus. Despite the high radiosensitivity the Ellobius talpinus was more tolerant to chronic irradiation (over 45 years inhabiting the EURT, soil pollution by {sup 90}Sr was 950-1050 Ci/km{sup 2} - 35-39 MBq/m{sup 2}) in a complex of morpho-physiological, haematological and immunological parameters, than other species with active migration activity (the initial pollution of soil by {sup 90}Sr was 400-540 Ci/km{sup 2} - 15-20 MBq/m{sup 2}). This phenomenon is explained by radio-adaptation which developed in the Ellobius talpinus due to isolation of their settlement in the periphery of the area in conditions of radio-contamination. Various radioresistance to acute and chronic irradiation, disproportion of

  9. Cancer-initiating cells derived from established cervical cell lines exhibit stem-cell markers and increased radioresistance

    International Nuclear Information System (INIS)

    López, Jacqueline; Poitevin, Adela; Mendoza-Martínez, Veverly; Pérez-Plasencia, Carlos; García-Carrancá, Alejandro

    2012-01-01

    Cancer-initiating cells (CICs) are proposed to be responsible for the generation of metastasis and resistance to therapy. Accumulating evidences indicates CICs are found among different human cancers and cell lines derived from them. Few studies address the characteristics of CICs in cervical cancer. We identify biological features of CICs from four of the best-know human cell lines from uterine cervix tumors. (HeLa, SiHa, Ca Ski, C-4 I). Cells were cultured as spheres under stem-cell conditions. Flow cytometry was used to detect expression of CD34, CD49f and CD133 antigens and Hoechst 33342 staining to identify side population (SP). Magnetic and fluorescence-activated cell sorting was applied to enrich and purify populations used to evaluate tumorigenicity in nude mice. cDNA microarray analysis and in vitro radioresistance assay were carried out under standard conditions. CICs, enriched as spheroids, were capable to generate reproducible tumor phenotypes in nu-nu mice and serial propagation. Injection of 1 × 10 3 dissociated spheroid cells induced tumors in the majority of animals, whereas injection of 1 × 10 5 monolayer cells remained nontumorigenic. Sphere-derived CICs expressed CD49f surface marker. Gene profiling analysis of HeLa and SiHa spheroid cells showed up-regulation of CICs markers characteristic of the female reproductive system. Importantly, epithelial to mesenchymal (EMT) transition-associated markers were found highly expressed in spheroid cells. More importantly, gene expression analysis indicated that genes required for radioresistance were also up-regulated, including components of the double-strand break (DSB) DNA repair machinery and the metabolism of reactive oxygen species (ROS). Dose-dependent radiation assay indicated indeed that CICs-enriched populations exhibit an increased resistance to ionizing radiation (IR). We characterized a self-renewing subpopulation of CICs found among four well known human cancer-derived cell lines (HeLa, Si

  10. MiR-20a Induces Cell Radioresistance by Activating the PTEN/PI3K/Akt Signaling Pathway in Hepatocellular Carcinoma

    International Nuclear Information System (INIS)

    Zhang, Yuqin; Zheng, Lin; Ding, Yi; Li, Qi; Wang, Rong; Liu, Tongxin; Sun, Quanquan; Yang, Hua; Peng, Shunli; Wang, Wei; Chen, Longhua

    2015-01-01

    Purpose: To investigate the role of miR-20a in hepatocellular carcinoma (HCC) cell radioresistance, which may reveal potential strategies to improve treatment. Methods and Materials: The expression of miR-20a and PTEN were detected in HCC cell lines and paired primary tissues by quantitative real-time polymerase chain reaction. Cell radiation combined with colony formation assays was administrated to discover the effect of miR-20a on radiosensitivity. Bioinformatics prediction and luciferase assay were used to identify the target of miR-20a. The phosphatidylinositol 3-kinase inhibitor LY294002 was used to inhibit phosphorylation of Akt, to verify whether miR-20a affects HCC cell radioresistance through activating the PTEN/PI3K/Akt pathway. Results: MiR-20a levels were increased in HCC cell lines and tissues, whereas PTEN was inversely correlated with it. Overexpression of miR-20a in Bel-7402 and SMMC-7721 cells enhances their resistance to the effect of ionizing radiation, and the inhibition of miR-20a in HCCLM3 and QGY-7701 cells sensitizes them to it. PTEN was identified as a direct functional target of miR-20a for the induction of radioresistance. Overexpression of miR-20a activated the PTEN/PI3K/Akt signaling pathway. Additionally, the kinase inhibitor LY294002 could reverse the effect of miR-20a–induced radioresistance. Conclusion: MiR-20a induces HCC cell radioresistance by activating the PTEN/PI3K/Akt pathway, which suggests that miR-20a/PTEN/PI3K/Akt might represent a target of investigation for developing effective therapeutic strategies against HCC

  11. γ-Glutamylcysteine synthetase (γ-GCS) as a target for overcoming chemo- and radio-resistance of human hepatocellular carcinoma cells.

    Science.gov (United States)

    Lin, Li-Ching; Chen, Chi-Fen; Ho, Chun-Te; Liu, Jun-Jen; Liu, Tsan-Zon; Chern, Chi-Liang

    2018-04-01

    This study uncovered that the genetically endowed intracellular glutathione contents (iGSH) regulated by the catalytic subunit of γ‑glutamylcysteine synthetase heavy chain (γ‑GCSh) as a prime target for overcoming both the inherited and stimuli-activated chemo- and radio-resistance of hepatocellular carcinoma (HCC) cells. Reactive oxygen species (ROS) production and mitochondrial membrane potential (Δψm) were determined by the probe-based flow cytometry. The TUNEL assay was used as an index of radio-sensitivity and the MTT assay was used as an index of chemo-sensitivity against various anti-cancer agents. iGSH and γ‑GCSh activity were measured by HPLC methods. γ‑GCSh-overexpressing GCS30 cell line was established by tetracycline-controlled Tet-OFF gene expression system in SK-Hep-1 cells. The relative radio-sensitivities of a panel of five HCC cells were found to be correlated negatively with both the contents of iGSH and their corresponding γ‑GCSh activities with an order of abundance being Hep G2 > Hep 3B > J5 > Mahlavu > SK-Hep-1, respectively. Similarly, the cytotoxicity response patterns of these HCC cells against arsenic trioxide (ATO), a ROS-producing anti-cancer drug, were exactly identical to the order of ranking instigated by the radiotherapy (RT) treatment. Next, γ‑GCSh-overexpressing GCS30 cells were found to possess excellent ability to profoundly mitigate both the drop of Δψm and apoptotic TUNEL-positive cell population engendered by ATO, cisplatin, doxorubicin, and RT treatments. Our data unequivocally demonstrate that γ‑GCSh may represent a prime target for overcoming anti-cancer drugs and RT resistance for HCC cells. Copyright © 2018 Elsevier Inc. All rights reserved.

  12. Upregulation of Long Noncoding RNA Small Nucleolar RNA Host Gene 18 Promotes Radioresistance of Glioma by Repressing Semaphorin 5A

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Rong [Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong (China); Department of Radiation Oncology, Fujian Medical University Union Hospital, Fuzhou, Fujian (China); Yao, Qiwei [Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong (China); Department of Radiation Oncology, Teaching Hospital of Fujian Medical University, Fujian Provincial Cancer Hospital, Fuzhou, Fujian (China); Ren, Chen; Liu, Ying; Yang, Hongli; Xie, Guozhu; Du, Shasha [Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong (China); Yang, Kaijun [Department of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong (China); Yuan, Yawei, E-mail: yuanyawei2015@outlook.com [Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong (China); Department of Radiation Oncology, Cancer Hospital Center of Guangzhou Medical University, Guangzhou, Guangdong (China)

    2016-11-15

    Purpose: Although increasing evidence has shown that long noncoding RNAs play an important regulatory role in carcinogenesis and tumor progression, little is known about the role of small nucleolar RNA host gene 18 (SNHG18) in cancer. The goal of this study was to investigate the expression of SNHG18 and its clinical significance in glioma. Methods and Materials: Differences in the lncRNA expression profile between M059K and M059J cells were assessed by lncRNA expression microarray analysis. The expression and localization of SNHG18 in glioma cells or tissues was evaluated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and in situ hybridization (ISH), respectively. the clinical associations of SNHG18 in glioma was evaluated by qRT-PCR, ISH and immunohistochemistry. The role of SNHG18 in glioma radiosensitivity was evaluated by colony formation assays, immunofluorescence, Western blot and tumor growth inhibition study. Results: The present study investigated the clinical associations of SNHG18 and its role in glioma. Our results showed that the expression of SNHG18 was remarkably upregulated in clinical glioma tissues compared with normal brain tissues. SNHG18 expression was associated with the clinical tumor grade and correlated negatively with isocitrate dehydrogenase 1 mutation. In addition, knockdown of SNHG18 with short hairpin RNA suppressed the radioresistance of glioma cells, and transgenic expression of SNHG18 had the opposite effect. Furthermore, xenograft tumors grown from cells with SNHG18 deletion were more radiosensitive than tumors grown from control cells. Further studies revealed that SNHG18 promotes radioresistance by inhibiting semaphorin 5A and that inhibition of semaphorin 5A expression abrogated the radiosensitizing effect caused by SNHG18 deletion. Conclusions: Our findings provide new insights into the role of SNHG18 in glioma and suggest its potential as a target for glioma therapy.

  13. Pim-3 contributes to radioresistance through regulation of the cell cycle and DNA damage repair in pancreatic cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Xiang-Yuan; Wang, Zhen [Cancer Research Institute, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai (China); Li, Bei [Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai (China); Zhang, Ying-Jian, E-mail: yjzhang111@aliyun.com [Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai (China); Li, Ying-Yi, E-mail: liyingyi@fudan.edu.cn [Cancer Research Institute, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai (China)

    2016-04-22

    Resistance of cancer cells to chemoradiotherapy is a major clinical problem in pancreatic cancer treatment. Therefore, understanding the molecular basis of cellular resistance and identifying novel targets are essential for improving treatment efficacy for pancreatic cancer patients. Previous studies have demonstrated a significant role for Pim-3 in pancreatic cancer survival against gemcitabine-induced genotoxic stress. Here, we observed that radiation treatment enhanced Pim-3 expression in human pancreatic cancer cells in vitro. Stable overexpression of Pim-3 in pancreatic cancer cells significantly protected cells against radiation treatment by attenuating G2/M phase cell cycle arrest and DNA damage response. Silencing of Pim-3 expression significantly elevated the phosphorylation of histone variant H2AX, a marker of DNA double strand breaks, and decreased the activation of ataxia-telangiectasia-mutated (ATM) kinase, along with its downstream targets, eventually enhancing the radiosensitivity of human pancreatic cancer cells in vitro and in vivo. Hence, we demonstrated a novel function for Pim-3 in human pancreatic cancer cell survival against radiation. Targeting Pim-3 may be a promising way to improve treatment efficacy in combination with radiotherapy in human pancreatic cancer. - Highlights: • This is first study to demonstrate that Pim-3 is endogenously induced by ionizing radiation in pancreatic cancer cells, and Pim-3 overexpression enhanced radioresistance of pancreatic cancer cells both in vitro and in vivo. • This is first study to provide evidence that radioresistance induced by Pim-3 is mainly attributed to Pim-3 induces activation of ATM, which subsequently activates checkpoint 1, leading to amplification of DNA repair through cell cycle arrest and DNA repair pathways. • This is first study to indicate that targeting Pim-3 may be a promising strategy to provide better treatment efficacy in combination with radiotherapy in human pancreatic

  14. KNK437, abrogates hypoxia-induced radioresistance by dual targeting of the AKT and HIF-1α survival pathways

    International Nuclear Information System (INIS)

    Oommen, Deepu; Prise, Kevin M.

    2012-01-01

    Highlights: ► KNK437, a benzylidene lactam compound, is a novel radiosensitizer. ► KNK437 inhibits AKT signaling and abrogates the accumulation of HIF-1α under hypoxia. ► KNK437 abrogates hypoxia induced resistance to radiation. -- Abstract: KNK437 is a benzylidene lactam compound known to inhibit stress-induced synthesis of heat shock proteins (HSPs). HSPs promote radioresistance and play a major role in stabilizing hypoxia inducible factor-1α (HIF-1α). HIF-1α is widely responsible for tumor resistance to radiation under hypoxic conditions. We hypothesized that KNK437 sensitizes cancer cells to radiation and overrides hypoxia-induced radioresistance via destabilizing HIF-1α. Treatment of human cancer cells MDA-MB-231 and T98G with KNK437 sensitized them to ionizing radiation (IR). Surprisingly, IR did not induce HSPs in these cell lines. As hypothesized, KNK437 abrogated the accumulation of HIF-1α in hypoxic cells. However, there was no induction of HSPs under hypoxic conditions. Moreover, the proteosome inhibitor MG132 did not restore HIF-1α levels in KNK437-treated cells. This suggested that the absence of HIF-1α in hypoxic cells was not due to the enhanced protein degradation. HIF-1α is mainly regulated at the level of post-transcription and AKT is known to modulate the translation of HIF-1α mRNA. Interestingly, pre-treatment of cells with KNK437 inhibited AKT signaling. Furthermore, down regulation of AKT by siRNA abrogated HIF-1α levels under hypoxia. Interestingly, KNK437 reduced cell survival in hypoxic conditions and inhibited hypoxia-induced resistance to radiation. Taken together, these data suggest that KNK437 is an effective radiosensitizer that targets multiple pro-survival stress response pathways.

  15. Radioresistant head and neck squamous cell carcinoma cells: Intracellular signaling, putative biomarkers for tumor recurrences and possible therapeutic targets

    International Nuclear Information System (INIS)

    Skvortsov, Sergej; Jimenez, Connie R.; Knol, Jaco C.; Eichberger, Paul; Schiestl, Bernhard; Debbage, Paul; Skvortsova, Ira; Lukas, Peter

    2011-01-01

    Purpose: Treatment of local and distant head and neck cancer recurrences after radiotherapy remains an unsolved problem. In order to identify potential targets for use in effective therapy of recurrent tumors, we have investigated protein patterns in radioresistant (FaDu-IRR and SCC25-IRR, “IRR cells”) as compared to parental (FaDu and SCC25) head and neck carcinoma cells. Methods and materials: Radiation resistant IRR cells were derived from parental cells after repeated exposure to ionizing radiation 10 times every two weeks at a single dose of 10 Gy, resulting in a total dose of 100 Gy. Protein profiling in parental and IRR cells was carried out using two-dimensional differential gel electrophoresis (2D-DIGE) followed by MALDI-TOF/TOF mass spectrometry. Cell viability, cell migration assays and Western blot analysis were used to confirm results obtained using the proteome approach. Results: Forty-five proteins that were similarly modulated in FaDu-IRR and SCC25-IRR cells compared to parental cells were selected to analyze their common targets. It was found that these either up- or down-regulated proteins are closely related to the enhancement of cell migration which is regulated by Rac1 protein. Further investigations confirmed that Rac1 is up-regulated in IRR cells, and inhibiting its action reduces the migratory abilities of these cells. Additionally, the Rac1 inhibitor exerts cytostatic effects in HNSCC cells, mostly in migratory cells. Conclusions: Based on these results, we conclude that radioresistant HNSCC cells possess enhanced metastatic abilities that are regulated by a network of migration-related proteins. Rac1 protein may be considered as a putative biomarker of HNSCC radiation resistance, and as a potential therapeutic target for treating local and distant HNSCC recurrences.

  16. Pim-3 contributes to radioresistance through regulation of the cell cycle and DNA damage repair in pancreatic cancer cells

    International Nuclear Information System (INIS)

    Chen, Xiang-Yuan; Wang, Zhen; Li, Bei; Zhang, Ying-Jian; Li, Ying-Yi

    2016-01-01

    Resistance of cancer cells to chemoradiotherapy is a major clinical problem in pancreatic cancer treatment. Therefore, understanding the molecular basis of cellular resistance and identifying novel targets are essential for improving treatment efficacy for pancreatic cancer patients. Previous studies have demonstrated a significant role for Pim-3 in pancreatic cancer survival against gemcitabine-induced genotoxic stress. Here, we observed that radiation treatment enhanced Pim-3 expression in human pancreatic cancer cells in vitro. Stable overexpression of Pim-3 in pancreatic cancer cells significantly protected cells against radiation treatment by attenuating G2/M phase cell cycle arrest and DNA damage response. Silencing of Pim-3 expression significantly elevated the phosphorylation of histone variant H2AX, a marker of DNA double strand breaks, and decreased the activation of ataxia-telangiectasia-mutated (ATM) kinase, along with its downstream targets, eventually enhancing the radiosensitivity of human pancreatic cancer cells in vitro and in vivo. Hence, we demonstrated a novel function for Pim-3 in human pancreatic cancer cell survival against radiation. Targeting Pim-3 may be a promising way to improve treatment efficacy in combination with radiotherapy in human pancreatic cancer. - Highlights: • This is first study to demonstrate that Pim-3 is endogenously induced by ionizing radiation in pancreatic cancer cells, and Pim-3 overexpression enhanced radioresistance of pancreatic cancer cells both in vitro and in vivo. • This is first study to provide evidence that radioresistance induced by Pim-3 is mainly attributed to Pim-3 induces activation of ATM, which subsequently activates checkpoint 1, leading to amplification of DNA repair through cell cycle arrest and DNA repair pathways. • This is first study to indicate that targeting Pim-3 may be a promising strategy to provide better treatment efficacy in combination with radiotherapy in human pancreatic

  17. Upregulation of Long Noncoding RNA Small Nucleolar RNA Host Gene 18 Promotes Radioresistance of Glioma by Repressing Semaphorin 5A

    International Nuclear Information System (INIS)

    Zheng, Rong; Yao, Qiwei; Ren, Chen; Liu, Ying; Yang, Hongli; Xie, Guozhu; Du, Shasha; Yang, Kaijun; Yuan, Yawei

    2016-01-01

    Purpose: Although increasing evidence has shown that long noncoding RNAs play an important regulatory role in carcinogenesis and tumor progression, little is known about the role of small nucleolar RNA host gene 18 (SNHG18) in cancer. The goal of this study was to investigate the expression of SNHG18 and its clinical significance in glioma. Methods and Materials: Differences in the lncRNA expression profile between M059K and M059J cells were assessed by lncRNA expression microarray analysis. The expression and localization of SNHG18 in glioma cells or tissues was evaluated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and in situ hybridization (ISH), respectively. the clinical associations of SNHG18 in glioma was evaluated by qRT-PCR, ISH and immunohistochemistry. The role of SNHG18 in glioma radiosensitivity was evaluated by colony formation assays, immunofluorescence, Western blot and tumor growth inhibition study. Results: The present study investigated the clinical associations of SNHG18 and its role in glioma. Our results showed that the expression of SNHG18 was remarkably upregulated in clinical glioma tissues compared with normal brain tissues. SNHG18 expression was associated with the clinical tumor grade and correlated negatively with isocitrate dehydrogenase 1 mutation. In addition, knockdown of SNHG18 with short hairpin RNA suppressed the radioresistance of glioma cells, and transgenic expression of SNHG18 had the opposite effect. Furthermore, xenograft tumors grown from cells with SNHG18 deletion were more radiosensitive than tumors grown from control cells. Further studies revealed that SNHG18 promotes radioresistance by inhibiting semaphorin 5A and that inhibition of semaphorin 5A expression abrogated the radiosensitizing effect caused by SNHG18 deletion. Conclusions: Our findings provide new insights into the role of SNHG18 in glioma and suggest its potential as a target for glioma therapy.

  18. Does the cell radioresistance acquired by low dose-rate gamma irradiation depend on genetic factors or physiological changes. Study carried out on inactive cells of the unicellular green alga Chlorella pyrenoidosa CHICK

    International Nuclear Information System (INIS)

    Dettwiller, Pascale.

    1982-09-01

    Inactive cells of the unicellular green alga Chlorella pyrenoidosa CHICK were used to test the following hypothesis: the radioresistance acquired by these cells after irradiation at low dose rate (0.06 Gy/mn) is due to the selection or induction of radioresistant clones. Clone cultures were grown mainly from colonies exhibiting defects (high cell loss, slowed growth, pigment deficiency). Of thirty clones studied, three only of second and third separations possessed the radioresistance of their original population. On the basis of these results, backed up by a first experiment which shows the loss of cell radioresistance when continuous irradiation is stopped, the initial hypothesis may be dismissed and research directed towards changes relative to cell restoration processes by irradiation at low dose rates [fr

  19. Molecular and functional analysis of DIR1; a novel gene with a potential role in induced radioresistance

    International Nuclear Information System (INIS)

    Young, S.M.; McKeen, H.; Valentine, A.; Burke, G.; Hirst, D.; Robson, T.

    2003-01-01

    Full text: There is now little doubt about the existence of radioprotective mechanisms that are upregulated following exposure to small doses of ionizing radiation and other DNA-damaging agents. The identification of genes whose expression is altered following exposure to a low dose of ionizing radiation will be an important step in understanding these phenomena. We have identified a novel gene, DIR1, that is transiently repressed by low radiation doses (Robson et al.,1997 and 1999) and is otherwise expressed in a wide range of cell lines and tissues. The repression of this gene is in the dose range where induced radioresistance is observed in a number of cell survival studies (Joiner et al., 2001) implicating this gene in induced radioresistance. Using antisense strategies, we have demonstrated that the DIR1 gene product appears to be involved in cell survival and DNA repair in a range of cell lines following exposure to X-rays (Robson et al., 1999 and 2000). Using microchip array analysis we have been able to identify a number of genes activated as a consequence of DIR1 repression. Preliminary data implicate genes involved in repair, cell cycle and stress response and include ATM and BRCA2. We are now confirming these responses using northern and western blot analysis. Yeast two hybrid analysis has also been useful in demonstrating interacting proteins. One protein, which interacts with DIR1 is similar to murine UIP28, a RING finger protein which interacts with the ubiquitin conjugating enzyme, UbcM4. Interestingly, the ubiquitin (Ub)/proteosome pathway regulates many cellular processes including apoptosis, cell cycle progression, stress responses, development and transcriptional regulation. Further characterisation of these downstream genes and interacting proteins will allow us to:- i) dissect the cellular pathways involved in adaptation to oxidative and genotoxic stress ii) elucidate the mechanisms involved in many disease pathologies iii) identify new

  20. Decursin reduce radio-resistance of hypoxic regions under the proton beam therapy by induced HIF-1α degradation

    International Nuclear Information System (INIS)

    Jung, Myung Hwan; Kim, Kye Ryung

    2013-01-01

    Protons induce cancer-cell apoptosis in vitro and block blood vessel formation in vivo through the generation of reactive oxygen species (ROS). The fact that proton severely inhibits blood vessel development in zebrafish embryos suggests a higher sensitivity of vascular endothelial cells to proton beam. Decursin, a coumarin compound, was originally isolated from Angelica gigas Nakai (Dang Gui). A. gigas root has been traditionally used in Korean folk medicine for the treatment of anemia and other common diseases. In previous reports, decursin was reported to exhibit anti-tumor activity against various cancer cells and to inhibit the activities of the androgen and androgen-receptor (AR) signaling pathway in prostate cancer, induction of cell cycle arrest and apoptosis in various cancer cells, such as prostate, breast, bladder, and colon cancer cells. Decursin also inhibits VEGF-induced angiogenesis through the suppression of the VEGFR-2-signaling pathway. However, the mechanism of decursin mediates change of HIF-1α activities is not clear. In this research, we identified regulations of the HIF-1α and the anti-angiogenesis effects of decursin in proton-beam-irradiated human lung cancer, prostate cancer and Hepatic cancer cells. We investigated the underlying mechanisms of positive effects of protonbeam-induced anti-angiogenesis. Our data indicate that the groups co-treated with decursin and a proton-beam had significant reduced HIF-1α activity compared with the groups treated with only a proton beam under the hypoxic condition caused by DFX(desferrioxamine). Decursin was found to induced HIF-1α degradation. Therefore, we suggest that decursin may be a potential candidate for use as a sensitizer for proton-beaminduced cell apoptosis. Here we have shown that decursin successfully reduced HIF-1α stability under hypoxic condition by induced desferrioxamine. We showed novel candidates for anti-angiogenic compound, decursin, leading to complete inhibition of radio-resistance

  1. Decursin reduce radio-resistance of hypoxic regions under the proton beam therapy by induced HIF-1α degradation

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Myung Hwan; Kim, Kye Ryung [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2013-10-15

    Protons induce cancer-cell apoptosis in vitro and block blood vessel formation in vivo through the generation of reactive oxygen species (ROS). The fact that proton severely inhibits blood vessel development in zebrafish embryos suggests a higher sensitivity of vascular endothelial cells to proton beam. Decursin, a coumarin compound, was originally isolated from Angelica gigas Nakai (Dang Gui). A. gigas root has been traditionally used in Korean folk medicine for the treatment of anemia and other common diseases. In previous reports, decursin was reported to exhibit anti-tumor activity against various cancer cells and to inhibit the activities of the androgen and androgen-receptor (AR) signaling pathway in prostate cancer, induction of cell cycle arrest and apoptosis in various cancer cells, such as prostate, breast, bladder, and colon cancer cells. Decursin also inhibits VEGF-induced angiogenesis through the suppression of the VEGFR-2-signaling pathway. However, the mechanism of decursin mediates change of HIF-1α activities is not clear. In this research, we identified regulations of the HIF-1α and the anti-angiogenesis effects of decursin in proton-beam-irradiated human lung cancer, prostate cancer and Hepatic cancer cells. We investigated the underlying mechanisms of positive effects of protonbeam-induced anti-angiogenesis. Our data indicate that the groups co-treated with decursin and a proton-beam had significant reduced HIF-1α activity compared with the groups treated with only a proton beam under the hypoxic condition caused by DFX(desferrioxamine). Decursin was found to induced HIF-1α degradation. Therefore, we suggest that decursin may be a potential candidate for use as a sensitizer for proton-beaminduced cell apoptosis. Here we have shown that decursin successfully reduced HIF-1α stability under hypoxic condition by induced desferrioxamine. We showed novel candidates for anti-angiogenic compound, decursin, leading to complete inhibition of radio-resistance

  2. High linear-energy-transfer radiation can overcome radioresistance of glioma stem-like cells to low linear-energy-transfer radiation.

    Science.gov (United States)

    Hirota, Yuki; Masunaga, Shin-Ichiro; Kondo, Natsuko; Kawabata, Shinji; Hirakawa, Hirokazu; Yajima, Hirohiko; Fujimori, Akira; Ono, Koji; Kuroiwa, Toshihiko; Miyatake, Shin-Ichi

    2014-01-01

    Ionizing radiation is applied as the standard treatment for glioblastoma multiforme (GBM). However, radiotherapy remains merely palliative, not curative, because of the existence of glioma stem cells (GSCs), which are regarded as highly radioresistant to low linear-energy-transfer (LET) photons. Here we analyzed whether or not high-LET particles can overcome the radioresistance of GSCs. Glioma stem-like cells (GSLCs) were induced from the GBM cell line A172 in stem cell culture medium. The phenotypes of GSLCs and wild-type cells were confirmed using stem cell markers. These cells were irradiated with (60)Co gamma rays or reactor neutron beams. Under neutron-beam irradiation, high-LET proton particles can be produced through elastic scattering or nitrogen capture reaction. Radiosensitivity was assessed by a colony-forming assay, and the DNA double-strand breaks (DSBs) were assessed by a histone gamma-H2AX focus detection assay. In stem cell culture medium, GSLCs could form neurosphere-like cells and express neural stem cell markers (Sox2 and Musashi) abundantly in comparison with their parental cells. GSLCs were significantly more radioresistant to gamma rays than their parental cells, but neutron beams overcame this resistance. There were significantly fewer gamma-H2AX foci in the A172 GSLCs 24 h after irradiation with gamma rays than in their parental cultured cells, while there was no apparent difference following neutron-beam irradiation. High-LET radiation can overcome the radioresistance of GSLCs by producing unrepairable DNA DSBs. High-LET radiation therapy might have the potential to overcome GBM's resistance to X-rays in a clinical setting.

  3. High linear-energy-transfer radiation can overcome radioresistance of glioma stem-like cells to low linear-energy-transfer radiation

    International Nuclear Information System (INIS)

    Hirota, Yuki; Kawabata, Shinji; Kuroiwa, Toshihiko; Miyatake, Shin-ichi; Masunaga, Shin-ichiro; Kondo, Natsuko; Ono, Koji; Hirakawa, Hirokazu; Yajima, Hirohiko; Fujimori, Akira

    2014-01-01

    Ionizing radiation is applied as the standard treatment for glioblastoma multiforme (GBM). However, radiotherapy remains merely palliative, not curative, because of the existence of glioma stem cells (GSCs), which are regarded as highly radioresistant to low linear-energy-transfer (LET) photons. Here we analyzed whether or not high-LET particles can overcome the radioresistance of GSCs. Glioma stem-like cells (GSLCs) were induced from the GBM cell line A172 in stem cell culture medium. The phenotypes of GSLCs and wild-type cells were confirmed using stem cell markers. These cells were irradiated with 60 Co gamma rays or reactor neutron beams. Under neutron-beam irradiation, high-LET proton particles can be produced through elastic scattering or nitrogen capture reaction. Radiosensitivity was assessed by a colony-forming assay, and the DNA double-strand breaks (DSBs) were assessed by a histone gamma-H2AX focus detection assay. In stem cell culture medium, GSLCs could form neurosphere-like cells and express neural stem cell markers (Sox2 and Musashi) abundantly in comparison with their parental cells. GSLCs were significantly more radioresistant to gamma rays than their parental cells, but neutron beams overcame this resistance. There were significantly fewer gamma-H2AX foci in the A172 GSLCs 24 h after irradiation with gamma rays than in their parental cultured cells, while there was no apparent difference following neutron-beam irradiation. High-LET radiation can overcome the radioresistance of GSLCs by producing unrepairable DNA DSBs. High-LET radiation therapy might have the potential to overcome GBM's resistance to X-rays in a clinical setting. (author)

  4. HDAC4 and HDAC6 sustain DNA double strand break repair and stem-like phenotype by promoting radioresistance in glioblastoma cells.

    Science.gov (United States)

    Marampon, Francesco; Megiorni, Francesca; Camero, Simona; Crescioli, Clara; McDowell, Heather P; Sferra, Roberta; Vetuschi, Antonella; Pompili, Simona; Ventura, Luca; De Felice, Francesca; Tombolini, Vincenzo; Dominici, Carlo; Maggio, Roberto; Festuccia, Claudio; Gravina, Giovanni Luca

    2017-07-01

    The role of histone deacetylase (HDAC) 4 and 6 in glioblastoma (GBM) radioresistance was investigated. We found that tumor samples from 31 GBM patients, who underwent temozolomide and radiotherapy combined treatment, showed HDAC4 and HDAC6 expression in 93.5% and 96.7% of cases, respectively. Retrospective clinical data analysis demonstrated that high-intensity HDAC4 and/or HDAC6 immunostaining was predictive of poor clinical outcome. In vitro experiments revealed that short hairpin RNA-mediated silencing of HDAC4 or HDAC6 radiosensitized U87MG and U251MG GBM cell lines by promoting DNA double-strand break (DSBs) accumulation and by affecting DSBs repair molecular machinery. We found that HDAC6 knock-down predisposes to radiation therapy-induced U251MG apoptosis- and U87MG autophagy-mediated cell death. HDAC4 silencing promoted radiation therapy-induced senescence, independently by the cellular context. Finally, we showed that p53 WT expression contributed to the radiotherapy lethal effects and that HDAC4 or HDAC6 sustained GBM stem-like radioresistant phenotype. Altogether, these observations suggest that HDAC4 and HDAC6 are guardians of irradiation-induced DNA damages and stemness, thus promoting radioresistance, and may represent potential prognostic markers and therapeutic targets in GBM. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Prognostic factors for outcomes after whole-brain irradiation of brain metastases from relatively radioresistant tumors: a retrospective analysis

    Directory of Open Access Journals (Sweden)

    Schild Steven E

    2010-10-01

    Full Text Available Abstract Background This study investigated potential prognostic factors in patients treated with whole-brain irradiation (WBI alone for brain metastases from relatively radioresistant tumors such as malignant melanoma, renal cell carcinoma, and colorectal cancer. Additionally, a potential benefit from escalating the radiation dose was investigated. Methods Data from 220 patients were retrospectively analyzed for overall survival and local control. Nine potential prognostic factors were evaluated: tumor type, WBI schedule, age, gender, Karnofsky performance score, number of brain metastases, extracerebral metastases, interval from diagnosis of cancer to WBI, and recursive partitioning analysis (RPA class. Results Survival rates at 6 and 12 months were 32% and 19%, respectively. In the multivariate analysis, WBI doses >30 Gy (p = 0.038, KPS ≥70 (p Conclusions Improved outcomes were associated with WBI doses >30 Gy, better performance status, fewer brain metastases, lack of extracerebral metastases, and lower RPA class. Patients receiving WBI alone appear to benefit from WBI doses >30 Gy. However, such a benefit is limited to RPA class 1 or 2 patients.

  6. Natural cytotoxicity in immunodeficiency diseases: preservation of natural killer activity and the in vivo appearance of radioresistant killing

    International Nuclear Information System (INIS)

    Pierce, G.F.; Polmar, S.H.; Schacter, B.Z.; Brovall, C.; Hornick, D.L.; Sorensen, R.U.

    1986-01-01

    We studied spontaneous natural killer (NK) cell activity and radiation-resistant NK mediated cytotoxicity in four patients with clinically documented severe combined immune deficiency disease (SCID), and in one subject each with intestinal lymphangiectasia and cartilage-hair hypoplasia. We observed the preservation of spontaneous NK activity in all patients despite the presence of profound B- and T-lymphocytopenia and clinical immunodeficiency. NK activity was associated with relatively normal circulating numbers of OKM1+ lymphocytes, a population known to contain NK effectors. Spontaneous NK activity resistant to 3000 rad was increased in all patients, indicating the presence of activated natural killer cells in vivo. The concept of a chronically activated immune system in these patients was further supported by the presence of increased Ia positive T cells in all subjects tested, suggesting that radioresistant NK activity may be a useful parameter to measure when assessing in vivo immune activation. Our data, as well as that of others, supports the hypothesis that at least one population of NK cells is a distinct lineage arising at the differentiation level of myeloid and lymphoid stem cells in the bone marrow

  7. Prenatal diagnosis of ataxia-telangiectasia and Nijmegen Breakage Syndrome by the assay of radioresistant DNA synthesis

    International Nuclear Information System (INIS)

    Kleijer, W.J.; Kraan, M. van der; Los, F.J.; Jaspers, N.G.J.

    1994-01-01

    Prenatal diagnosis was performed in 16 pregnancies at risk of ataxia-telangiectasia (A-T) or Nijmegen Breakage Syndrome (NBS). Radioresistant DNA synthesis (RDS) was investigated in cultured chorionic villus (CV) cells and/or amniotic fluid (AF) cells. In four pregnancies, an affected foetus was diagnosed with increased RDS in cultured CV cells. In three of the four cases confirmation of the diagnosis was obtained by analysis of AF cells and/or skin fibroblasts from the foetus cultured after termination of the pregnancy; in the fourth case a fibroblast culture from the aborted foetus failed. In one case, only AF cells could be analysed in a late stage of pregnancy; pregnancy was terminated due to intermediate/equivocal results but the foetus fibroblasts showed normal RDS. Normal RDS was demonstrated in the other 11 pregnancies at 25% risk either by analysis of CB cells (nine cases) or of AF cells (two cases). In some cases the (normal) results on the CV cells were corroborated by subsequent analysis of Af cells. The results suggest that RDS analysis of CV cells allows reliable prenatal diagnosis of A-T/NBS. However, amniocentesis may be necessary to confirm normal results on CV cells if the foetus is female (because of the risk of maternal cell contamination) or in the rare case of equivocal results. (author)

  8. Autodigestion of chromatin in some radiosensitive and radioresistant mouse cells. Role of proteolysis and endonucleolysis

    International Nuclear Information System (INIS)

    Suciu, D.; Bojan, O.

    1981-01-01

    Evidence is presented indicating that mouse thymus, spleen, kidney, lung and heart contain a protease activity with relatively high specificity for histones. It is suggested that degradation of chromatin occurring in irradiated lymphoid tissues is produced by the action of alkaline endonuclease in association with this histone protease. The autodigestion of chromatin was assessed by determining the release of soluble chromatin from cells suspended in sucrose media of low ionic strength. It was found that the protease inhibitors, phenylmethylsulphonyl fluoride and especially NaHSO 3 , were also capable of depressing the activity of alkaline endonuclease, the fragmentation of chromatin, and the release of soluble chromatin. The results suggest that the release of histones from irradiated lymphoid tissues cannot be considered as a determinant step in the fragmentation of DNA in chromatin. (author)

  9. 31P NMR spectroscopy and HbO2 cryospectrophotometry in prediction of tumor radioresistance caused by hypoxia.

    Science.gov (United States)

    Rofstad, E K; DeMuth, P; Fenton, B M; Ceckler, T L; Sutherland, R M

    1989-04-01

    The aim of this study was to search for possible relationships between the fraction of radiobiologically hypoxic cells in tumors and their 31P NMR spectral parameters and intracapillary HbO2 saturations. Four different tumor lines, two murine sarcomas (KHT, RIF-1) and two human ovarian carcinoma xenografts (MLS, OWI), were used. When tumor volume increased from about 200 mm3 to about 2000 mm3, hypoxic fraction increased from 12 to 23% for the KHT line, from 0.9 to 1.7% for the RIF-1 line, and from 9 to 28% for the MLS line. The OWI line showed similar hypoxic fractions at 200 (17%) and 2000 mm3 (15%). Tumor bioenergetic status decreased, that is, the inorganic phosphate (Pi) resonance increased and the phosphocreatine (PCr) and nucleoside triphosphate beta (NTP beta) resonances decreased, with increasing tumor volume for the KHT, RIF-1, and MLS lines, whereas the OWI line did not show any changes in the 31P NMR spectral parameters during tumor growth. Similarly, tumor HbO2 saturation status, that is, the fraction of vessels with HbO2 saturation above 30%, decreased with increasing tumor volume for the KHT, RIF-1, and MLS lines, but remained unchanged during tumor growth for the OWI line. Although the data indicated a relationship between hypoxic fraction and tumor bioenergetic status as well as tumor HbO2 saturation status within a specific line during tumor growth, there was no correlation between hypoxic fraction and tumor bioenergetic status or tumor HbO2 saturation status across the four tumor lines. This may have occurred because cell survival time under hypoxic stress as well as fraction of non-clonogenic, but metabolically active hypoxic cells differed among the tumor lines. This indicates that 31P NMR spectroscopy and HbO2 cryospectrophotometry data have to be supplemented with other data to be useful in prediction of tumor radioresistance caused by hypoxia.

  10. Differential Bystander Signaling Between Radioresistant Chondrosarcoma Cells and Fibroblasts After X-Ray, Proton, Iron Ion and Carbon Ion Exposures

    Energy Technology Data Exchange (ETDEWEB)

    Wakatsuki, Masaru, E-mail: wa@mbe.nifty.com [Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan); Department of Radiation Oncology, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts (United States); Magpayo, Nicole; Kawamura, Hidemasa; Held, Kathryn D. [Department of Radiation Oncology, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts (United States)

    2012-09-01

    Purpose: Chondrosarcoma is well known as a radioresistant tumor, but the mechanisms underlying that resistance are still unclear. The bystander effect is well documented in the field of radiation biology. We investigated the bystander response induced by X-rays, protons, carbon ions, and iron ions in chondrosarcoma cells using a transwell insert co-culture system that precludes physical contact between targeted and bystander cells. Methods and Materials: Human chondrosarcoma cells were irradiated with 0.1-, 0.5-, 1-, and 2-Gy X-rays, protons, carbon ions or iron ions using a transwell insert co-culture system. Formation of micronuclei and p53 binding protein 1 staining in bystander and irradiated cells were analyzed and bystander signaling between mixed cultures of chondrosarcoma cells, and normal human skin fibroblasts was investigated. Results: In this study, we show that the fraction of cells with DNA damages in irradiated chondrosarcoma cells showed dose-dependent increases with all beams. However, the fraction of cells with DNA damages in all bystander chondrosarcoma cells did not show any change from the levels in control cells. In the bystander signaling between mixed cultures of chondrosarcoma cells and fibroblasts, the amount of micronucleus formation in all bystander chondrosarcoma cells co-cultured with irradiated fibroblasts were the same as the levels for control cells. However, all bystander fibroblasts co-cultured with irradiated chondrosarcoma cells showed significant increases in the fraction of micronucleated cells compared to the rate of control cells. Conclusions: We conclude that chondrosarcoma cells in the transwell insert co-culture system could release bystander stimulations but could not develop bystander responses.

  11. Differential Bystander Signaling Between Radioresistant Chondrosarcoma Cells and Fibroblasts After X-Ray, Proton, Iron Ion and Carbon Ion Exposures

    International Nuclear Information System (INIS)

    Wakatsuki, Masaru; Magpayo, Nicole; Kawamura, Hidemasa; Held, Kathryn D.

    2012-01-01

    Purpose: Chondrosarcoma is well known as a radioresistant tumor, but the mechanisms underlying that resistance are still unclear. The bystander effect is well documented in the field of radiation biology. We investigated the bystander response induced by X-rays, protons, carbon ions, and iron ions in chondrosarcoma cells using a transwell insert co-culture system that precludes physical contact between targeted and bystander cells. Methods and Materials: Human chondrosarcoma cells were irradiated with 0.1-, 0.5-, 1-, and 2-Gy X-rays, protons, carbon ions or iron ions using a transwell insert co-culture system. Formation of micronuclei and p53 binding protein 1 staining in bystander and irradiated cells were analyzed and bystander signaling between mixed cultures of chondrosarcoma cells, and normal human skin fibroblasts was investigated. Results: In this study, we show that the fraction of cells with DNA damages in irradiated chondrosarcoma cells showed dose-dependent increases with all beams. However, the fraction of cells with DNA damages in all bystander chondrosarcoma cells did not show any change from the levels in control cells. In the bystander signaling between mixed cultures of chondrosarcoma cells and fibroblasts, the amount of micronucleus formation in all bystander chondrosarcoma cells co-cultured with irradiated fibroblasts were the same as the levels for control cells. However, all bystander fibroblasts co-cultured with irradiated chondrosarcoma cells showed significant increases in the fraction of micronucleated cells compared to the rate of control cells. Conclusions: We conclude that chondrosarcoma cells in the transwell insert co-culture system could release bystander stimulations but could not develop bystander responses.

  12. The activity of catalase and superoxide dismutase in isogenous bacteria strains with different radioresistance

    International Nuclear Information System (INIS)

    Vasil'eva, E.I.; Goncharenko, E.N.; Yudz, T.I.; Samojlenko, I.I.

    1984-01-01

    The catalase and superoxide dismutase activity in isogenous bacterial strains with various radiosensitivity is investigated. In micrococcus radiodurans mutants with defects in the DNA repair systems the superoxide dismutase activity is lower than in the wild type cells. In investigated Escherichia coli strains differing in radiosensitivity, no alteration in catalase and superoxide dismutase activity is found. The conclusion is drawn that viability of bacteria subjected to the effect of ionizing radiations is determined by the efficiency of DNA repair systems whose functional reliability is sometimes connected with the catalase and suferoxide dismutase activity

  13. Radiation-induced phosphorylation of P53 protects radioresistant Spodoptera frugiperda 9 cells by suppressing microRNA-31-Bim-Bax mediated apoptosis

    International Nuclear Information System (INIS)

    Kumar, Ashish; Chandna, Sudhir

    2016-01-01

    In this study, we demonstrate the role of microRNA-31 (miR-31) in the regulation of radiation-induced apoptosis in model radioresistant insect cell line Sf9 (derived from the ovaries of insect Spodoptera frugiperda) which carries well-conserved apoptotic response. We also investigated the miR-31 expression regulation by p53 homologue in these cells. Our initial in silico analysis confirmed perfect conservation of mature miR-31 across various insect orders, hence we designed biotinylated probes from Bombyx mori sequence for successful detection of miR-31 in Sf9 cells

  14. Comparison of SDR presumed by AAMI and the radio-resistance distribution of the microbiological populations exist on the Turkish made single use syringes

    International Nuclear Information System (INIS)

    Konac, T.; Siyakus, G.; Basguel, M.; Uenal, Z.

    2001-01-01

    The concept of radiation sterilization of medical devices was introduced in Turkey 10 years ago through the irradiation facilities in Ankara and Istanbul. It has been preferred by international community due to technological advantages,such as freedom from chemical residues, safer sterility assurance, etc.. This technology is regulated by ISO 11137 (1), EN 552 (2) standards and their references. The scope of this study was to compare the radio-resistance distribution of the microbial population on the Turkish single use syringes and SDR

  15. Radioresistance of microorganisms in sewage sludge with special regard to the virus species

    International Nuclear Information System (INIS)

    Mayr, A.; Mahnel, H.; Brodorotti, H.S. v.; Ottis, K.

    1979-01-01

    Of the viral species present in surface and waste water only entero-, reo-, parvo-, and possibly paramyxoviruses are of relevance. These viruses remain infectious through to the sewage sludge stage, although then only present in small numbers. Bacteria and moulds are present in high concentrations in sewage sludge, the majority being non-pathogenis or only facultative pathogenic species. Of these only Salmonellae are of public health concern. Viruses are considerably more radiation resistant than bacteria and moulds. In sewage sludge a parvo virus was clearly the most resistant towards radiation followed, in order of decreasing resistivity, by reo- and entero-viruses. With the exception of the strongly resistant streptococcus faecalis two enterobacteria and one mould were found to be relatively radiation-sensitive. Gamma radiation is effective for inactivating all viral and bacterial contamination of sewage sludge. The dose required depends upon the radiation resistance and concentration of the individual strain. Enteroviral elimination determines the dose required for viruses and salmonella radiation the dose for bacteria. For practical sewage sludge decontamination a total irradiation dose of 500 krad has been calculated to meet normal requirements, and this dose can be raised to 1 Mrad for more stringent demands. (orig./MG) [de

  16. APOBEC3G enhances lymphoma cell radioresistance by promoting cytidine deaminase-dependent DNA repair.

    Science.gov (United States)

    Nowarski, Roni; Wilner, Ofer I; Cheshin, Ori; Shahar, Or D; Kenig, Edan; Baraz, Leah; Britan-Rosich, Elena; Nagler, Arnon; Harris, Reuben S; Goldberg, Michal; Willner, Itamar; Kotler, Moshe

    2012-07-12

    APOBEC3 proteins catalyze deamination of cytidines in single-stranded DNA (ssDNA), providing innate protection against retroviral replication by inducing deleterious dC > dU hypermutation of replication intermediates. APOBEC3G expression is induced in mitogen-activated lymphocytes; however, no physiologic role related to lymphoid cell proliferation has yet to be determined. Moreover, whether APOBEC3G cytidine deaminase activity transcends to processing cellular genomic DNA is unknown. Here we show that lymphoma cells expressing high APOBEC3G levels display efficient repair of genomic DNA double-strand breaks (DSBs) induced by ionizing radiation and enhanced survival of irradiated cells. APOBEC3G transiently accumulated in the nucleus in response to ionizing radiation and was recruited to DSB repair foci. Consistent with a direct role in DSB repair, inhibition of APOBEC3G expression or deaminase activity resulted in deficient DSB repair, whereas reconstitution of APOBEC3G expression in leukemia cells enhanced DSB repair. APOBEC3G activity involved processing of DNA flanking a DSB in an integrated reporter cassette. Atomic force microscopy indicated that APOBEC3G multimers associate with ssDNA termini, triggering multimer disassembly to multiple catalytic units. These results identify APOBEC3G as a prosurvival factor in lymphoma cells, marking APOBEC3G as a potential target for sensitizing lymphoma to radiation therapy.

  17. Molecular cloning and analysis of DNA repair gene from the radioresistant bacterium deinococcus radiodurans

    International Nuclear Information System (INIS)

    Du Zeji; Wang Mingsuo

    1998-12-01

    Deinococcus radiodurans (Dr) possesses a prominent ability to repair DNA injury induced by various DNA-damaging agents including mitomycin C (MC), ultraviolet light (UV) and ionizing radiation. A DNA repair mutant Dr KH3111 is a streptomycin resistant (Sm R ) derivative of KH311 which is generated by treatment with nitrosoguanidine and is sensitive to MC, 8-trimethyl-psoralen, UV and γ-ray irradiation. Gene affected by a mutation in the mutant is identified and its nucleotide sequence is determined. A complete open reading frame (ORF) which encompassed the KH3111 mutation region is found and tentatively designated as orf144b. The deduced amino acid (aa) sequence of orf144b consists of 284 aa and has no significant homology to other known proteins. The exact KH3111 mutation site is one nucleotide altered (G to A) in the sequence of orf144b in the mutant. The KH3111 mutation causes the substitution of Gly for Glu at aa position 149 of Orf144b. Survival measurements of a revertant KH3112 which was produced by transforming with DNA containing a part of the orf144b gene of KD8301 showed that the resistances to MC, UV and γ-ray in the revertant were fully restored at a level equal to the wild type. Thus, the orf144b gene required for the multiple-DNA-damaging agent resistance of Dr was designated with the name of pprA (Pleiotropic gene promoting DNA repair). This new gene can express in E. coli at very high level, and make the host E. coli resistant to MC, UV and γ-ray. The pprA gene does not express in normal Dr, but it can be induced to express by treatment with MC, UV and γ-ray. It was thought that the PprA polypeptide is a cytoplasmic protein because of the absence of characteristics found in the aa sequence of membrane proteins

  18. USP1 targeting impedes GBM growth by inhibiting stem cell maintenance and radioresistance.

    Science.gov (United States)

    Lee, Jin-Ku; Chang, Nakho; Yoon, Yeup; Yang, Heekyoung; Cho, Heejin; Kim, Eunhee; Shin, Yongjae; Kang, Wonyoung; Oh, Young Taek; Mun, Gyeong In; Joo, Kyeung Min; Nam, Do-Hyun; Lee, Jeongwu

    2016-01-01

    Clinical benefits from standard therapies against glioblastoma (GBM) are limited in part due to intrinsic radio- and chemoresistance of GBM and inefficient targeting of GBM stem-like cells (GSCs). Novel therapeutic approaches that overcome treatment resistance and diminish stem-like properties of GBM are needed. We determined the expression levels of ubiquitination-specific proteases (USPs) by transcriptome analysis and found that USP1 is highly expressed in GBM. Using the patient GBM-derived primary tumor cells, we inhibited USP1 by shRNA-mediated knockdown or its specific inhibitor pimozide and evaluated the effects on stem cell marker expression, proliferation, and clonogenic growth of tumor cells. USP1 was highly expressed in gliomas relative to normal brain tissues and more preferentially in GSC enrichment marker (CD133 or CD15) positive cells. USP1 positively regulated the protein stability of the ID1 and CHEK1, critical regulators of DNA damage response and stem cell maintenance. Targeting USP1 by RNA interference or treatment with a chemical USP1 inhibitor attenuated clonogenic growth and survival of GSCs and enhanced radiosensitivity of GBM cells. Finally, USP1 inhibition alone or in combination with radiation significantly prolonged the survival of tumor-bearing mice. USP1-mediated protein stabilization promotes GSC maintenance and treatment resistance, thereby providing a rationale for USP1 inhibition as a potential therapeutic approach against GBM. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  19. Determining

    Directory of Open Access Journals (Sweden)

    Bahram Andarzian

    2015-06-01

    Full Text Available Wheat production in the south of Khuzestan, Iran is constrained by heat stress for late sowing dates. For optimization of yield, sowing at the appropriate time to fit the cultivar maturity length and growing season is critical. Crop models could be used to determine optimum sowing window for a locality. The objectives of this study were to evaluate the Cropping System Model (CSM-CERES-Wheat for its ability to simulate growth, development, grain yield of wheat in the tropical regions of Iran, and to study the impact of different sowing dates on wheat performance. The genetic coefficients of cultivar Chamran were calibrated for the CSM-CERES-Wheat model and crop model performance was evaluated with experimental data. Wheat cultivar Chamran was sown on different dates, ranging from 5 November to 9 January during 5 years of field experiments that were conducted in the Khuzestan province, Iran, under full and deficit irrigation conditions. The model was run for 8 sowing dates starting on 25 October and repeated every 10 days until 5 January using long-term historical weather data from the Ahvaz, Behbehan, Dezful and Izeh locations. The seasonal analysis program of DSSAT was used to determine the optimum sowing window for different locations as well. Evaluation with the experimental data showed that performance of the model was reasonable as indicated by fairly accurate simulation of crop phenology, biomass accumulation and grain yield against measured data. The normalized RMSE were 3%, 2%, 11.8%, and 3.4% for anthesis date, maturity date, grain yield and biomass, respectively. Optimum sowing window was different among locations. It was opened and closed on 5 November and 5 December for Ahvaz; 5 November and 15 December for Behbehan and Dezful;and 1 November and 15 December for Izeh, respectively. CERES-Wheat model could be used as a tool to evaluate the effect of sowing date on wheat performance in Khuzestan conditions. Further model evaluations

  20. CREB mediates ICAM-3: inducing radio-resistance, cell growth and migration/invasion of the human nonsmall cell lung cancer cell

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jong Kuk; So, Kwang Sup; Bae, In Hwa; Um, Hong Duck [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2009-05-15

    The ICAM family proteins comprises cell surface molecules that are homologous to NCAM and are members of the single passed type 1 immunoglobulin superfamily (IgSF) that are anchored at the cellular membrane. The ICAM family consists of five subfamilies (ICAM-1 to ICAM-5) of heavily glycosylated cell surface receptors with common functional or structural homology. The extracellular domains of ICAM protein have roles in immune response and inflammation through various cell-cell interactions. The cytoplasmic tail residues of ICAM-3 participate in intracellular signaling such as calcium mobilization and tyrosine phosphorylation. Interestingly, the ICAM proteins appear to have a dual role in cancer. ICAM molecules may target and block tumor progression by stimulation of an immune response such as leukocyte activation. Conversely, other investigations have shown that ICAM molecules are involved in cancer malignancy because their increased expressions are associated with a poor diagnosis, lower survival rates and invasion in several cancers including melanoma, breast cancer and leukemia. We have also reported that an increase of ICAM-3 expression in several cancer cells and specimens of cervical cancer patient induce enhanced radio-resistance by the activation of focal adhesion kinase (FAK) and promote cancer cell proliferation by the activation of Akt and p44/42 MAPK. Therefore, these previous reports imply that ICAM-3 has various undefined roles in cancer. In this study, we investigated whether ICAM-3 increase cell migration and invasion through CREB activation and CREB has a role of increase of radioresistance and cell growth.

  1. Radioresistance of inorganic glasses

    International Nuclear Information System (INIS)

    Vorob'ev, A.A.; Zavadovskaya, E.K.; Fedorov, B.V.; Starodubtsev, V.A.

    1977-01-01

    Regularities are considered in the variation of properties of glass due to irradiations. On the basis of previous theoretical statements and experimental investigations, it is inferred that the irradiation resistance of glasses of the same type, synthesis conditions, content of impurities and amount of imperfections, is a function of the ''element-oxygen'' bond energy. The irradiation resistance depends on the number and the nature of glass structure imperfections. The averaged level of bonding forces is indicative of the glass formation temperature; the imperfections in glasses are formed in structure elements whose amount predominates as compared to the others. Electric charges which accumulate on the crack surface tend to increase its size, thus lessening even further the electric strength of the dielectric. The greater the irradiation time, the greater the number of irradiation imperfections causing a drop in the electric strength of glass. When choosing a glass for service in a radiation field, it is necessary to select those of a highest temperature of glass formation and with a least amount of imperfections

  2. Centromere replication timing determines different forms of genomic instability in Saccharomyces cerevisiae checkpoint mutants during replication stress.

    Science.gov (United States)

    Feng, Wenyi; Bachant, Jeff; Collingwood, David; Raghuraman, M K; Brewer, Bonita J

    2009-12-01

    Yeast replication checkpoint mutants lose viability following transient exposure to hydroxyurea, a replication-impeding drug. In an effort to understand the basis for this lethality, we discovered that different events are responsible for inviability in checkpoint-deficient cells harboring mutations in the mec1 and rad53 genes. By monitoring genomewide replication dynamics of cells exposed to hydroxyurea, we show that cells with a checkpoint deficient allele of RAD53, rad53K227A, fail to duplicate centromeres. Following removal of the drug, however, rad53K227A cells recover substantial DNA replication, including replication through centromeres. Despite this recovery, the rad53K227A mutant fails to achieve biorientation of sister centromeres during recovery from hydroxyurea, leading to secondary activation of the spindle assembly checkpoint (SAC), aneuploidy, and lethal chromosome segregation errors. We demonstrate that cell lethality from this segregation defect could be partially remedied by reinforcing bipolar attachment. In contrast, cells with the mec1-1 sml1-1 mutations suffer from severely impaired replication resumption upon removal of hydroxyurea. mec1-1 sml1-1 cells can, however, duplicate at least some of their centromeres and achieve bipolar attachment, leading to abortive segregation and fragmentation of incompletely replicated chromosomes. Our results highlight the importance of replicating yeast centromeres early and reveal different mechanisms of cell death due to differences in replication fork progression.

  3. The effect of radiosensitizers on the survival response of hypoxic mammalian cells: The low X-ray dose region, hypersensitivity and induced radioresistance

    International Nuclear Information System (INIS)

    Skov, K.A.; MacPhail, H.S.; Marples, B.

    1994-01-01

    It has been shown previously that the extent of chemical modification of the hypoxic radiation response is dependent on dose. Some types of sensitizer are more effective at low doses (to 4 Gy) than at higher doses. Since such drugs are possible adjuvants to radiotherapy, the mechanisms responsible for the variable response at clinical doses are summarized, and the effects of cisplatin and buthionine sulfoximine on the purported induced response to radiation in hypoxic cells are presented. Cisplatin at a low, nontoxic concentration (1 μM) appears to abolish the increased radioresistant portion of the survival response. A role for high-mobility-group protein binding by platinum drugs is hypothesized to explain their interaction with radiation, and conversely, it is suggested that the heretofore unexplained different behavior of certain hypoxic sensitizers at low doses could be, at least in part, an effect on the induction of resistance. 36 refs., 2 figs

  4. TGF-β and Hypoxia/Reoxygenation Promote Radioresistance of A549 Lung Cancer Cells through Activation of Nrf2 and EGFR

    Directory of Open Access Journals (Sweden)

    Sae-lo-oom Lee

    2016-01-01

    Full Text Available Although many studies have examined the roles of hypoxia and transforming growth factor- (TGF- β separately in the tumor microenvironment, the effects of simultaneous treatment with hypoxia/reoxygenation and TGF-β on tumor malignancy are unclear. Here, we investigated the effects of redox signaling and oncogenes on cell proliferation and radioresistance in A549 human lung cancer cells in the presence of TGF-β under hypoxia/reoxygenation conditions. Combined treatment with TGF-β and hypoxia activated epidermal growth factor receptor (EGFR and nuclear factor (erythroid-derived 2-like 2 (Nrf2, a redox-sensitive transcription factor. Interestingly, Nrf2 knockdown suppressed the effects of combined treatment on EGFR phosphorylation. In addition, blockade of EGFR signaling also suppressed induction of Nrf2 following combined treatment with hypoxia and TGF-β, indicating that the combined treatment induced positive crosstalk between Nrf2 and EGFR. TGF-β and hypoxia/reoxygenation increased the accumulation of reactive oxygen species (ROS, while treatment with N-acetyl-L-cysteine abolished the activation of Nrf2 and EGFR. Treatment with TGF-β under hypoxic conditions increased the proliferation of A549 cells compared with that after vehicle treatment. Moreover, cells treated with the combined treatment exhibited resistance to ionizing radiation (IR, and knockdown of Nrf2 increased IR-induced cell death under these conditions. Thus, taken together, our findings suggested that TGF-β and hypoxia/reoxygenation promoted tumor progression and radioresistance of A549 cells through ROS-mediated activation of Nrf2 and EGFR.

  5. Daoy medulloblastoma cells that express CD133 are radioresistant relative to CD133- cells, and the CD133+ sector is enlarged by hypoxia

    International Nuclear Information System (INIS)

    Blazek, Ed R.; Foutch, Jennifer L.; Maki, Guitta

    2007-01-01

    Purpose: Primary medulloblastoma and glioblastoma multiforme tumor cells that express the surface marker CD133 are believed to be enriched for brain tumor stem cells because of their unique ability to initiate or reconstitute tumors in immunodeficient mice. This study sought to characterize the radiobiological properties and marker expression changes of CD133+ vs. CD133- cells of an established medulloblastoma cell line. Methods and Materials: Daoy and D283 Med cell lines were stained with fluorescently labeled anti-CD133 antibody and sorted into CD133+ and CD133- populations. The effect of oxygen (2% vs. 20%) on CD133 expression was measured. Both populations were analyzed for marker stability, cell cycle distribution, and radiosensitivity. Results: CD133+ Daoy cells restored nearly native CD133+ and CD133- populations within 18 days, whereas CD133- cells remained overwhelmingly CD133-. Culturing Daoy cells in 2% oxygen rather than the standard 20% oxygen increased their CD133 expression 1.6-fold. CD133+ Daoy cells were radioresistant via the β-parameter of the linear-quadratic model relative to CD133- Daoy cells, although their α-parameters and cell cycle distributions were identical. Conclusions: Restoration of the original CD133+ and CD133- populations from CD133+ Daoy cells in serum is further evidence that CD133+ cells are functionally distinct from CD133- cells. The radioresistance of CD133+ compared with CD133- Daoy cells is consistent with better repair of sublethal damage. Enlargement of the CD133+ sector is a new feature of the hypoxic response

  6. Radio-resistance of some bacterial pathogens in soft-shell clams (Mya arenaria) and mussels (Mytilus edulis)

    International Nuclear Information System (INIS)

    Licciardello, J.J.; D'Entremont, D.L.; Lundstrom, R.C.

    1989-01-01

    Gamma-irradiation decimal reduction doses were determined for E. coli, Salmonella typhimurium, Shigella flexneri, Strept. faecalis, Staph, aureus, and the Total Plate Count in a soft-shell clam or mussel substrate. Factors to be considered for designing and irradiation bacterial-decontamination process for shellfish are discussed

  7. Extracting the normal lung dose–response curve from clinical DVH data: a possible role for low dose hyper-radiosensitivity, increased radioresistance

    International Nuclear Information System (INIS)

    Gordon, J J; Snyder, K; Zhong, H; Barton, K; Sun, Z; Chetty, I J; Matuszak, M; Ten Haken, R K

    2015-01-01

    In conventionally fractionated radiation therapy for lung cancer, radiation pneumonitis’ (RP) dependence on the normal lung dose-volume histogram (DVH) is not well understood. Complication models alternatively make RP a function of a summary statistic, such as mean lung dose (MLD). This work searches over damage profiles, which quantify sub-volume damage as a function of dose. Profiles that achieve best RP predictive accuracy on a clinical dataset are hypothesized to approximate DVH dependence.Step function damage rate profiles R(D) are generated, having discrete steps at several dose points. A range of profiles is sampled by varying the step heights and dose point locations. Normal lung damage is the integral of R(D) with the cumulative DVH. Each profile is used in conjunction with a damage cutoff to predict grade 2 plus (G2+) RP for DVHs from a University of Michigan clinical trial dataset consisting of 89 CFRT patients, of which 17 were diagnosed with G2+ RP.Optimal profiles achieve a modest increase in predictive accuracy—erroneous RP predictions are reduced from 11 (using MLD) to 8. A novel result is that optimal profiles have a similar distinctive shape: enhanced damage contribution from low doses (<20 Gy), a flat contribution from doses in the range ∼20–40 Gy, then a further enhanced contribution from doses above 40 Gy. These features resemble the hyper-radiosensitivity / increased radioresistance (HRS/IRR) observed in some cell survival curves, which can be modeled using Joiner’s induced repair model.A novel search strategy is employed, which has the potential to estimate RP dependence on the normal lung DVH. When applied to a clinical dataset, identified profiles share a characteristic shape, which resembles HRS/IRR. This suggests that normal lung may have enhanced sensitivity to low doses, and that this sensitivity can affect RP risk. (paper)

  8. Cell adhesion-mediated radioresistance (CAM-RR). Extracellular matrix-dependent improvement of cell survival in human tumor and normal cells in vitro

    International Nuclear Information System (INIS)

    Cordes, N.; Meineke, V.

    2003-01-01

    Background: Cell-extracellular matrix (ECM) contact is thought to have great impact on cellular mechanisms resulting in increased cell survival upon exposure to ionizing radiation. Several human tumor cell lines and normal human fibroblastic cell strains of different origin, all of them expressing the wide-spread and important integrin subunit β1, were irradiated, and clonogenic cell survival, β1-integrin cell surface expression, and adhesive functionality were investigated. Material and Methods: Human tumor cell lines A172 (glioblastoma), PATU8902 (pancreas carcinoma), SKMES1 (lung carcinoma), A549 (lung carcinoma), and IPC298 (melanoma) as well as normal human skin (HSF1) and lung fibroblasts (CCD32) and human keratinocytes (HaCaT) were irradiated with 0-8 Gy. Besides colony formation assays, β1-integrin cell surface expression by flow cytometry and adhesive functionality by adhesion assays were analyzed. Results: All cell lines showed improved clonogenic survival after irradiation in the presence of fibronectin as compared to plastic. Irradiated cells exhibited a significant, dose-dependent increase in β1-integrin cell surface expression following irradiation. As a parameter of the adhesive functionality of the β1-integrin, a radiation-dependent elevation of cell adhesion to fibronectin in comparison with adhesion to plastic was demonstrated. Conclusion: The in vitro cellular radiosensitivity is highly influenced by fibronectin according to the phenomenon of cell adhesion-mediated radioresistance. Additionally, our emerging data question the results of former and current in vitro cytotoxicity studies performed in the absence of an ECM. These findings might also be important for the understanding of malignant transformation, anchorage-independent cell growth, optimization of radiotherapeutic regimes and the prevention of normal tissue side effects on the basis of experimental radiobiological data. (orig.)

  9. Genomic amplification of Fanconi anemia complementation group A (FancA) in head and neck squamous cell carcinoma (HNSCC): Cellular mechanisms of radioresistance and clinical relevance.

    Science.gov (United States)

    Hess, Julia; Unger, Kristian; Orth, Michael; Schötz, Ulrike; Schüttrumpf, Lars; Zangen, Verena; Gimenez-Aznar, Igor; Michna, Agata; Schneider, Ludmila; Stamp, Ramona; Selmansberger, Martin; Braselmann, Herbert; Hieber, Ludwig; Drexler, Guido A; Kuger, Sebastian; Klein, Diana; Jendrossek, Verena; Friedl, Anna A; Belka, Claus; Zitzelsberger, Horst; Lauber, Kirsten

    2017-02-01

    Radio (chemo) therapy is a crucial treatment modality for head and neck squamous cell carcinoma (HNSCC), but relapse is frequent, and the underlying mechanisms remain largely elusive. Therefore, novel biomarkers are urgently needed. Previously, we identified gains on 16q23-24 to be associated with amplification of the Fanconi anemia A (FancA) gene and to correlate with reduced progression-free survival after radiotherapy. Here, we analyzed the effects of FancA on radiation sensitivity in vitro, characterized the underlying mechanisms, and evaluated their clinical relevance. Silencing of FancA expression in HNSCC cell lines with genomic gains on 16q23-24 resulted in significantly impaired clonogenic survival upon irradiation. Conversely, overexpression of FancA in immortalized keratinocytes conferred increased survival accompanied by improved DNA repair, reduced accumulation of chromosomal translocations, but no hyperactivation of the FA/BRCA-pathway. Downregulation of interferon signaling as identified by microarray analyses, enforced irradiation-induced senescence, and elevated production of the senescence-associated secretory phenotype (SASP) appeared to be candidate mechanisms contributing to FancA-mediated radioresistance. Data of the TCGA HNSCC cohort confirmed the association of gains on 16q24.3 with FancA overexpression and impaired overall survival. Importantly, transcriptomic alterations similar to those observed upon FancA overexpression in vitro strengthened the clinical relevance. Overall, FancA amplification and overexpression appear to be crucial for radiotherapeutic failure in HNSCC. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. The role of Rad 51 protein in radioresistance of spheroid model of Du 145 prostate carcinoma cell line

    International Nuclear Information System (INIS)

    Taghizadeh, M.; Khoei, S.; Nikoofar, A. R.; Ghamsari, L.; Goliaei, B.

    2009-01-01

    Rad 51 is a protein with critical role in double strand break repair. Down-regulation of this protein has a significant effect in radiosensitivity of some cell lines like prostate carcinoma. Compared to monolayer cell culture model, the spheroids are more resistant to radiation. The aim of the current study was to determine the Rad 51 protein level in Du 145 spheroids, and monolayer cells before and after exposure to gamma irradiation. Materials and Methods: In the present study, western blot was used to determine the level of Rad 51 protein in Du 145 cell line grown as monolayer and spheroid. Results: Western blot analysis showed that in the spheroid cells, Rad 51 had an elevated level before and after radiation in comparison with monolayer cells. Higher doses of radiation induced elevated expression of Rad 51 protein in both culture models.The level of at protein after exposure to gamma rays had been time-dependent. Conclusion: Rad 51 might act as a mediator of radiation resistance in tumor cells. Repression of Rad 51 activity could be a prominent strategy to overcome radiation resistance of tumors.

  11. Radioresistant Spodoptera frugiperda 9 insect cells display excessive resistance to 'endoplasmic reticulum' stress and calcium disturbances via pre-emptive activation of unfolded protein response pathway

    International Nuclear Information System (INIS)

    Guleria, Ayushi; Chandna, Sudhir

    2016-01-01

    Endoplasmic Reticulum (ER) performs multiple cellular functions such as proper folding of newly synthesized proteins and calcium homeostasis. ER stress triggers unfolded protein response (UPR) that attempts to restore normal ER function and resists damage-induced cell death. Lepidopteran Sf9 insect cells (derived from Spodoptera frugiperda) display 100-200 times higher radioresistance than mammalian cells. We have earlier reported that gamma-radiation doses <1000 Gy fail to trigger increase in cytosolic calcium in Sf9 cells, indicating resilience to calcium/ ER disturbances

  12. Altered Cross-Linking of HSP27 by Zerumbone as a Novel Strategy for Overcoming HSP27-Mediated Radioresistance

    International Nuclear Information System (INIS)

    Choi, Seo-Hyun; Lee, Yoon-Jin; Seo, Woo Duck; Lee, Hae-June; Nam, Joo-Won; Lee, Yoo Jin; Kim, Joon; Seo, Eun-Kyoung; Lee, Yun-Sil

    2011-01-01

    Purpose: HSP27 or HSP25 negatively regulates apoptosis pathways after radiation or chemotherapeutic agents. Abrogation of HSP27 function may be a candidate target for overcoming radio- and chemoresistance. Methods and Materials: Zerumbone (ZER), a cytotoxic component isolated from Zingiber zerumbet smith. Clonogenic survival assay and flow cytometry after Annexin V staining were performed to determine in vitro sensitization effects of ZER with ionizing radiation. A nude mouse xenografting system was also applied to detect in vivo radiosensitizing effects of ZER. Results: ZER produced cross-linking of HSP27, which was dependent on inhibition of the monomeric form of HSP27. ZER was directly inserted between the disulfide bond in the HSP27 dimer and modified normal HSP27 dimerization. Pretreatment with ZER before radiation inhibited the binding affinity between HSP27 and apoptotic molecules, such as cytochrome c and PKCδ, and induced sensitization in vitro and in an in vivo xenografted nude mouse system. Structural analogs lacking only the carbonyl group in ZER, such as α-humulene (HUM) and 8-hydroxy-humulen (8-OH-HUM), did not affect normal cross-linking of HSP27 and did not induce radiosensitization. Conclusions: We suggest that altered cross-linking of HSP27 by ZER is a good strategy for abolishing HSP27-mediated resistance.

  13. Single Strand Annealing Plays a Major Role in RecA-Independent Recombination between Repeated Sequences in the Radioresistant Deinococcus radiodurans Bacterium.

    Directory of Open Access Journals (Sweden)

    Solenne Ithurbide

    2015-10-01

    Full Text Available The bacterium Deinococcus radiodurans is one of the most radioresistant organisms known. It is able to reconstruct a functional genome from hundreds of radiation-induced chromosomal fragments. Our work aims to highlight the genes involved in recombination between 438 bp direct repeats separated by intervening sequences of various lengths ranging from 1,479 bp to 10,500 bp to restore a functional tetA gene in the presence or absence of radiation-induced DNA double strand breaks. The frequency of spontaneous deletion events between the chromosomal direct repeats were the same in recA+ and in ΔrecA, ΔrecF, and ΔrecO bacteria, whereas recombination between chromosomal and plasmid DNA was shown to be strictly dependent on the RecA and RecF proteins. The presence of mutations in one of the repeated sequence reduced, in a MutS-dependent manner, the frequency of the deletion events. The distance between the repeats did not influence the frequencies of deletion events in recA+ as well in ΔrecA bacteria. The absence of the UvrD protein stimulated the recombination between the direct repeats whereas the absence of the DdrB protein, previously shown to be involved in DNA double strand break repair through a single strand annealing (SSA pathway, strongly reduces the frequency of RecA- (and RecO- independent deletions events. The absence of the DdrB protein also increased the lethal sectoring of cells devoid of RecA or RecO protein. γ-irradiation of recA+ cells increased about 10-fold the frequencies of the deletion events, but at a lesser extend in cells devoid of the DdrB protein. Altogether, our results suggest a major role of single strand annealing in DNA repeat deletion events in bacteria devoid of the RecA protein, and also in recA+ bacteria exposed to ionizing radiation.

  14. Cell death induced by ionizing radiations in human radio-resistant tumours: in-vitro and in-vivo study of mechanisms involved in its induction by different types of radiations and pharmacological modulation

    International Nuclear Information System (INIS)

    Altmeyer, Anais

    2010-01-01

    Whereas chemo-radiotherapy protocols revealed to be very efficient when taking tumours into care, the treatment of some tumours remains very limited due to their critical location or to the weak radio-sensitivity to conventional radiations. One way to work around this problem is to use high linear energy transfer radiations or hadron therapy, in combination with radio-sensitizers. This research thesis reports the assessment of radio-sensitizer effects of different molecules on human radio-resistant cell lines and more particularly the SK-Hep1 line from a hepatocellular carcinoma. In vitro studies have been performed and then in vivo studies by using fast neutron irradiation on a mice liver sample. Observations made by optic fibre confocal microscopy and transmission electronic microscopy confirmed in vitro observations: the prevailing cell death after such an irradiation is the autophagic cell death. It shows the importance of the autophagic phenomenon induced by radiations with high linear transfer energy. This could lead to new therapeutic protocols for radio-resistant cancers [fr

  15. Double-negative feedback loop between long non-coding RNA TUG1 and miR-145 promotes epithelial to mesenchymal transition and radioresistance in human bladder cancer cells.

    Science.gov (United States)

    Tan, Jiemei; Qiu, Kaifeng; Li, Mingyi; Liang, Ying

    2015-10-07

    LncRNAs have a critical role in the regulation of cellular processes such as cancer progression and metastasis. In the present study, we confirmed that TUG1 was overexpressed in bladder cancer tissues and established cell lines. Knockdown of TUG1 inhibited bladder cancer cell metastasis both in vitro and in vivo. Furthermore, we found that TUG1 promoted cancer cell invasion and radioresistance through inducing epithelial-to-mesenchymal transition (EMT). Interestingly, TUG1 decreased the expression of miR-145 and there was a reciprocal repression between TUG1 and miR-145 in an Argonaute2-dependent manner. ZEB2 was identified as a down-stream target of miR-145 and TUG1 exerted its function through the miR-145/ZEB2 axis. In summary, our data indicated that blocking TUG1 function may be an effective anti-cancer therapy. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  16. MiR-146b-5p overexpression attenuates stemness and radioresistance of glioma stem cells by targeting HuR/lincRNA-p21/β-catenin pathway

    Science.gov (United States)

    Yang, Wei; Yu, Hongquan; Shen, Yueming; Liu, Yingying; Yang, Zhanshan; Sun, Ting

    2016-01-01

    A stem-like subpopulation existed in GBM cells, called glioma stem cells (GSCs), might contribute to cancer invasion, angiogenesis, immune evasion, and therapeutic resistance, providing a rationale to eliminate GSCs population and their supporting niche for successful GBM treatment. LincRNA-p21, a novel regulator of cell proliferation, apoptosis and DNA damage response, is found to be downregulated in several types of tumor. However, little is known about the role of lincRNA-p21 in stemness and radioresistance of GSCs and its regulating mechanisms. In this study, we found that lincRNA-p21 negatively regulated the expression and activity of β-catenin in GSCs. Downregulation of lincRNA-p21 in GSCs was resulted from upregulation of Hu antigen R (HuR) expression caused by miR-146b-5p downregulation. MiR-146b-5p overexpression increased apoptosis and radiosensitivity, decreased cell viability, neurosphere formation capacity and stem cell marker expression, and induced differentiation in GSCs. Moreover, knock-down lincRNA-p21 or HuR and β-catenin overexpression could rescue the phenotypic changes resulted from miR-146b-5p overexpression in GSCs. These findings suggest that targeting the miR-146b-5p/HuR/lincRNA-p21/β-catenin signaling pathway may be valuable therapeutic strategies against glioma. PMID:27166258

  17. Analysis of the factors in determining radiosensitivity in mammalian cells by using radio-sensitive and -resistant clones isolated from HeLa S3 cells in vitro

    International Nuclear Information System (INIS)

    Nikaido, Osamu; Horikawa, Masakatsu

    1976-01-01

    The factors in determining radiosensitivity of cultured mammalian cells were analysed by using two clones each having different radiosensitivities. The radiosensitive clones were isolated from HeLa S3 cells by the N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-treatment, X-irradiation (200 R) and 5-bromodeoxyuridine (BUdR)-visible light method. On the other hand, the radioresistant clone was isolated by single X-irradiation (2000 R) from MNNG-treated HeLa S3 cell population. The radiosensitivities expressed in D sub(o) and D sub(q) values were 110 and 140 R in radiosensitive SM-1a clone and 180 and 230 R in radioresistant RM-1b clone respectively. The biological and biochemical characteristics of both clones such as the distribution of chromosome numbers, formation and rejoining of single strand breaks in DNA caused by X-irradiation, non-protein sulfhydryl (NPSH) and apparent total sulfhydryl (APSH) contents were measured. Among the characteristics analysed, different contents of NPSH in the cell were well correlated to their daiosensitivities among the original HeLa S3 cells, SM-1a and RM-1b clone. Additionally, it was found that the radioresistant L.P3 Co-3 cells isolated by Tsuboi et al. from the original mouse L.P3 cells by means of serial irradiation with 60 Co γ-rays have more abundant NPSH than the original L.P3 cells. From these results, it can be concluded that the amount of NPSH play the main role in determining radiosensitivity in cultured mammalian cells. (auth.)

  18. Study of biological effects of varying mixtures of Cf-252 and gamma radiation on the acute radiation syndromes: Relevance to clinical radiotherapy of radioresistant cancer

    International Nuclear Information System (INIS)

    Maruyama, Y.; Wierzbicki, J.; Feola, J.M.

    1993-01-01

    Data for the 30 day bone marrow syndrome (BM-50) and the 6-10 day gastrointestinal (GI-50) syndrome for a one and two fraction schedule and acute and low dose rate irradiation using pure and mixed Cf-252 and photon radiation are presented. The radiation of Cf-252 is a mixture of neutrons and gamma rays. Balb/c mice of both sexes were total body irradiated with acute Co-60, low dose rate Cs-137 and Cf-252 using a 1 x and 2 x schedule. For low linear energy transfer radiations of Co-60 or Cs-137 there was expected to be an increase in the dose to produce the gastrointestinal and bone marrow syndromes with minimal change for Cf-252 neutrons. The proportion of photons in the Cf-252 radiation field were further altered by mixing Cs-137 with the Cf-252 sources and mice were total body irradiated with different proportions of photons to determine the effect on the radiation syndromes. The effects of mixing Cf-252 neutrons with different proportions of photons on the syndromes was determined. There was increase in BM-50 and GI-50 doses with fractionated or low dose rate photon irradiations and the dose modifying factors were 1.3-1.4 for the GI syndrome and 1.2 for the bone marrow syndrome. For Cf-252 there was minimal fractionation effect for the GI-50 syndrome, which increased by 1.1 for x 1 vs. x 2 fractions; for the BM-50 syndrome it rose by a 1.1 factor. For LDR Cs-137 the dose for the GI-50 syndrome rose 2.2-fold. For mixed neutron-photon radiation of 0%, 15%, 35%, and 65% η/γ mixtures, the dose to produce the BM-50 and GI-50 endpoints dropped sharply from 0 to 35% neutrons and remained flat thereafter. For major tissues such as the bone marrow and GI tract, Cf-252 behaved as high linear energy transfer for mixtures of neutrons and gamma rays when the radiations were delivered simultaneously at the low dose rates studied. 35 refs., 3 figs., 2 tabs

  19. Bcl-w, a Radio-resistant Protein, Promotes the Gastric Cancer Cell Migration by inducing the phosphorylation of Focal Adhesion Kinase

    International Nuclear Information System (INIS)

    Bae, In Hwa; Yoon, Sung Hwan; Um, Hong Duck

    2008-01-01

    Gastric cancer is one of the leading malignancies in many countries and lethal for the high incidence of recurrence even after drastic surgical resection. Because local invasion and subsequent metastasis contributes to the failure of anticancer treatments of gastric cancer, a better understanding of the mechanisms involved in tumor invasiveness within the stomach seems to be essential for the control of this disease. Bcl-w is a prosurvival member of the Bcl-2 protein family, and thus protects cells from γ-irradiation. Recent reports suggest that Bcl-w can be upregulated in gastric cancer cells in a manner associated with the infiltrative (diffuse) types of the tumor. An analysis of Bcl-w function consistently revealed that Bcl-w can also promote the migratory and invasive potentials of gastric cancer cells. While it was shown that Bcl-w increases the invasiveness of cancer cells by sequentially inducing PI3K, Akt, SP1, and MMP-2, cellular components involved in Bcl-w-induced cell migration remain to be determined. This was the reason why we undertook the present study, which shows that FAK is a critical mediator of the cell migration induced by Bcl-w

  20. Study of multidrug resistance and radioresistance

    International Nuclear Information System (INIS)

    Kang, Yoon Koo; Yoo, Young Do

    1999-04-01

    We investigated the mechanism of 5-FU, adriamycin, radiation resistance in Korean gastric cancer cells. First we investigated the relation between Rb and multidrug resistance. Rb stable transfectants exhibited 5- to 10- fold more resistance to adriamycin than the control cells. These Rb transfectants showed increased MDR1 expression. We also investigated up-regulation in radiation-resistant tumor tissues. HSP27, MRP-8, GST, and NKEF-B were up-regulated in radiation resistant tumor. Expression of NKEF-B was also increased by radiation exposure in Head and Neck cells. These results demonstrated that NKEF-B is a stress response protein and it may have an important role in radiation resistance

  1. The clinicopathological factors that determine a local recurrence of rectal cancers that have been treated with surgery and chemoradiotherapy

    International Nuclear Information System (INIS)

    Choi, Chul Won; Kim, Mi Sook; Kim, Min Suk

    2006-01-01

    To evaluate the pathological prognostic factors related to local recurrence after radical surgery and adjuvant radiation therapy in advanced rectal cancer. Fifty-four patients with advanced rectal cancer who were treated with radiation surgery followed by adjuvant radiotherapy and chemotherapy between February 1993 and December 2001 were enrolled in this study. Among these patients, 14 patients experienced local recurrence. Tissue specimens of the patient were obtained to determine pathologic parameters such as histological grade, depth of invasion, venous invasion, lymphatic invasion, neural invasion and immuno histopathological analysis for expression of p53, Ki-67 c-erb, ezrin, c-met, phosphorylated S6 kinase, S100A4, and HIF-1 alpha. The correlation of these parameters with the tumor response to radiotherapy was statistically analyzed using the chi-square test, multivariate analysis, and the hierarchical clustering method. In univariate analysis, the histological tumor grade, venous invasion, invasion depth of the tumor and the over expression of c-met and HIF-1 alpha were accompanied with radioresistance that was found to be statistically significant. In multivariate analysis, venous invasion, invasion depth of tumor and over expression of c-met were also accompanied with radioresistance that was found to be statistically significant. By analysis with hierarchical clustering, the invasion depth of the tumor, and the over expression of c-met and HIF-1 alpha were factors found to be related to local recurrence. Whereas 71.4% of patients with local recurrence had 2 or more these factors, only 27.5% of patients without local recurrence had 2 or more of these factors. In advanced rectal cancer patients treated by radical surgery and adjuvant chemo-radiation therapy, the poor prognostic factors found to be related to local recurrence were HIF-1 alpha positive, c-met positive, and an invasion depth more than 5.5 mm. A prospective study is necessary to confirm whether

  2. Hepatocytes Determine the Hypoxic Microenvironment and Radiosensitivity of Colorectal Cancer Cells Through Production of Nitric Oxide That Targets Mitochondrial Respiration

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Heng; Verovski, Valeri N.; Leonard, Wim; Law, Ka Lun; Vermeersch, Marieke; Storme, Guy; Van den Berge, Dirk; Gevaert, Thierry; Sermeus, Alexandra [Department of Radiotherapy, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels (Belgium); De Ridder, Mark, E-mail: mark.deridder@uzbrussel.be [Department of Radiotherapy, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels (Belgium)

    2013-03-01

    Purpose: To determine whether host hepatocytes may reverse hypoxic radioresistance through nitric oxide (NO)-induced oxygen sparing, in a model relevant to colorectal cancer (CRC) liver metastases. Methods and Materials: Hepatocytes and a panel of CRC cells were incubated in a tissue-mimetic coculture system with diffusion-limited oxygenation, and oxygen levels were monitored by an oxygen-sensing fluorescence probe. To activate endogenous NO production, cocultures were exposed to a cytokine mixture, and the expression of inducible nitric oxide synthase was analyzed by reverse transcription–polymerase chain reaction, Western blotting, and NO/nitrite production. The mitochondrial targets of NO were examined by enzymatic activity. To assess hypoxic radioresponse, cocultures were irradiated and reseeded for colonies. Results: Resting hepatocytes consumed 10-40 times more oxygen than mouse CT26 and human DLD-1, HT29, HCT116, and SW480 CRC cells, and thus seemed to be the major effectors of hypoxic conditioning. As a result, hepatocytes caused uniform radioprotection of tumor cells at a 1:1 ratio. Conversely, NO-producing hepatocytes radiosensitized all CRC cell lines more than 1.5-fold, similar to the effect of selective mitochondrial inhibitors. The radiosensitizing effect was associated with a respiratory self-arrest of hepatocytes at the level of aconitase and complex II, which resulted in profound reoxygenation of tumor cells through oxygen sparing. Nitric oxide–producing hepatocytes were at least 10 times more active than NO-producing macrophages to reverse hypoxia-induced radioresistance. Conclusions: Hepatocytes were the major determinants of the hypoxic microenvironment and radioresponse of CRC cells in our model of metabolic hypoxia. We provide evidence that reoxygenation and radiosensitization of hypoxic CRC cells can be achieved through oxygen sparing induced by endogenous NO production in host hepatocytes.

  3. Hepatocytes Determine the Hypoxic Microenvironment and Radiosensitivity of Colorectal Cancer Cells Through Production of Nitric Oxide That Targets Mitochondrial Respiration

    International Nuclear Information System (INIS)

    Jiang, Heng; Verovski, Valeri N.; Leonard, Wim; Law, Ka Lun; Vermeersch, Marieke; Storme, Guy; Van den Berge, Dirk; Gevaert, Thierry; Sermeus, Alexandra; De Ridder, Mark

    2013-01-01

    Purpose: To determine whether host hepatocytes may reverse hypoxic radioresistance through nitric oxide (NO)-induced oxygen sparing, in a model relevant to colorectal cancer (CRC) liver metastases. Methods and Materials: Hepatocytes and a panel of CRC cells were incubated in a tissue-mimetic coculture system with diffusion-limited oxygenation, and oxygen levels were monitored by an oxygen-sensing fluorescence probe. To activate endogenous NO production, cocultures were exposed to a cytokine mixture, and the expression of inducible nitric oxide synthase was analyzed by reverse transcription–polymerase chain reaction, Western blotting, and NO/nitrite production. The mitochondrial targets of NO were examined by enzymatic activity. To assess hypoxic radioresponse, cocultures were irradiated and reseeded for colonies. Results: Resting hepatocytes consumed 10-40 times more oxygen than mouse CT26 and human DLD-1, HT29, HCT116, and SW480 CRC cells, and thus seemed to be the major effectors of hypoxic conditioning. As a result, hepatocytes caused uniform radioprotection of tumor cells at a 1:1 ratio. Conversely, NO-producing hepatocytes radiosensitized all CRC cell lines more than 1.5-fold, similar to the effect of selective mitochondrial inhibitors. The radiosensitizing effect was associated with a respiratory self-arrest of hepatocytes at the level of aconitase and complex II, which resulted in profound reoxygenation of tumor cells through oxygen sparing. Nitric oxide–producing hepatocytes were at least 10 times more active than NO-producing macrophages to reverse hypoxia-induced radioresistance. Conclusions: Hepatocytes were the major determinants of the hypoxic microenvironment and radioresponse of CRC cells in our model of metabolic hypoxia. We provide evidence that reoxygenation and radiosensitization of hypoxic CRC cells can be achieved through oxygen sparing induced by endogenous NO production in host hepatocytes

  4. Radiation Resistance of Enzymes in Foods Irradiated Against Microbial Damage; Radioresistance des Enzymes dans les Denrees Alimentaires Irradiees pour les Proteger Contre les Alterations Dues a des Bacteries; Radiatsionnaya ustojchivost' ehnzimov v pishchevykh produktakh,obluchennykh protiv vrednogo vozdejstviya mikrobov; Radiorresistencia de las Enzimas en los Alimentos Irradiados

    Energy Technology Data Exchange (ETDEWEB)

    Vas, K. [Joint FAO/IAEA Division of Atomic Energy in Agriculture, International Atomic Energy Agency, Vienna (Austria)

    1966-11-15

    Most enzymes which play a role in the storage, processing and preservation of food are rather resistant to ionizing radiations. Generally speaking, their in situ radio-resistance is about an order of magnitude higher than that of the microorganisms causing spoilage or public health hazards. Thus, radiation doses adequate to microbiological stabilization, and at present considered just feasible economically, are insufficient to prevent enzymatic deterioration. Many attempts have already been made to inactivate enzymes in food by radiation but, judging by the relative failure of most of these efforts, much more background information seems to be necessary to deal with the problem on a more rational basis. To date, work in radiation enzymology has, to a large extent, been carried out in systems of medical interest, generally giving results not readily transposable to food systems. In the past (a) the mechanism of inactivation, as well as the roles of (b) enzyme concentration, (c) water activity of the medium, (d) oxygen concentration, (e) pH and (f) temperature, have been studied most intensively. This is reviewed in the paper. Since, in the majority of the reported experiments, the degree of purity of the enzyme has not been stated (or known, for that matter to the authors themselves), and since, on the other hand, radio-modifying substances are known to exert a decisive influence on the radiation inactivation of enzymes, it is felt that much more work is still needed on radio-protectors and radiation sensitizers in combination with highly-purified enzymes. The usual great radio-sensitivity of high-purity enzymes and the contrasting extreme resistance of enzymes in the tissues and in their unpurified extracts certainly indicate the need for finding the reasons for this difference in order to facilitate possibly a rational approach of controlling enzyme activity in food irradiation. In this way, perhaps some novel ''combination method'' can eventually be developed in

  5. Sex determination

    Indian Academy of Sciences (India)

    The sex-determining system differs considerably among organisms. Even among insect species, the genetic system for sex-determination is highly diversified. In Drosophila melanogaster, somatic sexual differentiation is regulated by a well characterized genetic hierarchy X : A > Sxl > tra/tra2 > dsx and fru. This cascade ...

  6. Risk determination

    International Nuclear Information System (INIS)

    1993-01-01

    The issue gives a survey of the legal, theological, statistical and health aspects of risk determination. It includes the opinions of physicians, epidemiologists, mathematicians, toxicologists, biologists, theologists and physicists who explain and illustrate the term of risk from their perspective. (orig./DG) [de

  7. Comparison of protein patterns of xrs-5, a radiosensitive Chinese hamster ovary cell line, and CHO-K1, its radioresistant parent, using two-dimensional gel-electrophoresis

    International Nuclear Information System (INIS)

    Kramer, J.M.

    1991-01-01

    X-ray sensitive strains of Chinese hamster ovary cell lines have been used to analyze radiation repair mechanisms. One cell line, xrs-5, has been shown to be very sensitive to ionizing radiation and radical forming chemical mutagens. This sensitivity is thought to be a result a mutation in the DNA double strand break (DSB) repair mechanism, and its characterization has been a goal of several repair mechanism studies. Using two-dimensional gel electrophoresis, we have detected a protein (MW approximately 55KD) in the DNA/Nuclear Matrix (nucleoid) cell fraction of CHO-Kl cells that is absent in the nucleoid fraction of xrs-5. This protein is present, however, in both CHO-Kl and xrs-5 whole cell protein maps. To determine whether the 55KD protein is responsible for the radiosensitive and defective DSB repair phenotype of xrs-5 cells, studies are now underway to analyze revertants of xrs-5 that are proficient in DSB repair. Furthermore, an effort to sequence the protein in question is planned. 23 refs., 2 figs

  8. Hypoxia as a biomarker for radioresistant cancer stem cells.

    Science.gov (United States)

    Peitzsch, Claudia; Perrin, Rosalind; Hill, Richard P; Dubrovska, Anna; Kurth, Ina

    2014-08-01

    Tumor initiation, growth and relapse after therapy are thought to be driven by a population of cells with stem cell characteristics, named cancer stem cells (CSC). The regulation of their radiation resistance and their maintenance is poorly understood. CSC are believed to reside preferentially in special microenvironmental niches located within tumor tissues. The features of these niches are of crucial importance for CSC self-renewal, metastatic potential and therapy resistance. One of the characteristics of solid tumors is occurrence of less oxygenated (hypoxic regions), which are believed to serve as so-called hypoxic niches for CSC. The purpose of this review was the critical discussion of the supportive role of hypoxia and hypoxia-related pathways during cancer progression and radiotherapy resistance and the relevance for therapeutic implications in the clinic. It is generally known since decades that hypoxia inside solid tumors impedes chemo- and radiotherapy. However, there is limited evidence to date that targeting hypoxic regions during conventional therapy is effective. Nonetheless improved hypoxia-imaging technologies and image guided individualized hypoxia targeted therapy in conjunction with the development of novel molecular targets may be able to challenge the protective effect on the tumor provided by hypoxia.

  9. Chinese hamster pleiotropic multidrug-resistant cells are not radioresistant

    International Nuclear Information System (INIS)

    Mitchell, J.B.; Gamson, J.; Russo, A.; Friedman, N.; DeGraff, W.; Carmichael, J.; Glatstein, E.

    1988-01-01

    The inherent cellular radiosensitivity of a Chinese hamster ovary pleiotropic cell line that is multidrug resistant (CHRC5) was compared to that of its parental cell line (AuxB1). Radiation survival curve parameters n and D0 were 4.5 and 1.1 Gy, respectively, for the CHRC5 line and 5.0 and 1.2 Gy, respectively, for the parental line. Thus, the inherent radiosensitivity of the two lines was similar even though key intracellular free radical scavenging and detoxifying systems employing glutathione, glutathione transferase, and catalase produced enzyme levels that were 2.0-, 1.9-, and 1.9-fold higher, respectively, in the drug-resistant cell line. Glutathione depletion by buthionine sulfoximine resulted in the same extent of aerobic radiosensitization in both lines (approximately 10%). Incorporation of iododeoxyuridine into cellular DNA sensitized both cell lines to radiation. These studies indicate that pleiotropic drug resistance does not necessarily confer radiation resistance

  10. Unusual radioresistance of nitrogen-fixing cultures of Anabaena ...

    Indian Academy of Sciences (India)

    Prakash

    Atlas R M 2004 Handbook of microbiological media; third edition. (Florida: CRC Press) ... nitrogen-fixation, and nodularin production by two Baltic sea cyanobacteria ... Sharma A 1998 Mycotoxins: risk evaluation and management in radiation ...

  11. DNA double strand break repair in a radioresistant cell line

    International Nuclear Information System (INIS)

    Koval, T.M.; Kazmar, E.R.

    1987-01-01

    TN-368 lepidopteran insect cells are on the order of 100 times more resistant to the lethal effects of ionizing radiation than cultured mammalian cells. DNA double strand breaks (DSB) are believed by many to be the critical molecular lesion leading to cell death. The authors therefore measured the rejoining of DSB in TN-368 and V79 Chinese hamster cells. Cells were irradiated on ice with /sup 137/Cs γ rays at a dose rate of 2.5 Gy/min, incubated for various periods of time, and assayed for DNA DSB using the method of neutral elution. The kinetics of DSB rejoining following a dose of 90.2 Gy are similar for both cell lines. Approximately 80% of the DSB are rejoined in both lines by 1 hr postirradiation. However, no further rejoining occurs in the TN-368 cells through at least 6 hr postirradiation, whereas 90% of the DSB are rejoined in the V79 cells by 2 hr postirradiation. Other studies (from 22.6 to 226 Gy) demonstrate that the amount of rejoining of DSB varies inversely with dose for the V79 cells but remains constant for the TN-368 cells. These findings do not support the hypothesis that unrejoined DNA DSB represent the major lesion resulting in cell death

  12. Role of endogenous substances in enhancing radioresistance background

    International Nuclear Information System (INIS)

    Goncharenko, E.N.; Gorskaya, T.G.; Graevskaya, E.Eh.; Kozlova, M.A.

    1979-01-01

    Presumable sources of endogenous were studied amines in radiosensitive tissues under the effect of radioprotective agents were studied. The data obtained support the idea that mast cells of rats, having large deposits of biogenous amines, might be one of the reserves contributing to mobilization of endogeneous protective resources of the organism treated with radioprotective agents

  13. Review of anticancer and antioxidant activities of radioresistant ...

    African Journals Online (AJOL)

    Prof. Ogunji

    mechanism underlying the tolerance of these organisms to ionizing radiation. ... radiation dose environment, drastic temperature variations and high salinity ... extremophile like Deinococcus radiodurans for instance, is highly dependent on.

  14. Protein function prediction involved on radio-resistant bacteria

    International Nuclear Information System (INIS)

    Mezhoud, Karim; Mankai, Houda; Sghaier, Haitham; Barkallah, Insaf

    2009-01-01

    Previously, we identified 58 proteins under positive selection in ionizing-radiation-resistant bacteria (IRRB) but absent in all ionizing-radiation-sensitive bacteria (IRSB). These are good reasons to believe these 58 proteins with their interactions with other proteins (interactomes) are a part of the answer to the question as to how IRRB resist to radiation, because our knowledge of interactomes of positively selected orphan proteins in IRRB might allow us to define cellular pathways important to ionizing-radiation resistance. Using the Database of Interacting Proteins and the PSIbase, we have predicted interactions of orthologs of the 58 proteins under positive selection in IRRB but absent in all IRSB. We used integrate experimental data sets with molecular interaction networks and protein structure prediction from databases. Among these, 18 proteins with their interactomes were identified in Deinococcus radiodurans R1. DNA checkpoint and repair, kinases pathways, energetic and nucleotide metabolisms were the important biological process that found. We predicted the interactomes of 58 proteins under positive selection in IRRB. It is hoped our data will provide new clues as to the cellular pathways that are important for ionizing-radiation resistance. We have identified news proteins involved on DNA management which were not previously mentioned. It is an important input in addition to protein that studied. It does still work to deepen our study on these new proteins

  15. Enhanced radioresistance of behavioral reaction of rats adopted to hypoxia

    International Nuclear Information System (INIS)

    Sizan, E.P.

    1979-01-01

    Rats were adapted to hypoxia in the altitude chamber imitating the altitude of 5000 m with peaky ''ascents'' up to 8000 m every 60 min at the rates of ''ascent'' and ''descent'' of 40 m/sec. Adapted and intact animals were exposed to a dose of 400 rad at a dose rate of 20 rad/min. Rats adapted to oxygen deficiency and irradiated executed their conditioned reflexes much better than nonadapted ones

  16. Position automatic determination technology

    International Nuclear Information System (INIS)

    1985-10-01

    This book tells of method of position determination and characteristic, control method of position determination and point of design, point of sensor choice for position detector, position determination of digital control system, application of clutch break in high frequency position determination, automation technique of position determination, position determination by electromagnetic clutch and break, air cylinder, cam and solenoid, stop position control of automatic guide vehicle, stacker crane and automatic transfer control.

  17. Small, but Determined: Technological Determinism in Nanoscience

    OpenAIRE

    Cyrus C.M. Mody

    2004-01-01

    Analysis of technological determinism by historians, sociologists, and philosophers has declined in recent years. Yet understanding this topic is necessary, particularly in examining the dynamics of emerging technologies and their associated research areas. This is especially true of nanotechnology, which, because of its roots in futurist traditions, employs unusual variants on classical determinist arguments. In particular, nanotechnology orients much more strongly to the past and future tha...

  18. Cave age determination

    International Nuclear Information System (INIS)

    Anon.

    1998-01-01

    To determine the age of a cave we have to determine the age of elements which were created at the same moment when the cave was. Usually a cave is dug out by infiltration of acid waters. During this alteration process rocks free some aluminium and potassium ions. In Carlsbad and Lechuguilla caves, scientists have found alunite, this aluminium and potassium sulfate can be dated by using the carbon method of age determination. (A.C.)

  19. SIS - Status Determination

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Status Determination dataset within the Species Information System (SIS) contains information related to overfishing, overfished, and approaching overfished...

  20. Determination of cerium

    International Nuclear Information System (INIS)

    Stepin, V.V.; Kurbatova, V.I.; Fedorova, N.D.

    1980-01-01

    Techniques of cerium determination in steels and alloys are developed. Amperometric method of determination which is based on Ce(4) titration by a solution of double salt of sulfuric Fe(2) and ammonium when cerium amount exceeds 0.01% is suggested. Cerium is oxidated to tetravalent state by KMnO 4 . The elements interfering with the determination (Cr, Ni etc.) are separated by means of deposition. When cerium content exceeds 0.005% in steels and alloys the determination is carried out using photometric method with arsenazo 3 in hydrochloric medium (pH 1.8-2.3). Optimum concentration is 5-50 μg [ru

  1. Asteroids mass determination

    International Nuclear Information System (INIS)

    Hoffmann, M.

    1989-01-01

    Basic methods for asteroid mass determinations and their errors are discussed. New results and some current developments in the astrometric method are reviewed. New methods and techniques, such as electronic imaging, radar ranging and space probes are becoming important for asteroid mass determinations. Mass and density estimations on rotational properties and possible satelites are also discussed

  2. CATALYTIC KINETIC SPECTROPHOTOMETRIC DETERMINATION ...

    African Journals Online (AJOL)

    Preferred Customer

    acetylchlorophosphonazo(CPApA) by hydrogen peroxide in 0.10 M phosphoric acid. A novel catalytic kinetic-spectrophotometric method is proposed for the determination of copper based on this principle. Copper(II) can be determined spectrophotometrically ...

  3. Determinants of State Aid

    NARCIS (Netherlands)

    Buiren, K.; Brouwer, E.

    2010-01-01

    From economic theory we derive a set of hypotheses on the determination of state aid. Econometric analysis on EU state aid panel data is carried out to test whether the determinants we expect on the basis of theory, correspond to the occurrence of state aid in practice in the EU. We find that

  4. ATR confinement leakage determination

    International Nuclear Information System (INIS)

    Kuan, P.; Buescher, B.J.

    1998-01-01

    The air leakage rate from the Advanced Test Reactor (ATR) confinement is an important parameter in estimating hypothesized accidental releases of radiation to the environment. The leakage rate must be determined periodically to assure that the confinement has not degraded with time and such determination is one of the technical safety requirements of ATR operation. This paper reviews the methods of confinement leakage determination and presents an analysis of leakage determination under windy conditions, which can complicate the interpretation of the determined leakage rates. The paper also presents results of analyses of building air exchange under windy conditions. High wind can enhance air exchange and this could increase the release rates of radioisotopes following an accident

  5. Altered G1 checkpoint control determines adaptive survival responses to ionizing radiation

    International Nuclear Information System (INIS)

    Boothman, David A.; Meyers, Mark; Odegaard, Eric; Wang, Meizhi

    1996-01-01

    Adaptive survival responses (ASRs) are observed when cells become more resistant to a high dose of a cytotoxic agent after repeated low dose exposures to that agent or another genotoxic agent. Confluent (G 0 /G 1 ) human normal (GM2936B, GM2937A, AG2603, IMR-90), cancer-prone (XPV2359), and neoplastic (U1-Mel, HEp-2, HTB-152) cells were primed with repeated low doses of X-rays (ranging from 0.05-10 cGy/day for 4 days), then challenged with a high dose (290-450 cGy) on day 5. U1-Mel and HEp-2 cells showed greater than 2-fold transient survival enhancement when primed with 1-10 cGy. ASRs in U1-Mel or HEp-2 cells were blocked by cycloheximide or actinomycin D. Increases in cyclins A and D1 mRNAs were noted in primed compared to unirradiated U1-Mel and HEp-2 cells; however, only cyclin A protein levels increased. Cyclin D1 and proliferating cell nuclear antigen (PCNA) protein levels were constitutively elevated in HEp-2 and U1-Mel cells, compared to the other human normal and neoplastic cells examined, and were not altered by low or high doses of radiation. Low dose primed U1-Mel cells entered S-phase 4-6 h faster than unprimed U1-Mel cells upon low-density replating. Similar responses in terms of survival recovery, transcript and protein induction, and altered cell cycle regulation were not observed in the other human normal, cancer-prone or neoplastic cells examined. We hypothesize that only certain human cells can adapt to ionizing radiation by progressing to a point later in G 1 (the A point) where DNA repair processes and radioresistance can be induced. ASRs in human cells correlated well with constitutively elevated levels of PCNA and cyclin D1, as well as inducibility of cyclin A. We propose that a protein complex composed of cyclin D1, PCNA, and possibly cyclin A may play a role in cell cycle regulation and DNA repair, which determine ASRs in human cells

  6. Determinants of Actor Rationality

    DEFF Research Database (Denmark)

    Ellegaard, Chris

    Industrial companies must exercise influence on their suppliers (or supplier actors). Actor rationality is a central theme connected to this management task. In this article, relevant literature is studied with the purpose of shedding light on determinants of actor rationality. Two buyer-supplier...... relations are investigated in a multiple case study, leading to the proposal of various additional factors that determine and shape actor rationality. Moreover a conceptual model of rationality determinants in the buyer-supplier relation is proposed, a model that may help supply managers analyse...

  7. Calcium and magnesium determination

    International Nuclear Information System (INIS)

    Bhattacharya, S.K.

    1982-01-01

    The roles of calcium and magnesium in human health and disease have been extensively studied. Calcium and magnesium have been determined in biological specimens by atomic absorption spectroscopy using stiochiometric nitrous oxide-acetylene flame

  8. Commentary Sex determination

    Indian Academy of Sciences (India)

    PRAKASH KUMAR G

    2008-01-31

    ZW is reserved for female heterogamety.) The Radder et al study used lab incubation regimes that mimic temperature profiles of cool natural nests, so temperature probably determines sex at least occasionally in nature.

  9. Robust Growth Determinants

    OpenAIRE

    Doppelhofer, Gernot; Weeks, Melvyn

    2011-01-01

    This paper investigates the robustness of determinants of economic growth in the presence of model uncertainty, parameter heterogeneity and outliers. The robust model averaging approach introduced in the paper uses a flexible and parsi- monious mixture modeling that allows for fat-tailed errors compared to the normal benchmark case. Applying robust model averaging to growth determinants, the paper finds that eight out of eighteen variables found to be significantly related to economic growth ...

  10. Health determinants and podiatry.

    Science.gov (United States)

    Brodie, B S

    2001-09-01

    Public health and podiatry have a natural union both through historical development and a shared interest in prevention. Podiatry is considered in terms of health determinants such as income, social support, education and environment. The author considers that podiatry has a constructive role to play in the improvement of health and well-being in terms of the previously unrecognised relationship of the profession to the determinants of health and population health promotion.

  11. Determining postural stability

    Science.gov (United States)

    Lieberman, Erez (Inventor); Forth, Katharine E. (Inventor); Paloski, William H. (Inventor)

    2011-01-01

    A method for determining postural stability of a person can include acquiring a plurality of pressure data points over a period of time from at least one pressure sensor. The method can also include the step of identifying a postural state for each pressure data point to generate a plurality of postural states. The method can include the step of determining a postural state of the person at a point in time based on at least the plurality of postural states.

  12. Emergency operation determination system

    International Nuclear Information System (INIS)

    Miki, Tetsushi.

    1993-01-01

    The system of the present invention can determine an emergency operation coping with abnormal events occurring during nuclear plant operation without replying on an operator's judgement. That is, the system of the present invention comprises an intelligence base which divides and classifies the aims of the plant operation for the function, structure and operation manual and puts them into network. Degree of attainment for the extend of the status normality is determined on every aim of operation based on various kinds of measured data during plant operation. For a degree of attainment within a predetermined range, it is judged that an emergency operation is possible although this is in an abnormal state. Degree of emergency is determined by a fuzzy theory based on the degree of attainment, variation coefficient for the degree of attainment and the sensitivity to external disturbance as parameters. Priority for the degree of emergency on every operation aims is determined by comparison. Normality is successively checked for the determined operation aims. As a result, equipments as objects of abnormality suppressing operation are specified, and the operation amount of the equipments as objects are determined so that the measuring data are within a predetermined range. (I.S.)

  13. Determination method of radiostrontium

    International Nuclear Information System (INIS)

    1984-01-01

    This manual provides determination methods of strontium-90 and strontium-89 in the environment released from nuclear facilities, and it is a revised edition of the previous manual published in 1974. As for the preparation method of radiation counting sample, ion exchange method, oxalate separation method and solvent extraction method were adopted in addition to the method of fuming nitric acid separation adopted in the previous edition. Strontium-90 is determined by the separation and radioactivity determination of yttrium-90 in radioequilibrium with strontium-90. Strontium-89 is determined by subtraction of radioactivity of strontium-90 plus yttrium-90 from gross radioactivity of isolated strontium carbonate. Radioactivity determination should be carried out with a low-background 2 π-gas-flow counting system for the mounted sample on a filter having a chemical form of ferric hydroxide, yttrium oxalate or strontium carbonate. This manual describes sample preparation procedures as well as radioactivity counting procedures for environmental samples of precipitates as rain or snow, airborne dust, fresh water, sea water and soil, and also for ash sample made from biological or food samples such as grains, vegetables, tea leaves, pine needle, milk, marine organisms, and total diet, by employing a method of fuming nitric acid separation, ion exchange separation, oxalate precipitate separation or solvent extraction separation (only for an ash sample). Procedures for reagent chemicals preparation is also attached to this manual. (Takagi, S.)

  14. Statistical Attitude Determination

    Science.gov (United States)

    Markley, F. Landis

    2010-01-01

    All spacecraft require attitude determination at some level of accuracy. This can be a very coarse requirement of tens of degrees, in order to point solar arrays at the sun, or a very fine requirement in the milliarcsecond range, as required by Hubble Space Telescope. A toolbox of attitude determination methods, applicable across this wide range, has been developed over the years. There have been many advances in the thirty years since the publication of Reference, but the fundamentals remain the same. One significant change is that onboard attitude determination has largely superseded ground-based attitude determination, due to the greatly increased power of onboard computers. The availability of relatively inexpensive radiation-hardened microprocessors has led to the development of "smart" sensors, with autonomous star trackers being the first spacecraft application. Another new development is attitude determination using interferometry of radio signals from the Global Positioning System (GPS) constellation. This article reviews both the classic material and these newer developments at approximately the level of, with emphasis on. methods suitable for use onboard a spacecraft. We discuss both "single frame" methods that are based on measurements taken at a single point in time, and sequential methods that use information about spacecraft dynamics to combine the information from a time series of measurements.

  15. Airborne geoid determination

    DEFF Research Database (Denmark)

    Forsberg, René; Olesen, Arne Vestergaard; Bastos, L.

    2000-01-01

    Airborne geoid mapping techniques may provide the opportunity to improve the geoid over vast areas of the Earth, such as polar areas, tropical jungles and mountainous areas, and provide an accurate "seam-less" geoid model across most coastal regions. Determination of the geoid by airborne methods...... relies on the development of airborne gravimetry, which in turn is dependent on developments in kinematic GPS. Routine accuracy of airborne gravimetry are now at the 2 mGal level, which may translate into 5-10 cm geoid accuracy on regional scales. The error behaviour of airborne gravimetry is well......-suited for geoid determination, with high-frequency survey and downward continuation noise being offset by the low-pass gravity to geoid filtering operation. In the paper the basic principles of airborne geoid determination are outlined, and examples of results of recent airborne gravity and geoid surveys...

  16. Determinants of marriage dissolution

    Science.gov (United States)

    Rahim, Mohd Amirul Rafiq Abu; Shafie, Siti Aishah Mohd; Hadi, Az'lina Abdul; Razali, Nornadiah Mohd; Azid @ Maarof, Nur Niswah Naslina

    2015-10-01

    Nowadays, the number of divorce cases among Muslim couples is very worrisome whereby the total cases reported in 2013 increased by half of the total cases reported in the previous year. The questions on the true key factors of dissolution of marriage continue to arise. Thus, the objective of this study is to reveal the factors that contribute to the dissolution of marriage. A total of 181 cases and ten potential determinants were included in this study. The potential determinants considered were age at marriage of husband and wife, educational level of husband and wife, employment status of husband and wife, income of husband and wife, the number of children and the presence at a counseling session. Logistic regression analysis was used to analyze the data. The findings revealed that four determinants, namely the income of husband and wife, number of children and the presence at a counselling session were significant in predicting the likelihood of divorce among Muslim couples.

  17. Spacecraft Attitude Determination

    DEFF Research Database (Denmark)

    Bak, Thomas

    This thesis describes the development of an attitude determination system for spacecraft based only on magnetic field measurements. The need for such system is motivated by the increased demands for inexpensive, lightweight solutions for small spacecraft. These spacecraft demands full attitude...... determination based on simple, reliable sensors. Meeting these objectives with a single vector magnetometer is difficult and requires temporal fusion of data in order to avoid local observability problems. In order to guaranteed globally nonsingular solutions, quaternions are generally the preferred attitude...... is a detailed study of the influence of approximations in the modeling of the system. The quantitative effects of errors in the process and noise statistics are discussed in detail. The third contribution is the introduction of these methods to the attitude determination on-board the Ørsted satellite...

  18. Fluorescence uranium determination

    International Nuclear Information System (INIS)

    Fernandez Cellini, R.; Crus Castillo, F. de la; Barrera Pinero, R.

    1960-01-01

    An equipment for analysis of uranium by fluorescence was developed in order to determine it at such a low concentration that it can not be determined by the most sensible analytical methods. this new fluorimeter was adapted to measure the fluorescence emitted by the phosphorus sodium fluoride-sodium carbonate-potasium carbonate-uranyl, being excited by ultraviolet light of 3,650 A the intensity of the light emitted was measure with a photomultiplicator RCA 5819 and the adequate electronic equipment. (Author) 19 refs

  19. Plasma beta HCG determination

    International Nuclear Information System (INIS)

    Amaral, L.B.D.; Pinto, J.C.M.; Linhares, E.; Linhares, Estevao

    1981-01-01

    There are three important indications for the early diagnosis of pregnancy through the determination of the beta sub-unit of chorionic gonadotrophin using radioimmunoassay: 1) some patient's or doctor's anxiety to discover the problem; 2) when it will be necessary to employ diagnostic or treatment procedures susceptible to affect the ovum; and 3) in the differential diagnosis of amenorrhoea, uterine hemorrhage and abdominal tumors. Other user's are the diagnosis of missed absortion, and the diagnosis and follow-up of chrorioncarcinoma. The AA. studied 200 determinations of plasma beta-HCG, considering the main difficulties occuring in the clinical use of this relevant laboratory tool in actual Obstetrics. (author) [pt

  20. Determining gold content

    International Nuclear Information System (INIS)

    Clayton, C.G.; Wormald, M.R.

    1981-01-01

    A method for determining the gold content of a material, comprises irradiating a body of the material with neutrons and determining the intensity of γ-rays having an energy of 279 keV arising from the reaction 179 Au(nn') 179 Au → 279 keV. The apparatus has means for conveying the materials past an assembly, which has a neutron source, which does not produce neutrons having sufficient energy to excite fast neutron reactions in non-auriferous constituents. (author)

  1. Are risks quantitatively determinable

    International Nuclear Information System (INIS)

    Buetzer, P.

    1985-01-01

    ''Chemical risks'' can only be determined with accurate figures in a few extraordinary cases. The difficulties lie, as has been shown by the example of the Flixborough catastrophe, mostly in the determination of the probabilities of occurrence. With a rough semiquantitative estimate of the potential hazards and the corresponding probabilities we can predict the risks with astonishing accuracy. Statistical data from incidents in the chemical industry are very useful, and they also show that ''chemical catastrophes'' are only to a very small extent initiated by uncontrolled chemical reactions. (orig.) [de

  2. Particle size determination

    International Nuclear Information System (INIS)

    Burr, K.J.

    1979-01-01

    A specification is given for an apparatus to provide a completely automatic testing cycle to determine the proportion of particles of less than a predetermined size in one of a number of fluid suspensions. Monitoring of the particle concentration during part of the process can be carried out by an x-ray source and detector. (U.K.)

  3. Determining TOC in Waters

    Science.gov (United States)

    Kehoe, Thomas J.

    1977-01-01

    The instrumental method for detecting total organic carbon (TOC) in water samples is detailed. The method's limitations are discussed and certain precautions that must be taken are emphasized. The subject of TOC versus COD and BOD is investigated and TOC is determined to be a valid indication of biological demand. (BT)

  4. Determining average yarding distance.

    Science.gov (United States)

    Roger H. Twito; Charles N. Mann

    1979-01-01

    Emphasis on environmental and esthetic quality in timber harvesting has brought about increased use of complex boundaries of cutting units and a consequent need for a rapid and accurate method of determining the average yarding distance and area of these units. These values, needed for evaluation of road and landing locations in planning timber harvests, are easily and...

  5. SHORT COMMUNICATION POTENTIOMETRIC DETERMINATION ...

    African Journals Online (AJOL)

    a

    SHORT COMMUNICATION. POTENTIOMETRIC DETERMINATION OF K+ IONS USING A K+-SELECTIVE. ELECTRODE WITH MACROCYCLIC LIQUID MEMBRANE. Cezar Spinu*, Marian Isvoranu, Maria Pleniceanu and Cristian Tigae. Faculty of Chemistry, University of Craiova, A.I. Cuza 13, Craiova, Romania. (Received ...

  6. Gender determination in populus

    Energy Technology Data Exchange (ETDEWEB)

    McLetchie, D.N. [Univ. of Kentucky, Lexington, KY (United States). Dept. of Biological Sciences; Tuskan, G.A. [Oak Ridge National Lab., TN (United States)

    1994-12-31

    Gender, the expression of maleness or femaleness, in dioecious plants has been associated with changes in morphology, physiology, ecological position, and commercial importance of several species, including members of the Salicaceae family. Various mechanisms have been proposed to explain the expression of gender in Salicaceae, including sex chromosomes, simple Mendelian genes, quantitative genes, environment, and genotype-by-environment interactions. Published reports would favor a genetic basis for gender. The objective of this study was to identify molecular markers associated with gender in a segregating family of hybrid poplars. Bulked segregant analysis and chi-squared analysis were used to test for the occurrence of sex chromosomes, individual loci, and chromosome ratios (i.e., ploidy levels) as the mechanisms for gender determination. Examination of 2488 PCR based RAPD markers from 1219 primers revealed nine polymorphic bands between male and female bulked samples. However, linkage analysis indicated that none of these markers were significantly associated with gender. Chisquared results for difference in male-to-female ratios between diploid and triploid genotypes also revealed no significant differences. These findings suggest gender is not controlled via sex chromosomes, simple Mendelian loci or ratios of autosome to gender-determining loci. It is possible that gender is determined genetically by regions of the genome not sampled by the tested markers or by a complex of loci operating in an additive threshold manner or in an epistatic manner. It is also possible that gender is determined environmentally at an early zygote stage, canalizing gender expression.

  7. Waste Determination Equivalency - 12172

    Energy Technology Data Exchange (ETDEWEB)

    Freeman, Rebecca D. [Savannah River Remediation (United States)

    2012-07-01

    The Savannah River Site (SRS) is a Department of Energy (DOE) facility encompassing approximately 800 square kilometers near Aiken, South Carolina which began operations in the 1950's with the mission to produce nuclear materials. The SRS contains fifty-one tanks (2 stabilized, 49 yet to be closed) distributed between two liquid radioactive waste storage facilities at SRS containing carbon steel underground tanks with storage capacities ranging from 2,800,000 to 4,900,000 liters. Treatment of the liquid waste from these tanks is essential both to closing older tanks and to maintaining space needed to treat the waste that is eventually vitrified or disposed of onsite. Section 3116 of the Ronald W. Reagan National Defense Authorization Act of Fiscal Year 2005 (NDAA) provides the Secretary of Energy, in consultation with the Nuclear Regulatory Commission (NRC), a methodology to determine that certain waste resulting from prior reprocessing of spent nuclear fuel are not high-level radioactive waste if it can be demonstrated that the waste meets the criteria set forth in Section 3116(a) of the NDAA. The Secretary of Energy, in consultation with the NRC, signed a determination in January 2006, pursuant to Section 3116(a) of the NDAA, for salt waste disposal at the SRS Saltstone Disposal Facility. This determination is based, in part, on the Basis for Section 3116 Determination for Salt Waste Disposal at the Savannah River Site and supporting references, a document that describes the planned methods of liquid waste treatment and the resulting waste streams. The document provides descriptions of the proposed methods for processing salt waste, dividing them into 'Interim Salt Processing' and later processing through the Salt Waste Processing Facility (SWPF). Interim Salt Processing is separated into Deliquification, Dissolution, and Adjustment (DDA) and Actinide Removal Process/Caustic Side Solvent Extraction Unit (ARP/MCU). The Waste Determination was signed

  8. Determinants of translation ambiguity

    Science.gov (United States)

    Degani, Tamar; Prior, Anat; Eddington, Chelsea M.; Arêas da Luz Fontes, Ana B.; Tokowicz, Natasha

    2016-01-01

    Ambiguity in translation is highly prevalent, and has consequences for second-language learning and for bilingual lexical processing. To better understand this phenomenon, the current study compared the determinants of translation ambiguity across four sets of translation norms from English to Spanish, Dutch, German and Hebrew. The number of translations an English word received was correlated across these different languages, and was also correlated with the number of senses the word has in English, demonstrating that translation ambiguity is partially determined by within-language semantic ambiguity. For semantically-ambiguous English words, the probability of the different translations in Spanish and Hebrew was predicted by the meaning-dominance structure in English, beyond the influence of other lexical and semantic factors, for bilinguals translating from their L1, and translating from their L2. These findings are consistent with models postulating direct access to meaning from L2 words for moderately-proficient bilinguals. PMID:27882188

  9. Determinants for gallstone formation

    DEFF Research Database (Denmark)

    Shabanzadeh, Daniel Monsted; Sorensen, Lars Tue; Jørgensen, Torben

    2016-01-01

    . Gallstone incidence was assessed through repeated ultrasound examinations. Body mass index (BMI), blood pressure, self-rated health, lifestyle variables, blood lipids, and use of female sex hormones were measured at the baseline examination. Statistical analyses included logistic regression. Based...... re-examination were followed-up completely (mean 11.6 years, N = 2848). The overall cumulative incidence of gallstones was 0.60% per year. Independent positive determinants for incident gallstones were age, female sex, non-high density lipoprotein (non-HDL) cholesterol, and gallbladder polyps...... associations were found for blood pressure, smoking, alcohol consumption, HDL cholesterol, or triglycerides in meta-analyses. Conclusions: Age, female sex, BMI, non-HDL cholesterol, and polyps are independent determinants for gallstone formation. Incident gallstones and the metabolic syndrome share common risk...

  10. Determining Optimal Decision Version

    Directory of Open Access Journals (Sweden)

    Olga Ioana Amariei

    2014-06-01

    Full Text Available In this paper we start from the calculation of the product cost, applying the method of calculating the cost of hour- machine (THM, on each of the three cutting machines, namely: the cutting machine with plasma, the combined cutting machine (plasma and water jet and the cutting machine with a water jet. Following the calculation of cost and taking into account the precision of manufacturing of each machine, as well as the quality of the processed surface, the optimal decisional version needs to be determined regarding the product manufacturing. To determine the optimal decisional version, we resort firstly to calculating the optimal version on each criterion, and then overall using multiattribute decision methods.

  11. On Psychic Determinism.

    Science.gov (United States)

    Brown, Robin Gordon

    2017-06-01

    A confusion persists in the psychoanalytic literature regarding the concept of psychic determinism. Two authors are cited in whose works the concept is identified as foundational to psychoanalysis, in the one case as a "fundamental hypothesis" (Charles Brenner) and in the other as an "underlying presupposition" or assumption (Linda A.W. Brakel). Both claims are based on a conflation of the concept Freud had in mind with a philosophical doctrine going by the same name but meaning something quite different. The philosophical doctrine has no place in psychoanalysis at all, and Freud's concept does not play a foundational role there. In a second section a restricted concept of psychic determinism is critically examined. A third section deals with the impact of that restricted concept on clinical theory and contemporary controversies about clinical practice. Finally, some possible reasons for this confusion are suggested.

  12. Determination of nickel-63

    International Nuclear Information System (INIS)

    Poletiko, C.

    1988-01-01

    The research of activation products in the environment is often centered on cobalt-60 or other gamma emitters, since pure beta emitters require time consuming separations to be counted. However, some beta emitters must be checked because they have a build up in the environment, leading to potential hazards. Among these nuclides, there is nickel-63 which is a pure, soft beta emitter (67 keV) with a long half-life (100 years). A chemical separation, providing good results, was developed. Such a separation is based upon nickel carrier addition in the sample than DMG complex formation and isolation; after elimination of solvent. DMG complex is destroyed. Chemical yield is determined by flame atomic absorption measurement and nickel-63 counted by liquid scintillation. The described procedure allows the determination of low-level activities in different samples (soils, effluents, etc.). Detection limits are close to 0.1 Bq per sample

  13. Cyanides: decomposition and determination

    International Nuclear Information System (INIS)

    Gilath, I.; Cohen, L.

    1977-08-01

    Different cyanide destruction methods such as electrolysis (with and without the addition of salt), hypochlorite treatment and ion exchange detoxication were evaluated on a laboratory scale using model solutions. Parameters were determined for the optimal operation of the investigated processes. Analytical methods were adapted for concentrations and compositions of interest. An easy and rapid method of complex cyanide breakdown by ion exchange treatment was developed for analytical purposes. (author)

  14. Ion Mass Determination

    DEFF Research Database (Denmark)

    2010-01-01

    An apparatus (100) is described for determining the mass of ions, the apparatus configured to hold a plasma (101 ) having a plasma potential. The apparatus (100) comprises an electrode (102) having a surface extending in a surface plane and an insulator (104) interfacing with the electrode (102......, and a processing unit (108) configured to interpret the detected impact locations in terms of the mass of the impacting ions....

  15. Satellite Photometric Error Determination

    Science.gov (United States)

    2015-10-18

    Satellite Photometric Error Determination Tamara E. Payne, Philip J. Castro, Stephen A. Gregory Applied Optimization 714 East Monument Ave, Suite...advocate the adoption of new techniques based on in-frame photometric calibrations enabled by newly available all-sky star catalogs that contain highly...filter systems will likely be supplanted by the Sloan based filter systems. The Johnson photometric system is a set of filters in the optical

  16. Stochastic split determinant algorithms

    International Nuclear Information System (INIS)

    Horvatha, Ivan

    2000-01-01

    I propose a large class of stochastic Markov processes associated with probability distributions analogous to that of lattice gauge theory with dynamical fermions. The construction incorporates the idea of approximate spectral split of the determinant through local loop action, and the idea of treating the infrared part of the split through explicit diagonalizations. I suggest that exact algorithms of practical relevance might be based on Markov processes so constructed

  17. Determination of vanadium

    International Nuclear Information System (INIS)

    Stepin, V.V.; Kurbatova, V.I.; Fedorova, N.D.

    1980-01-01

    Titrimetric and potentiometric methods of vanadium determination in ferrovanadium are developed. The essence of the titrimetric method using phenylanthranilic acid as indicator is in the following. Ferrovanadium weighed amount is dissolved in H 2 SO 4 , vanadium is oxidated by potassium permanganate to V(5) and is titrated by a solution of double salt of sulfuric Fe(2) and ammonium in the presence of indicator. Potentiometric titration is carried out using the same indicator [ru

  18. Uranium determination in water

    International Nuclear Information System (INIS)

    Prudenzo, E.J.; Puga, Maria J.; Cerchietti, Maria L.R.; Arguelles, Maria G.

    2005-01-01

    In our laboratory, a procedure has been assessed to determine uranium content of water in normal situations. The method proposed without sample pre-treatment, is simple and rapid. Uranium mass is measured by fluorimetry. For calculation of detection limit (Ld) and quantification level (Lq) we used blank samples and the results were analyzed for different statistical test. The calculation of total propagated uncertainty and sources contribution on real samples are presented. (author)

  19. Determination of vanadium

    International Nuclear Information System (INIS)

    Stepin, V.V.; Kurbatova, V.I.; Fedorova, N.D.

    1980-01-01

    Techniques of vanadium determination in steels and alloys are developed. Extraction-photometric method with N-phenyl-benzohydroxamic acid when V content is 0.005-0.5% is suggested. Molar coefficient of the complex quenching at lambdasub(max)=530 nm constitutes 5750. Optimum concentration is 15-150 μg per 25 ml of the solution, determination limit is 0.05 μg/ml. Chloroform is an extracting agent. A photometric method with acetohydrazide of anthranilic acid is suggested for the analysis of alloyed steels at V content 0.03-1%. The lower limit of V determination constitutes 0.64 μg/ml. Effect of Fe is removed using phosphoric acid. Amperometric method for steels and alloys at V content from 0.05 to 5% and for steels and alloys containing more than 3% W and Cr is also developed. The method is based on amperometric titration with solution of double sulfuric salt of Fe(2) and ammonium [ru

  20. ITAR: A modified TAR method to determine depth dose distribution for an ophthalmic device that performs kilovoltage x-ray pencil-beam stereotaxy

    International Nuclear Information System (INIS)

    Hanlon, Justin; Chell, Erik; Firpo, Michael; Koruga, Igor

    2014-01-01

    Purpose: New technology has been developed to treat age-related macular degeneration (AMD) using 100 kVp pencil-beams that enter the patient through the radio-resistant sclera with a depth of interest between 1.6 and 2.6 cm. Measurement of reference and relative dose in a kilovoltage x-ray beam with a 0.42 cm diameter field size and a 15 cm source to axis distance (SAD) is a challenge that is not fully addressed in current guidelines to medical physicists. AAPM's TG-61 gives dosimetry recommendations for low and medium energy x-rays, but not all of them are feasible to follow for this modality. Methods: An investigation was conducted to select appropriate equipment for the application. PTW's Type 34013 Soft X-Ray Chamber (Freiburg, Germany) and CIRS's Plastic Water LR (Norfolk, VA) were found to be the best available options. Attenuation curves were measured with minimal scatter contribution and thus called Low Scatter Tissue Air Ratio (LSTAR). A scatter conversion coefficient (C scat ) was derived through Monte Carlo radiation transport simulation using MCNPX (LANL, Los Alamos, NM) to quantify the difference between a traditional TAR curve and the LSTAR curve. A material conversion coefficient (C mat ) was determined through experimentation to evaluate the difference in attenuation properties between water and Plastic Water LR. Validity of performing direct dosimetry measurements with a source to detector distance other than the treatment distance, and therefore a different field size due to a fixed collimator, was explored. A method—Integrated Tissue Air Ratio (ITAR)—has been developed that isolates each of the three main radiological effects (distance from source, attenuation, and scatter) during measurement, and integrates them to determine the dose rate to the macula during treatment. Results: LSTAR curves were determined to be field size independent within the range explored, indicating that direct dosimetry measurements may be performed with a source to

  1. ITAR: A modified TAR method to determine depth dose distribution for an ophthalmic device that performs kilovoltage x-ray pencil-beam stereotaxy

    Energy Technology Data Exchange (ETDEWEB)

    Hanlon, Justin, E-mail: jhanlon@orayainc.com; Chell, Erik; Firpo, Michael; Koruga, Igor [Oraya Therapeutics, Inc., Newark, California 94560 (United States)

    2014-02-15

    Purpose: New technology has been developed to treat age-related macular degeneration (AMD) using 100 kVp pencil-beams that enter the patient through the radio-resistant sclera with a depth of interest between 1.6 and 2.6 cm. Measurement of reference and relative dose in a kilovoltage x-ray beam with a 0.42 cm diameter field size and a 15 cm source to axis distance (SAD) is a challenge that is not fully addressed in current guidelines to medical physicists. AAPM's TG-61 gives dosimetry recommendations for low and medium energy x-rays, but not all of them are feasible to follow for this modality. Methods: An investigation was conducted to select appropriate equipment for the application. PTW's Type 34013 Soft X-Ray Chamber (Freiburg, Germany) and CIRS's Plastic Water LR (Norfolk, VA) were found to be the best available options. Attenuation curves were measured with minimal scatter contribution and thus called Low Scatter Tissue Air Ratio (LSTAR). A scatter conversion coefficient (C{sub scat}) was derived through Monte Carlo radiation transport simulation using MCNPX (LANL, Los Alamos, NM) to quantify the difference between a traditional TAR curve and the LSTAR curve. A material conversion coefficient (C{sub mat}) was determined through experimentation to evaluate the difference in attenuation properties between water and Plastic Water LR. Validity of performing direct dosimetry measurements with a source to detector distance other than the treatment distance, and therefore a different field size due to a fixed collimator, was explored. A method—Integrated Tissue Air Ratio (ITAR)—has been developed that isolates each of the three main radiological effects (distance from source, attenuation, and scatter) during measurement, and integrates them to determine the dose rate to the macula during treatment. Results: LSTAR curves were determined to be field size independent within the range explored, indicating that direct dosimetry measurements may be

  2. Determination of zirconium

    International Nuclear Information System (INIS)

    Iha, C.; Sood, S.P.; Sato, I.M.

    1985-01-01

    The analysis of Zr and Hf by X-ray fluorescence was studied. The thin film technique for sample preparation by deposition of precipitate on the filter paper was used. The K sub(α) line of Zr and L sub(β) 1 line of Hf were considered for the analysis. The behaviour of fluorescence intensity ratio with the corresponding mass ratio was also studied. The direct determination of Hf in concentrations between 2 and 95% in samples without any separation was investigated. For Hf concentrations lower than 2%, a method for its enrichment was standardized. (Author) [pt

  3. LUMINESCENCE DETERMINATION OF ETODOLAC

    Directory of Open Access Journals (Sweden)

    A. V. Yegorova

    2015-02-01

    Full Text Available A highly sensitive, simple and rapid method for determination of non-steroidal anti- inflammatory drug – etodolac (Et in washings from surfaces of pharmaceutical equipment have been proposed. The intensity of native luminescence of water-n-propanol solutions of etodolac (λex= 274 nm; λlum= 350 nm was used as the analytical signal. The calibration graph is linear in the concentration range 0.014-2.3 μg/ml, the limit of detection is 0.5 ng/ml.

  4. Spectrophotometric Determination of Ezetimibe

    Directory of Open Access Journals (Sweden)

    P. Baby Sudha Lakshmi

    2010-01-01

    Full Text Available Two simple, sensitive, selective and accurate spectro-photometric methods (Method A and Method B for the determination of eztimibe in bulk drug and pharmaceutical formulations (tablets have been described. Method A and B are based on the redox/complex formation reaction of drug with 1,10-phenanthroline and hexacyano-ferrate(III in presence of ferric chloride to form coloured chromogens exhibiting λmax at 510 and 740 nm respectively. The results of analysis for the two methods have been validated statistically and by recovery studies. The results are compared with those obtained using UV spectrophotometric method in alcohol at 231.7 nm.

  5. Potentiometric determination of molybdenum

    International Nuclear Information System (INIS)

    Rusina, O.N.; Gorbatkova, B.Kh.

    1977-01-01

    Potentiometric titration by lead acetate is used to determine molybdenum in the form of molybdate ions. The behaviour of bimetallic electrode couples, i.e. tungsten-lead, platinum-lead, lead-carbon electrode, molybdenum-carbon electrode platinum-molibdenum has been investigated. The greatest jump of the potential in the finite point is observed for platinum-molybdenum electrode couple (150 mV/ml at pH 4.0-5.5). The limiting concentration of molybdenum in potentiometric titration by lead acetate is 2.8x10 -4 M. The measurements are accurate to within +-0.1%

  6. Determinants of capital structure.

    Science.gov (United States)

    McCue, M J; Ozcan, Y A

    1992-01-01

    This study analyzes the determinants of hospital capital structure in a new market setting that are created by the financial pressures of prospective payment and the intense price competition among hospitals. Using California data, the study found hospital system affiliation, bed size, growth rate in revenues, operating risk, and asset structure affected both short- and long-term debt borrowings. In addition, percentage of uncompensated care, profitability, and payer mix influenced short-term borrowings while market conditions and ownership affected long-term borrowings. Most significant of all is the finding that smaller hospitals tend to borrow more, possibly because they cannot generate funds internally.

  7. Determination of polynuclear hydrocarbons

    Energy Technology Data Exchange (ETDEWEB)

    Lodge, Jr, J P

    1963-01-01

    At the present time, the method of choice for the determination of polynuclear hydrocarbons appears to be the following, (a) extraction of the benzene-soluble fraction from the gross collected particulate matter, (b) one pass through a chromatographic column of partially deactivated alumina, (c) spectral examination of the fractions and (d) the application of appropriate chemical tests as indicated by the previous step. Using this method, the presence of pyrene, fluoranthene, one of the benzofluorenes, chrysens, benz(a)anthracene, benzo(a)pyrene, benzo(e)pyrene, benzo(k)fluoranthene, anthanthrene, and coronene was demonstrated in the air of numerous American cities, and benzo(a)pyrene was measured at some 130 sites. Invaluable as such accurate determinations may be for research purposes, they are still too costly and time-consuming for routine survey purposes. While studies on the subject are by no means complete, they indicate the validity of piperonal chloride test as a general index of polycyclic hydrocarbons. This procedure is described in this paper. 7 references.

  8. Determinants of Discretionary Investments

    Directory of Open Access Journals (Sweden)

    K. S. Sujit

    2016-03-01

    Full Text Available Theoretical and empirical studies have focused on discretionary investments such as research and development (R&D and advertisement as value-creating activities. This empirical research article examines the determinants of the discretionary investment policy of food sector firms in India. The study aims to analyze the impact of financial policies and firm characteristics on the discretionary investment strategy of the food industry firms. The article uses the partial least squares structural equation modeling (PLS-SEM to understand the drivers of discretionary investment policy of food sector firms. The study finds that investment policy of firms is a major determinant of profitability of food sector firms. Higher investments in capital expenditures and working capital result in higher profitability. Management efficiency significantly influences firm profitability. The results suggest that riskier firms in food sector might focus on R&D investments as a strategy to generate more cash flows. Size of firm is negatively related to R&D intensity. Smaller firms in food sector tend to invest more in R&D. The study does not provide evidence to suggest that profitable firms invest more in R&D activities.

  9. Determination of radar MTF

    Energy Technology Data Exchange (ETDEWEB)

    Chambers, D. [Lawrence Livermore National Lab., CA (United States)

    1994-11-15

    The ultimate goal of the Current Meter Array (CMA) is to be able to compare the current patterns detected with the array with radar images of the water surface. The internal wave current patterns modulate the waves on the water surface giving a detectable modulation of the radar cross-section (RCS). The function relating the RCS modulations to the current patterns is the Modulation Transfer Function (MTF). By comparing radar images directly with co-located CMA measurements the MTF can be determined. In this talk radar images and CMA measurements from a recent experiment at Loch Linnhe, Scotland, will be used to make the first direct determination of MTF for an X and S band radar at low grazing angles. The technical problems associated with comparing radar images to CMA data will be explained and the solution method discussed. The results suggest the both current and strain rate contribute equally to the radar modulation for X band. For S band, the strain rate contributes more than the current. The magnitude of the MTF and the RCS modulations are consistent with previous estimates when the wind is blowing perpendicular to the radar look direction.

  10. Determinants of Network Outcomes

    DEFF Research Database (Denmark)

    Ysa, Tamyko; Sierra, Vicenta; Esteve, Marc

    2014-01-01

    The literature on network management is extensive. However, it generally explores network structures, neglecting the impact of management strategies. In this article we assess the effect of management strategies on network outcomes, providing empirical evidence from 119 urban revitalization...... networks. We go beyond current work by testing a path model for the determinants of network outcomes and considering the interactions between the constructs: management strategies, trust, complexity, and facilitative leadership. Our results suggest that management strategies have a strong effect on network...... outcomes and that they enhance the level of trust. We also found that facilitative leadership has a positive impact on network management as well as on trust in the network. Our findings also show that complexity has a negative impact on trust. A key finding of our research is that managers may wield more...

  11. Substoichiometric determination of phosphorus

    International Nuclear Information System (INIS)

    Shigematsu, T.; Kudo, K.

    1981-01-01

    Phosphorus in orchard leaves (NBS SRM-1571) and spinach (SRM-1570) was determined by various substoichiometric analytical methods such as the direct method, Gravshchenko's method and the method of carrier amount variation. All samples were labelled with 32 P radioisotope. The data obtained by the method of carrier amount variation were also treated by the method of least squares instead of De Voe's method. Phosphorus concentration in orchard leaves was 0.206+-0.011% by the direct method, 0.219+-0.011% by Gravshchenko's method, 0.211+-0.011% by the method of carrier amount variation and 0.207+-0.007% by the method of least squares, respectively. These values agree with the value reported by NBS (0.21+-0.01%). Furthermore, these concentrations obtained by various substoichiometric methods were compared with those by radioactivation reported in a previous paper. (author)

  12. Polarographic determination of ruthenium

    International Nuclear Information System (INIS)

    Li Jifu; Duan Shirong; Wu Xi

    1989-01-01

    It is suggested to use 0.5 mol/l HClO 4 -0.5 mol/l NaNO 3 -0.1 mol/l NaClO 4 as supporting electrolyte for determining ruthenium. In the supporting electrolyte there is a clear polarographic wave of ruthenium (IV) at -0.8 V vs. SCE. The wave height of ruthenium(IV) is linear in the range from 0.1 to 0.4 μg. ml -1 . The effect of the component of supporting electroylte and the other ion in the samples on the measurement of ruthenium are studied. The analysis methods for measuring ruthenium in both acidic or basic imitative radioactive waste solutions which is used in study of glass solidification are worked out. Imitative samples are analysised

  13. Initiating events frequency determination

    International Nuclear Information System (INIS)

    Simic, Z.; Mikulicic, V.; Vukovic, I.

    2004-01-01

    The paper describes work performed for the Nuclear Power Station (NPS). Work is related to the periodic initiating events frequency update for the Probabilistic Safety Assessment (PSA). Data for all relevant NPS initiating events (IE) were reviewed. The main focus was on events occurring during most recent operating history (i.e., last four years). The final IE frequencies were estimated by incorporating both NPS experience and nuclear industry experience. Each event was categorized according to NPS individual plant examination (IPE) initiating events grouping approach. For the majority of the IE groups, few, or no events have occurred at the NPS. For those IE groups with few or no NPS events, the final estimate was made by means of a Bayesian update with general nuclear industry values. Exceptions are rare loss-of-coolant-accidents (LOCA) events, where evaluation of engineering aspects is used in order to determine frequency.(author)

  14. What determines our behavior

    Directory of Open Access Journals (Sweden)

    Marko Radovan

    2001-06-01

    Full Text Available In article Ajzen-Fishbein's attitude-behavior model called 'Theory of reasoned action' and Albert Bandura's Model of reciprocal determinism are presented. Both models are a part of social-cognitive paradigm which characterizes behavior with evaluation of different goals. Ajzen and Fishbein (1973; 1980 proposed that specific behavior are predictable from specific behavioral intentions. These intentions are a function of two components: the attitude toward the act in question and percieved normative expectations of reference group. On the other hand Bandura (1986; 1997 claims that person's motivation for a specific behavior and direction toward a specific social object respectively, reflects perception of his or hers self-efficacy beliefs. Some of the findings concerning the synthesis of the two models are also reviewed.

  15. Tritium determination in water

    International Nuclear Information System (INIS)

    Gavini, Ricardo M.

    2008-01-01

    An analytical procedure for the determination of tritium in water is described in this paper. The determination is carried out in presence of other radionuclides, such as Fe-55, Ni-63, Mn-54, Zn-65, Co-60, Cd-109, Sr-90, Cs-134 and Cs-137. The method consists in a simple distillation stage prior to measurement by liquid scintillation counting. The samples containing beta and gamma emitters are conditioned with a (NO 3 ) 2 Pb solution and Na(OH) up to pH = 7 - 8. This produces lead hydroxide precipitation that allows fixing volatile elements, which could be transported together with tritium, and may increase the extinction degree of the sample or interfere with the counting process. Special attention must be paid if presence of Fe-55 (E max ∼ 5.95 keV) is suspected as it might not be distinguished from tritium (E max ∼ 18 keV), leading to an overestimation of tritium activity. Different tests were carried to obtain the optimum method conditions, to achieve the purification of the tritium and a pH near to 7 in the distilled. The detection limit (2σ) was 8.0 Bq/l and the distillation performance was 98.3 %. This technique was applied to water samples containing Fe-55 and other gamma radionuclides in 1M hydrochloric acid media in successive Environmental Measurements Laboratory (EML), U.S. Department of Energy (DOE) intercomparison programs. The results obtained were very satisfactory and are presented in this paper. (author)

  16. Significant Radionuclides Determination

    Energy Technology Data Exchange (ETDEWEB)

    Jo A. Ziegler

    2001-07-31

    The purpose of this calculation is to identify radionuclides that are significant to offsite doses from potential preclosure events for spent nuclear fuel (SNF) and high-level radioactive waste expected to be received at the potential Monitored Geologic Repository (MGR). In this calculation, high-level radioactive waste is included in references to DOE SNF. A previous document, ''DOE SNF DBE Offsite Dose Calculations'' (CRWMS M&O 1999b), calculated the source terms and offsite doses for Department of Energy (DOE) and Naval SNF for use in design basis event analyses. This calculation reproduces only DOE SNF work (i.e., no naval SNF work is included in this calculation) created in ''DOE SNF DBE Offsite Dose Calculations'' and expands the calculation to include DOE SNF expected to produce a high dose consequence (even though the quantity of the SNF is expected to be small) and SNF owned by commercial nuclear power producers. The calculation does not address any specific off-normal/DBE event scenarios for receiving, handling, or packaging of SNF. The results of this calculation are developed for comparative analysis to establish the important radionuclides and do not represent the final source terms to be used for license application. This calculation will be used as input to preclosure safety analyses and is performed in accordance with procedure AP-3.12Q, ''Calculations'', and is subject to the requirements of DOE/RW-0333P, ''Quality Assurance Requirements and Description'' (DOE 2000) as determined by the activity evaluation contained in ''Technical Work Plan for: Preclosure Safety Analysis, TWP-MGR-SE-000010'' (CRWMS M&O 2000b) in accordance with procedure AP-2.21Q, ''Quality Determinations and Planning for Scientific, Engineering, and Regulatory Compliance Activities''.

  17. Listed waste determination report

    International Nuclear Information System (INIS)

    1993-06-01

    On September 23, 1988, the US Environmental Protection Agency (EPA) published a notice clarifying interim status requirements for the management of radioactive mixed waste thereby subjecting the Idaho National Engineering Laboratory (INEL) and other applicable Department of Energy (DOE) sites to regulation under the Resource Conservation and Recovery Act (RCRA). Therefore, the DOE was required to submit a Part A Permit application for each treatment, storage, and disposal (TSD) unit within the INEL, defining the waste codes and processes to be regulated under RCRA. The September 1990 revised Part A Permit application, that was approved by the State of Idaho identified 101 potential acute and toxic hazardous waste codes (F-, P-, and U- listed wastes according to 40 CFR 261.31 and 40 CFR 261.33) for some TSD units at the Idaho Chemical Processing Plant. Most of these waste were assumed to have been introduced into the High-level Liquid Waste TSD units via laboratory drains connected to the Process Equipment Waste (PEW) evaporator (PEW system). At that time, a detailed and systematic evaluation of hazardous chemical use and disposal practices had not been conducted to determine if F-, P-, or Unlisted waste had been disposed to the PEW system. The purpose of this investigation was to perform a systematic and detailed evaluation of the use and disposal of the 101 F-, P-, and Unlisted chemicals found in the approved September 1990 Part A Permit application. This investigation was aimed at determining which listed wastes, as defined in 40 CFR 261.31 (F-listed) and 261.33 (P ampersand Unlisted) were discharged to the PEW system. Results of this investigation will be used to support revisions to the RCRA Part A Permit application

  18. Titrimetric determination of ruthenium

    International Nuclear Information System (INIS)

    Velichko, V.V.; Belyaeva, T.I.; Kudinova, V.K.; Usatenko, Yu.I.

    1978-01-01

    Titration of ruthenium(4) hydrochloric-acid solutions with Mohr's salt, hydroquinone, and thiourea has been studied with the use of biampero- and potentiometric indication of the titration end point (t.e.p.) Potentiometric and amperometric indication of the t.e.p. is applicable when Ru(4) concentration is from 20 to 6000 mkg in 20 ml of the titrated solution; biamperometric indication can be used at a concentration of 5-1000 mkg in the same volume. It has been established that titration of Ru(4) (in the form of the Na 2 RuCl 6 solution) with Mohr's salt is not hindered by the presence of 1000-fold excess of alkaline and alkali-earth metals, Al, Ti(4), Mn(2), Cr(3), Fe(3), Co, Ni, Cu, Zn, Ga, Ge(4), As, Se, Mo(6), Cd, In, and Te; 100-fold excess of Rh, Pd, W, Bi, and Sn; 10-fold excess of Ag, Au, Pt, Hg, Os. Along with Ru(4) titrated are Ir(4), Te(3), V(5), and Ce(4). Selectivity of hydroquinone and thiourea is lower. Titrimetric procedure of determining ruthenium has been tested for ruthenium alloy containing cobalt tungsten. It cannot be recommended for analysis of the samples which dissolve in aqua regia

  19. Egg origin determination efforts

    International Nuclear Information System (INIS)

    Horvath, A.; Futo, I.; Vodila, G.; Palcsu, L.

    2012-01-01

    Complete text of publication follows. As a co-operation with the Poultry Product Board, egg and drinking water samples were received in order to investigate whether the country of origin of the egg can be determined based on its stable isotope composition with the aim of market protection of the Hungarian eggs against the mislabelled foreign ones. The scientific background is that drinking water of egg laying hens is assumed to reflect the composition of regional precipitation, and it is also an input data in the process of egg formation. In the first sampling, altogether 23 sets of egg and drinking water samples were received from different production sites covering the whole area of Hungary. The egg white samples were vacuum distilled and frozen out by liquid nitrogen at -196 deg C. The process was monitored by two vacuum gauges. Water frozen out together with the drinking water samples was measured were measured by a Thermo Finnigan Delta PLUS XP isotope ratio mass spectrometer using a GasBench II peripheral unit equipped with a GC-autosampler. As a second issue, additionally, elemental composition of egg shells were also performed for series of Hungarian, Czech and Polish egg samples by energy dispersive X-ray fluorescence. The drinking waters fit well to the Global Meteoric Water Line indicating their precipitation origin. It was experienced that the water in egg white gets enriched compared to the drinking water (Δ 18 O = -4.9 ± 1.0 per thousand and Δ D = -21.8 ± 6.4 per thousand), however, this shift is independent of the type of the hens, since the mean shifts in the eggs of Tetra and Hy-line hens are similar within error bar. For more depleted drinking water, the shift of the egg white was higher than for more enriched ones. This can be due to the contribution of the nutriment isotopic composition. The water isotope composition of the Hungarian eggs investigated was δ 18 O = -4.8 - -7.3 per thousand and δD = -46.0 - -70.7 per thousand, therefore egg

  20. Subcriticality determination of nuclear reactor

    International Nuclear Information System (INIS)

    Borisenko, V.I.; Goranchuk, V.V.; Sidoruk, N.M.; Volokh, A.F.

    2014-01-01

    In this article the subcriticality determination of nuclear reactor is considered. Emphasized that, despite the requirements of regulatory documents on the subcriticality determination of WWER from the beginning of their operation, so far, this problem has not been solved. The results of subcriticality determination of Rossi-α method of the WWER-M is presented. The possibility of subcriticality determination of WWER is considered. The possibility of subcriticality determination of Rossi-α method with time resolution is of about 100 microseconds is also considered. The possible reasons for the error in subcriticality determination of the reactor are indicated

  1. Mechanisms Governing DDK Regulation of the Initiation of DNA Replication

    Directory of Open Access Journals (Sweden)

    Larasati

    2016-12-01

    Full Text Available The budding yeast Dbf4-dependent kinase (DDK complex—comprised of cell division cycle (Cdc7 kinase and its regulatory subunit dumbbell former 4 (Dbf4—is required to trigger the initiation of DNA replication through the phosphorylation of multiple minichromosome maintenance complex subunits 2-7 (Mcm2-7. DDK is also a target of the radiation sensitive 53 (Rad53 checkpoint kinase in response to replication stress. Numerous investigations have determined mechanistic details, including the regions of Mcm2, Mcm4, and Mcm6 phosphorylated by DDK, and a number of DDK docking sites. Similarly, the way in which the Rad53 forkhead-associated 1 (FHA1 domain binds to DDK—involving both canonical and non-canonical interactions—has been elucidated. Recent work has revealed mutual promotion of DDK and synthetic lethal with dpb11-1 3 (Sld3 roles. While DDK phosphorylation of Mcm2-7 subunits facilitates their interaction with Sld3 at origins, Sld3 in turn stimulates DDK phosphorylation of Mcm2. Details of a mutually antagonistic relationship between DDK and Rap1-interacting factor 1 (Rif1 have also recently come to light. While Rif1 is able to reverse DDK-mediated Mcm2-7 complex phosphorylation by targeting the protein phosphatase glycogen 7 (Glc7 to origins, there is evidence to suggest that DDK can counteract this activity by binding to and phosphorylating Rif1.

  2. VOLTAMMETRIC DETERMINATION OF TINIDAZOLE IN ...

    African Journals Online (AJOL)

    tablet samples showed the potential applicability of the developed method for the determination of tinidazole in ... determination of TNZ in real samples like tablets, injection, urine and biological fluids [24-27]. Almost all ..... during the storage.

  3. Determinant of Poverty in Ethiopia

    African Journals Online (AJOL)

    preferred customer

    a logistic regression model to identify determinants of wellbeing of the household ... interest of researchers, public authorities and international organizations. The ... have to understand the determinants of poverty in rural and urban Ethiopia.

  4. Reduction and determination of dixanthogens.

    Science.gov (United States)

    Prasad, M S

    1971-06-01

    A convenient method for the reduction and determination of dixaathogen has been developed. It is based on the quantitative reaction of dixanthogen with zinc amalgam to form xanthate; the latter can be determined by iodine titration, potentiometric titration with silver nitrate or by spectrophotometry at 310 mmu. Dixanthogen can be determined in mixtures containing xanthate, by titration of aliquots with and without reduction. Higher dixanthogens can also be determined, and flotation liquors analysed.

  5. Investigations on radiosensitive and radioresistant populations of Drosophila melanogaster. Pt. 12

    International Nuclear Information System (INIS)

    Noethel, H.

    1981-01-01

    In earlier studies the recessive genetic factor rar-3 (3 - 49.8) of Drosophila melanogaster had been found to reduce the sensitivity of immature oocytes to the mutagenic action of X-rays. The present work was devoted to an extension of these studies to other germ-cell stages in both male and female and also somatic cells. The results show that, in the female, the effects of rar-3 are manifest in all germ-cell stages including gonia and nurse cells but not in mature oocytes. In the male germ-cell stages, rar-3 was without any measurable effect; maternal-effect studies were likewise negative. Somatic tissues were also unaffected. Furthermore, rar-3 was apparently not active in larval oogonia. It is therefore concluded that the activity of rar-3 is switched on in oogonia during puparium formation or metamorphosis and persists until before the formation of the mature oocyte. (orig.)

  6. Detection of DNA strand breaks in mammalian cells using the radioresistant bacterium PprA protein

    International Nuclear Information System (INIS)

    Satoh, Katsuya; Wada, Seiichi; Narumi, Issay; Kikuchi, Masahiro; Funayama, Tomoo; Kobayashi, Yasuhiko

    2003-01-01

    We have previously found that the PprA protein from Deinococcus radiodurans possesses ability to recognize DNA carrying strand breaks. In the present study, we attempted to visualize radiation-induced DNA strand breaks with PprA protein using immunofluorescence technique to elucidate the DNA damage response mechanism in mammalian cultured cells. As a result, colocalization of Cy2 and DAPI fluorescent signals was observed. This observation suggests that DNA strand breaks in the nucleus of CHO-K1 cells were effectively detected using the PprA protein. The amount of DNA strand breaks (integrated density of Cy2 fluorescent signals) was increased with the increase in the radiation dose. (author)

  7. PprA, a pleiotropic protein for radioresistance, works through DNA ...

    Indian Academy of Sciences (India)

    GFP-PprA fusion was subcultured in fresh TYG medium containing spectinomycin (75 .... action on the damaged site in the genome. These results sug- gested that ... toroidal structure, which once upon a time was thought to be the basis for its ...

  8. Radioresistance of experimentally-produced hybrid of Indian spinach (Beta palonga Basu and Mukherjee)

    International Nuclear Information System (INIS)

    Mukherjee, K.K.; Basu, R.K.

    1975-01-01

    An experimentally-produced hybrid between red and green plants of Beta palonga and the segregating population in F 2 showed more resistance to acute X-irradiation of seed than did their parents, as measured by seed germination, plant height, abnormal plant growth, chromosomal abnormality during meiosis and pollen grain sterility. In every measurement the F 2 plants were more sensitive than the F 1 hybrid. The radiosensitivity could not be interpreted in terms of average interphase chromosome volume. The resistance of the hybrid is suggested to be due to factors associated with heterozygosity and heterosis, although this has not been definately established. (author)

  9. Delayed Growth Suppression and Radioresistance Induced by Long-Term Continuous Gamma Irradiation.

    Science.gov (United States)

    Nakajima, Hiroo; Furukawa, Chiharu; Chang, Young-Chae; Ogata, Hiromitsu; Magae, Junji

    2017-08-01

    Biological response to ionizing radiation depends not only on the type of radiation and dose, but also on the duration and dose rate of treatment. For a given radiation dose, the biological response may differ based on duration and dose rate. We studied the properties of two human cell lines, M059K glioma and U2OS osteosarcoma, continuously exposed to γ rays for long time periods of more than five months. Growth inhibition in both cell lines was dependent on total dose when exposed to acute radiation over several minutes, whereas prolonged growth inhibition was dependent on dose rate after continuous irradiation over several months. The minimum dose rate for growth inhibition was 53.6 mGy/h. Cell cycle analysis showed G 1 phase accumulation in cell populations continuously exposed to γ rays, and G 2 phase accumulation in cells acutely exposed to high-dose-rate γ rays. Cells continuously exposed to γ rays continued to exhibit delayed growth suppression even after one month in an environment of background radiation, and maintained a high-level expression of c-Jun and its phosphorylation forms, as well as resistance to apoptosis induced by staurosporine and chemotherapeutic agents. These delayed effects were not observed in cells acutely exposed to 5 Gy of radiation. These results suggest that optimization of the irradiation schedule is crucial for risk estimation, protection and therapeutic utilization of ionizing radiation.

  10. Crypt base columnar stem cells in small intestines of mice are radioresistant

    NARCIS (Netherlands)

    Hua, G.; Thin, T.H.; Feldman, R.; Haimovitz-Friedman, A.; Clevers, H.; Fuks, Z.; Kolesnick, R.

    2012-01-01

    BACKGROUND & AIMS: Adult stem cells have been proposed to be quiescent and radiation resistant, repairing DNA double-strand breaks by nonhomologous end joining. However, the population of putative small intestinal stem cells (ISCs) at position +4 from the crypt base contradicts this model, in that

  11. Clinical study of combined radio-thermotherapy for radioresistant tumors, 1

    International Nuclear Information System (INIS)

    Hiraoka, Masahiro; Ri, Nariyoshi; Ono, Kouji; Nishidai, Takehiro; Takahashi, Masaji

    1981-01-01

    Seventeen cases of superficial malignant tumors considered to be refractory to conventional treatment modalities were treated by thermotherapy in combination with radiation. Heat was generated by a microwave apparatus of 2450MHz. Fourteen cases which received complete thermotherapy were analysed and the following results were obtained. 1. Intratumor temperature of over 41 0 C was obtained in all cases and temperature of over 42.5 0 C was achieved in ten cases (71%). 2. In five out of fourteen cases, both intratumor and adjacent normal tissue temperatures were measured and intratumor temperature was approximately 1 0 C higher on the average than normal tissue temperature. 3. Phantom and clinical examinations demonstrated that effective heating depth obtained by this apparatus was approximately 3 cm from the surface. 4. Of eleven cases who hadn't received any radiotherapy, five cases showed complete regression (46%), three cases partial regression (27%) and no regression was observed in three cases (27%). Of three cases who had received full course of radiotherapy, two cases showed partial regression (67%) and one demonstrated no regression (33%). It was concluded that this heating unit was applicable to the thermotherapy for superficial malignant tumors. Radiosensitizing effect of heat was suggested, however more clinical experiences are needed to evaluate the definite usefulness of this treatment. (author)

  12. Neuroendorine differentiation in prostate cancer: A mechanism of radioresistance and treatment failure

    Directory of Open Access Journals (Sweden)

    Chang-Deng eHu

    2015-04-01

    Full Text Available Neuroendocrine differentiation (NED in prostate cancer is a well recognized phenotypic change by which prostate cancer cells transdifferentiate into neuroendocrine-like (NE-like cells. NE-like cells lack the expression of androgen receptor and prostate specific antigen, and are resistant to treatments. In addition, NE-like cells secrete peptide hormones and growth factors to support the growth of surrounding tumor cells in a paracrine manner. Accumulated evidence has suggested that NED is associated with disease progression and poor prognosis. The importance of NED in prostate cancer progression and therapeutic response is further supported by the fact that therapeutic agents, including androgen deprivation therapy, chemotherapeutic agents, and radiotherapy, also induce NED. We will review the work supporting the overall hypothesis that therapy-induced NED is a mechanism of resistance to treatments, as well as discuss the relationship between therapy-induced NED and therapy-induced senescence, epithelial-to-mesenchymal transition, and cancer stem cells. Furthermore, we will use radiation-induced NED as a model to explore several NED-based targeting strategies for development of novel therapeutics. Finally, we propose future studies that will specifically address therapy-induced NED in the hope that a better treatment regimen for prostate cancer can be developed.

  13. Gene fusions with lacZ by duplication insertion in the radioresistant bacterium Deinococcus radiodurans

    International Nuclear Information System (INIS)

    Lennon, E.; Minton, K.W.

    1990-01-01

    Deinococcus radiodurans is the most-studied species of a eubacterial family characterized by extreme resistance to DNA damage. We have focused on developing molecular biological techniques to investigate the genetics of this organism. We report construction of lacZ gene fusions by a method involving both in vitro splicing and the natural transformation of D. radiodurans. Numerous fusion strains were identified by expression of beta-galactosidase. Among these fusion strains, several were inducible by exposure to the DNA-damaging agent mitomycin C, and four of the inducible fusion constructs were cloned in Escherichia coli. Hybridization studies indicate that one of the damage-inducible genes contains a sequence reiterated throughout the D. radiodurans chromosome. Survival measurements show that two of the fusion strains have increased sensitivity to mitomycin C, suggesting that the fusions within these strains inactivate repair functions

  14. Intracellular thiol levels and radioresistance: Studies with glutathione and glutathione mono ethyl ester

    International Nuclear Information System (INIS)

    Astor, M.B.; Meister, A.; Anderson, M.E.

    1987-01-01

    Intracellular thiols such as glutathione (GSH) protect cells against free radicals formed during oxidative metabolism or from exposure to drugs or ionizing radiation. The role of intracellular GSH in the repair of radiation induced free radical damage was studied using GSH or its analog glutathione mono ethyl ester (GEE), which readily penetrates into the cell. Chinese hamster V79 cells with normal GSH levels were afforded equal protection under aerated and hypoxic conditions (DMF = 1.2 OER = 3.7) by both 10 mM GSH and GEE although GEE had raised interacellular GSH levels three-fold. Growth of V79 cells in cysteine free media resulted in undetectable levels of GSH and OER of 2.2 with no change in aerated survival. Restoration of intracellular GSH by 10 mM GEE resulted in an increase of the OER from 2.2. to 3.8 (DMF = 1.7). Only 14% of the intracellular GSH needs to be repleted to give an OER of 3.0. These experiments provide evidence that thiols do play a role in the oxygen effect and are present at levels in excess of what is necessary for maximal radioprotection

  15. Radiation-induced nitric oxide mitigates tumor hypoxia and radioresistance in a murine SCCVII tumor model

    International Nuclear Information System (INIS)

    Nagane, Masaki; Yasui, Hironobu; Yamamori, Tohru; Zhao, Songji; Kuge, Yuji; Tamaki, Nagara; Kameya, Hiromi; Nakamura, Hideo; Fujii, Hirotada; Inanami, Osamu

    2013-01-01

    Highlights: •IR-induced NO increased tissue perfusion and pO 2 . •IR increased NO production in tumors without changes in the mRNA and protein levels of NOS isoforms. •NOS activity assay showed that IR upregulated eNOS activity in tumors. •IR-induced NO decreased tumor hypoxia and altered tumor radiosensitivity. -- Abstract: Tumor hypoxia, which occurs mainly as a result of inadequate tissue perfusion in solid tumors, is a well-known challenge for successful radiotherapy. Recent evidence suggests that ionizing radiation (IR) upregulates nitric oxide (NO) production and that IR-induced NO has the potential to increase intratumoral circulation. However, the kinetics of NO production and the responsible isoforms for NO synthase in tumors exposed to IR remain unclear. In this study, we aimed to elucidate the mechanism by which IR stimulates NO production in tumors and the effect of IR-induced NO on tumor radiosensitivity. Hoechst33342 perfusion assay and electron spin resonance oxymetry showed that IR increased tissue perfusion and pO 2 in tumor tissue. Immunohistochemical analysis using two different hypoxic probes showed that IR decreased hypoxic regions in tumors; treatment with a nitric oxide synthase (NOS) inhibitor, L-NAME, abrogated the effects of IR. Moreover, IR increased endothelial NOS (eNOS) activity without affecting its mRNA or protein expression levels in SCCVII-transplanted tumors. Tumor growth delay assay showed that L-NAME decreased the anti-tumor effect of fractionated radiation (10 Gy × 2). These results suggested that IR increased eNOS activity and subsequent tissue perfusion in tumors. Increases in intratumoral circulation simultaneously decreased tumor hypoxia. As a result, IR-induced NO increased tumor radiosensitivity. Our study provides a new insight into the NO-dependent mechanism for efficient fractionated radiotherapy

  16. Relative radioresistance of xenogeneic and hybrid resistance to bone marrow transplantation

    International Nuclear Information System (INIS)

    Rauchwerger, J.M.; Gallagher, M.T.; Monie, H.J.; Trentin, J.J.

    1977-01-01

    Following a single exposure to 1,100 R whole-body irradiation, (C57Bl/6 x A)F 1 hybrid mice were genetically resistant to transplantation of 5 x 10 5 C57 parental bone marrow cells (hybrid resistance). Hybrid resistance was minimally broken by increasing the radiation exposure to 2,200 R, and maximally broken by increasing it to 5,000 R. Following 1,100 R, (C57Bl/6 x A)F 1 hybrid mice were genetically resistant to transplantation of 5 x 10 6 Lewis RBM cells (xenogeneic resistance). This xenogeneic resistance was not even minimally broken following 5,000 R, but was broken following 6,600 R. With different doses of parental or xenogeneic marrow cells, it was found that the amount of irradiation exposure required to break either hybrid resistance or xenogeneic resistance was inversely proportional to the dose of bone marrow cells used

  17. BEMER Electromagnetic Field Therapy Reduces Cancer Cell Radioresistance by Enhanced ROS Formation and Induced DNA Damage.

    Directory of Open Access Journals (Sweden)

    Katja Storch

    Full Text Available Each year more than 450,000 Germans are expected to be diagnosed with cancer subsequently receiving standard multimodal therapies including surgery, chemotherapy and radiotherapy. On top, molecular-targeted agents are increasingly administered. Owing to intrinsic and acquired resistance to these therapeutic approaches, both the better molecular understanding of tumor biology and the consideration of alternative and complementary therapeutic support are warranted and open up broader and novel possibilities for therapy personalization. Particularly the latter is underpinned by the increasing utilization of non-invasive complementary and alternative medicine by the population. One investigated approach is the application of low-dose electromagnetic fields (EMF to modulate cellular processes. A particular system is the BEMER therapy as a Physical Vascular Therapy for which a normalization of the microcirculation has been demonstrated by a low-frequency, pulsed EMF pattern. Open remains whether this EMF pattern impacts on cancer cell survival upon treatment with radiotherapy, chemotherapy and the molecular-targeted agent Cetuximab inhibiting the epidermal growth factor receptor. Using more physiological, three-dimensional, matrix-based cell culture models and cancer cell lines originating from lung, head and neck, colorectal and pancreas, we show significant changes in distinct intermediates of the glycolysis and tricarboxylic acid cycle pathways and enhanced cancer cell radiosensitization associated with increased DNA double strand break numbers and higher levels of reactive oxygen species upon BEMER treatment relative to controls. Intriguingly, exposure of cells to the BEMER EMF pattern failed to result in sensitization to chemotherapy and Cetuximab. Further studies are necessary to better understand the mechanisms underlying the cellular alterations induced by the BEMER EMF pattern and to clarify the application areas for human disease.

  18. Caveolin-1 mediated radioresistance of 3D grown pancreatic cancer cells

    International Nuclear Information System (INIS)

    Hehlgans, Stephanie; Eke, Iris; Storch, Katja; Haase, Michael; Baretton, Gustavo B.; Cordes, Nils

    2009-01-01

    Background and purpose: Resistance of pancreatic ductal adenocarcinoma (PDAC) to chemo- and radiotherapy is a major obstacle. The integral membrane protein Caveolin-1 (Cav-1) has been suggested as a potent target in human pancreatic carcinoma cells. Materials and methods: Human pancreatic tumor cells were examined in a three-dimensional (3D) cell culture model with regard to clonogenic survival, apoptosis, radiogenic DNA-double strand breaks and protein expression and phosphorylation under siRNA-mediated knockdown of Cav-1 without and in combination with irradiation (X-rays, 0-6 Gy). Immunohistochemistry was used to assess Cav-1 expression in biopsies from patients with PDAC. Results: Tumor cells in PDAC showed significantly higher Cav-1 expression relative to tumor stroma. Cav-1 knockdown significantly reduced β1 integrin expression and Akt phosphorylation, induced Caspase 3- and Caspase 8-dependent apoptosis and enhanced the radiosensitivity of 3D cell cultures. While cell cycling and Cav-1 promoter activity remained stable, Cav-1 knockdown-induced radiosensitization correlated with elevated numbers of residual DNA-double strand breaks. Conclusions: Our data strongly support the concept of Cav-1 as a potent target in pancreatic carcinoma cells due to radiosensitization and Cav-1 overexpression in tumor cells of PDAC. 3D cell cultures are powerful and useful tools for the testing of novel targeting strategies to optimize conventional radio- and chemotherapy regimes for PDAC.

  19. Brain Tumor’s Radioresistance: The Neighborhood Helps | Center for Cancer Research

    Science.gov (United States)

    Glioblastoma (GBM) is the most common and most aggressive form of brain cancer. The primary treatment for GBM is radiation therapy. Unfortunately, while some patients initially respond, the vast majority of GBM patients fail radiotherapy, and the tumor usually grows back within two years. To gain a better understanding of the biological basis for GBM resistance to radiation, researchers initially studied GBM cell lines in vitro. In recent years, the focus has been on so-called tumor stem-like cells (TSCs), which are thought to be responsible for driving and maintaining tumor growth. To the researchers’ surprise, TSCs grown in vitro did not have the same ability to resist radiation as TSCs in the GBM tumors.

  20. Determinants

    Directory of Open Access Journals (Sweden)

    N. Ntui Asundep

    2013-12-01

    Nineteen percent of the women experienced an adverse pregnancy outcome. For 49% of the women, cost influenced their antenatal attendance. Cost was associated with increased likelihood of a woman experiencing an adverse outcome (adjusted OR = 2.15; 95% CI = 1.16–3.99; p = 0.016. Also, women with >5 births had an increased likelihood of an adverse outcome compared with women with single deliveries (adjusted OR = 3.77; 95% CI = 1.50–9.53; p = 0.005. The prevalence of adverse outcomes was lower than previously reported (44.6 versus 19%. Cost and distance were associated with adverse outcomes after adjusting for confounders. Cost and distance could be minimized through a wider application of the Ghana National Health Insurance Scheme.

  1. Determination of cadmium selenide nonstoichiometry

    International Nuclear Information System (INIS)

    Brezhnev, V.Yu.; Kharif, Ya.L.; Kovtunenko, P.V.

    1986-01-01

    Physicochemical method of determination of cadmium selenide nonstoichiometry is developed. The method nature consists in the fact, that under definite conditions dissolved cadmium is extracted from crystals to a vapor phase and then is determined in it using the photocolorimetric method. Cadmium solubility in CdSe crystal is calculated from known CdSe mass and amount of separated cadmium. The lower boundary of determined contents constitutes 1x10 -5 % mol at sample of cadmium selenide 10 g

  2. Power, Ideology, and Technological Determinism

    Directory of Open Access Journals (Sweden)

    David J. Hess

    2015-12-01

    Full Text Available A Commentary on Taylor Dotson’s “Technological Determinism and Permissionless Innovation as Technocratic Governing Mentalities: Psychocultural Barriers to the Democratization of Technology”

  3. Dietary Determinants of Prostate Cancer

    National Research Council Canada - National Science Library

    Chu, Lisa W

    2005-01-01

    .... Epidemiologic studies suggest that dietary factors may be important in the etiology of PCa. The objective of our research is to determine how nutritional compounds genistein, betasitosterol (STT...

  4. Teaching Determinants Using Rook Arrangements

    Science.gov (United States)

    Hendrickson, Anders O. F.

    2018-01-01

    Teaching determinants poses significant challenges to the instructor of a proof-based undergraduate linear algebra course. The standard definition by cofactor expansion is ugly, lacks symmetry, and is hard for students to use in proofs. We introduce a visual definition of the determinant that interprets permutations as arrangements of…

  5. Uranium hexafluoride. Bromine spectrophotometric determination

    International Nuclear Information System (INIS)

    Anon.

    Bromine determination in hydrolized uranium hexafluoride by reduction of bromates by ferrous sulfate, oxidation of bromides by potassium permanganate to give bromine which is extracted into carbon tetrachloride and transformed in eosine for spectrophotometry at 510 nm. The method is suitable for determining 5 to 150 ppm with respect to uranium [fr

  6. The Determinants of Food Choice

    DEFF Research Database (Denmark)

    Leng, Gareth; Adan, Roger A. H.; Belot, Michele

    2017-01-01

    , we need to be able to make valid predictions about the consequences of proposed interventions, and for this, we need a better understanding of the determinants of food choice. These determinants include dietary components (e.g. highly palatable foods and alcohol), but also diverse cultural and social...

  7. Self-Determination after Kosovo

    DEFF Research Database (Denmark)

    Wolff, Stefan; Rodt, Annemarie Peen

    2013-01-01

    This article discusses the meaning of self-determination in its historical and contemporary contexts and examines the different options available for the accommodation of contested self-determination claims. Among these, the creation of a new state, arguably, is the most radical of options and on...

  8. Boundary determinations for trivariate solids

    International Nuclear Information System (INIS)

    Duchaineau, M; Joy, K I

    1999-01-01

    The trivariate tensor-product B-spline solid is a direct extension of the B-spline patch and has been shown to be useful in the creation and visualization of free-form geometric solids. Visualizing these solid objects requires the determination of the boundary surface of the solid, which is a combination of parametric and implicit surfaces. This paper presents a method that determines the implicit boundary surface by examination of the Jacobian determinant of the defining B-spline function. Using an approximation to this determinant, the domain space is adaptively subdivided until a mesh can be determined such that the boundary surface is close to linear in the cells of the mesh. A variation of the marching cubes algorithm is then used to draw the surface. Interval approximation techniques are used to approximate the Jacobian determinant and to approximate the Jacobian determinant gradient for use in the adaptive subdivision methods. This technique can be used to create free-form solid objects, useful in geometric modeling applications

  9. Immunological methods for gentamicin determination

    International Nuclear Information System (INIS)

    Krugers Dagneauz, P.G.L.C.; Olthuis, F.M.F.G.

    1979-01-01

    For immunoassay, an antibody against the substance to the determined, the pure substance itself, and a labelled form or derivative of the substance are required. The principles and problems of the preparation of antibodies are discussed, some methods for the preparation of derivatives labelled with radioactive tracers or enzymes are reviewed, and homologous enzyme-immunological determination of gentamicin is discussed in detail. A comparison is mae of three radio-immunological determination methods, and the most suitable radio-immunological method is compared with two microbiological techniques. The results are found to be comparable. (Auth.)

  10. Determinants of Homeownership in Denmark

    DEFF Research Database (Denmark)

    Lauridsen, Jørgen T.; Skak, Morten

    . The paper adds to earlier papers by the same authors where determinants of the homeownership rate were found using (average) data for 270 Danish municipalities. By using data directly related to individual households whose inhabitants have chosen to be or not to be homeowners, the analysis reveals...... characteristics and restrictions that influence the choice between renting and ownership. Among the determinants investigated is civil and social status of the breadwinner and various household characteristics including income. The empirical results generally suggest that the impact of the determinants...

  11. Age determination and geological studies

    International Nuclear Information System (INIS)

    Stevens, R.D.; Delabio, R.N.; Lachance, G.R.

    1982-01-01

    Two hundred and eight potassium-argon age determinations carried out on Canadian rocks and minerals are reported. Each age determination is accompanied by a description of the rock and mineral concentrate used; brief interpretative comments regarding the geological significance of each age are also provided where possible. The experimental procedures employed are described in brief outline and the constants used in the calculation of ages are listed. Two geological time-scales are reproduced in tabular form for ready reference and an index of all Geological Survey of Canada K-Ar age determinations published in this format has been prepared using NTS quadrangles as the primary reference

  12. Network mapping and usage determination

    CSIR Research Space (South Africa)

    Senekal, FP

    2007-07-01

    Full Text Available detection. Based on this information, topology determination techniques can be applied to infer network structure from the information. Techniques to visualise the information are discussed. IP geolocation (the ability to associate a geographical coordinate...

  13. Differential spectrophotometric determination of plutonium

    International Nuclear Information System (INIS)

    Lecat, J.

    1980-01-01

    Differential spectrophotometric method is used for determination of plutonium reduced to oxydation state III+ by ascorbic acid, at 560 nm. Concentration of solutions is 4 g/l and accuracy of the method is better than 0,3% [fr

  14. Sodium sampling and impurities determination

    International Nuclear Information System (INIS)

    Docekal, J.; Kovar, C.; Stuchlik, S.

    1980-01-01

    Samples may be obtained from tubes in-built in the sodium facility and further processed or they are taken into crucibles, stored and processed later. Another sampling method is a method involving vacuum distillation of sodium, thus concentrating impurities. Oxygen is determined by malgamation, distillation or vanadium balance methods. Hydrogen is determined by the metal diaphragm extraction, direct extraction or amalgamation methods. Carbon is determined using dry techniques involving burning a sodium sample at 1100 degC or using wet techniques by dissolving the sample with an acid. Trace amounts of metal impurities are determined after dissolving sodium in ethanol. The trace metals are concentrated and sodium excess is removed. (M.S.)

  15. Determination of multiple scattering effects

    International Nuclear Information System (INIS)

    Langevin, M.

    1981-01-01

    The integration of Sigmund and Winterbon numerical values is extended to the reduced thickness tau=2000. The diagram obtained allows a simple determination of the multiple scattering effect for different targets and projectiles [fr

  16. Refugee status determination: three challenges

    Directory of Open Access Journals (Sweden)

    Martin Jones

    2009-04-01

    Full Text Available Refugee status determination (RSD, which is vital to the protection of so many asylum seekers worldwide, is at best an imperfect, haphazard and challenging process. It merits greater attention and appropriate reform.

  17. Diagnostic agent for radioimmunological determinations

    International Nuclear Information System (INIS)

    Updike, S.J.

    1978-01-01

    The invention concerns a diagnostic agent for radioimmunological determinations. According to the invention, a binding protein (protein globulins, antibodies) of an aqueous solution specific for the substance to be determined is incorporated in gel particles of a strongly hydrophilic insoluble gel of controlled pore size. After subsequent drying of the system, a radioactively labelled form of the substance to be determined from a non-aqueous medium is included. The mixture is dried again. The diagnostic agent forred can be well stored and is very stable. There is no loss of activity of the specific bonding protein when drying according to the invented method. The described reagent can be effectively applied to the determination of many antigens and haptens: The gel is rehydrated by the sample to be investigated; as a result of this, the non-bonded tracer is set free and competes with the non-labelled substance for the bonding position. (VJ) [de

  18. Radioimmunological determination of 25-hydroxycholecalciferol

    International Nuclear Information System (INIS)

    Gmeiner, M.

    1976-01-01

    The antibody to vitamin D 3 as hapten proved useful in determination of 25-hydroxycalciferol (25-OH-CC). The attempt also to determine vitamin D 3 directly with the aid of this radioimmunological procedure failed because of the poor solubility of the vitamin in aqueous systems. Because of the linkage to the C3 the D-ring and C17 side chain would be expected to be the immunodeterminant sites. Although the antibody can be used to determine 25-OH-CC, there is no cross-reaction with cholesterol. This indicates the importance of the open B-ring of this vitamin. Scruting of the method showed good reproducibility and accuracy. The most favorable evaluation region is 0.1-2 ng/250μl sample. The procedure described enables 25-hydroxy vitamin D 3 to be determined without previous purification of the sample extract. (author)

  19. Sample size determination and power

    CERN Document Server

    Ryan, Thomas P, Jr

    2013-01-01

    THOMAS P. RYAN, PhD, teaches online advanced statistics courses for Northwestern University and The Institute for Statistics Education in sample size determination, design of experiments, engineering statistics, and regression analysis.

  20. Star trackers for attitude determination

    DEFF Research Database (Denmark)

    Liebe, Carl Christian

    1995-01-01

    One problem comes to all spacecrafts using vector information. That is the problem of determining the attitude. This paper describes how the area of attitude determination instruments has evolved from simple pointing devices into the latest technology, which determines the attitude by utilizing...... a CCD camera and a powerful microcomputer. The instruments are called star trackers and they are capable of determining the attitude with an accuracy better than 1 arcsecond. The concept of the star tracker is explained. The obtainable accuracy is calculated, the numbers of stars to be included...... in the star catalogue are discussed and the acquisition of the initial attitude is explained. Finally the commercial market for star trackers is discussed...

  1. Selenium determination by fluorimetric method

    International Nuclear Information System (INIS)

    Lavorenti, A.

    1981-01-01

    A fluorimetric method to determine selenium both in vegetable samples and blood serum is developed. The method consists of a radioisotope 75 Se initially in order to optimize the determination of analytical conditions. Three samples digestion processes and also some factors related to methodology is studied. The nitric-percloric digestion process for 40 samples and the analytical process is shown. (M.J.C.) [pt

  2. Determinants of Aggressive Tax Avoidance

    OpenAIRE

    Herbert, Tanja

    2015-01-01

    This thesis consists of three essays examining determinants of aggressive tax avoidance. The first essay “Measuring the Aggressive Part of International Tax Avoidance”, co-authored with Prof. Dr. Michael Overesch, proposes a new measure that isolates the additional or even aggressive part in international tax avoidance and analyzes the determinants of aggressive tax avoidance of multinational enterprises. The second essay “Capital Injections and Aggressive Tax Planning - Can Banks Have It All...

  3. Determination of the scattering amplitude

    International Nuclear Information System (INIS)

    Gangal, A.D.; Kupsch, J.

    1984-01-01

    The problem to determine the elastic scattering amplitude from the differential cross-section by the unitarity equation is reexamined. We prove that the solution is unique and can be determined by a convergent iteration if the parameter lambda=sin μ of Newton and Martin is bounded by lambda 2 approx.=0.86. The method is based on a fixed point theorem for holomorphic mappings in a complex Banach space. (orig.)

  4. Modern methods for radiostrontium determination

    International Nuclear Information System (INIS)

    Grahek, Z.; Kosutic, K.; Lulic, S.

    1998-01-01

    The basic principles of the ion exchange chromatographic determination of radioactive strontium in liquid wastes and natural samples are presented. The sample is inserted into the chromatographic column through the injection system connected to a pump. Strontium is separated by column elution. A flow scintillation beta detector is positioned at the column outlet. Prior to entering the column, strontium is mixed with a scintillator. The apparatus for semi-automatic radiostrontium determination is also described. (M.D.)

  5. The Determinants of Debt Financing

    OpenAIRE

    Zhao, Chenkai

    2013-01-01

    Debt financing is an important part in capital structure. Over the fifty years, most scholars and researchers focus primarily on the balance between debt financing and equity financing. And only few research involve in types of debt financing, as well as the determinant of debt financing. This study is aim to analyse the determinate of debt financing, which examine that the influence by eight different elements. This dissertation examined by quantitative techniques with 591 UK listed comp...

  6. Football performance and its determinants

    OpenAIRE

    Macháček, Martin

    2017-01-01

    This thesis focuses on enumeration of the essential psychosocial determinants affecting performance of the footballers. These determinants are divided into three sections. Personality of athlete as a key factor influencing his performance is discussed in the chapter one. Social and cultural environment are the subjects of the second chapter. Specifics and partial aspects of sports environments are presented in the third chapter. Definition of performance in football and the possibility of its...

  7. Determination of plutonium in environment

    International Nuclear Information System (INIS)

    Sakanoue, Masanobu

    1978-01-01

    Past and present methods of determining the amount of plutonium in the environment are summarized. Determination of the amount of plutonium in uranium ore began in 1941. Plutonium present in polluted environments due to nuclear explosions, nuclear power stations, etc. was measured in soil and sand in Nagasaki in 1951 and in ash in Bikini in 1954. Analytical methods of measuring the least amount of plutonium in the environment were developed twenty years later. Many studies on and reviews of these methods have been reported all over the world, and a standard analytical procedure has been adopted. A basic analytical method of measurement was drafted in Japan in 1976. The yield, treatment of samples, dissolution, separation, control of measurable ray sources determination by α spectrometry, cross-check determination, and treatment of samples containing hardly soluble plutonium were examined. At present, the amount of plutonium can be determined by all of these methods. The presence of plutonium was studied further, and the usefulness of determination of the plutonium isotope ratio is discussed. (Kumagai, S.)

  8. The Determining Finite Automata Process

    Directory of Open Access Journals (Sweden)

    M. S. Vinogradova

    2017-01-01

    Full Text Available The theory of formal languages widely uses finite state automata both in implementation of automata-based approach to programming, and in synthesis of logical control algorithms.To ensure unambiguous operation of the algorithms, the synthesized finite state automata must be deterministic. Within the approach to the synthesis of the mobile robot controls, for example, based on the theory of formal languages, there are problems concerning the construction of various finite automata, but such finite automata, as a rule, will not be deterministic. The algorithm of determinization can be applied to the finite automata, as specified, in various ways. The basic ideas of the algorithm of determinization can be most simply explained using the representations of a finite automaton in the form of a weighted directed graph.The paper deals with finite automata represented as weighted directed graphs, and discusses in detail the procedure for determining the finite automata represented in this way. Gives a detailed description of the algorithm for determining finite automata. A large number of examples illustrate a capability of the determinization algorithm.

  9. A Predictive Framework for Determining How Journalists Determine News.

    Science.gov (United States)

    Gaudino, James L.

    To determine how to articulate a concrete definition of the substance of the journalist's occupation, this paper offers a propositional framework of news value based on Kurt Lewin's gatekeeper model. First, the paper follows the established suggestion that news decisions are best studied from a gatekeeping perspective or that "news is…

  10. Methods of humidity determination Part II: Determination of material humidity

    OpenAIRE

    Rübner, Katrin; Balköse, Devrim; Robens, E.

    2008-01-01

    Part II covers the most common methods of measuring the humidity of solid material. State of water near solid surfaces, gravimetric measurement of material humidity, measurement of water sorption isotherms, chemical methods for determination of water content, measurement of material humidity via the gas phase, standardisation, cosmonautical observations are reviewed.

  11. Protein determination in single corns

    International Nuclear Information System (INIS)

    Knorr, J.; Schiekel, M.; Franke, W.; Focke, F.

    1994-01-01

    Determination of protein content in food materials is usually done by analyzing the nitrogen amount by wet chemical Kjeldahl method. An improved accuracy accompanied by smaller analyzing intervals can be achieved using nondestructive neutron activation. Analyses have been performed using 14 MeV neutrons to determine the content of N and P in single wheat corns. Irradiation parameters have been optimized to prevent serious radiation damage in grains. About 200 single corns have been investigated with total net weights ranging from 30 to 70 mg. The tested arrangement allows determination of nitrogen amount in a single corn down to 0.3 mg with an accuracy of better than 4 %. Mean nitrogen concentrations in the range from 9 to 19% per corn have been detected. (author) 5 refs.; 6 figs

  12. Structural determination of organic compounds

    International Nuclear Information System (INIS)

    Kintzinger, J.P.

    1991-01-01

    This paper reports that the current methods available in high-field NMR spectroscopy are such that the tridimensional structure determination of any rigid molecule containing only carbon and hydrogen atoms may be achieved. The connectivities between carbon-carbon, carbon-hydrogen, and hydrogen-hydrogen atoms are determined by multipulse and two-dimensional (2D) experiments. These connectivity patterns or maps allow a step-by-step reconstruction of the molecular structures. From the carbon-carbon connectivity map, the carbon framework of the molecule is obtained, whereas the carbon-hydrogen pattern allows determination of the positions of the hydrogen atoms on their corresponding carbon atoms. High-field spectrometers are then necessary to remove fortuitous degeneracy and to reduce the proton spectra to a nearly first-order one, allowing an easy measurement of the chemical shifts and the coupling constants

  13. Determining distances using asteroseismic methods

    DEFF Research Database (Denmark)

    Aguirre, Victor Silva; Casagrande, L.; Basu, Sarbina

    2013-01-01

    Asteroseismology has been extremely successful in determining the properties of stars in different evolutionary stages with a remarkable level of precision. However, to fully exploit its potential, robust methods for estimating stellar parameters are required and independent verification of the r......Asteroseismology has been extremely successful in determining the properties of stars in different evolutionary stages with a remarkable level of precision. However, to fully exploit its potential, robust methods for estimating stellar parameters are required and independent verification...... fluxes, and thus distances for field stars in a self-consistent manner. Applying our method to a sample of solar-like oscillators in the {\\it Kepler} field that have accurate {\\it Hipparcos} parallaxes, we find agreement in our distance determinations to better than 5%. Comparison with measurements...

  14. Method of molybdenum kinetic determination

    International Nuclear Information System (INIS)

    Krejngol'd, S.U.; Dzotsenidze, N.E.; Ruseishviyai, T.G.; Nelen', I.M.

    1980-01-01

    The method molybdenum kinetic determination according to oxidation of pyrogallol with bromate in the medium of 0.05-0.15 M perchloric or sulphuric acids is presented. 1 mg of Ni, Co, Mn, Mg, Zn, Cr(3); 100 μg of Ca, Al, Cu, 10 μg of Cr(4), W; 10 μg of Fe in the presence of 22x10 - 4 M solution of EDTA, as well as 10 - 4 M solutions of chlorides and fluorides, 10 - 5 M solutions of bromides do not interfere with molybdenum determination using the given method. The method is rather simple, it takes 30 min to carry out the analysis. Determination limit of molybdenum constitutes 0.01 μg/ml

  15. Lessons for Inductive Germline Determination

    Science.gov (United States)

    Seervai, Riyad N.H.; Wessel, Gary M.

    2015-01-01

    SUMMARY Formation of the germline in an embryo marks a fresh round of reproductive potential, yet the developmental stage and location within the embryo where the primordial germ cells (PGCs) form differs wildly among species. In most animals, the germline is formed either by an inherited mechanism, in which maternal provisions within the oocyte drive localized germ-cell fate once acquired in the embryo, or an inductive mechanism that involves signaling between cells that directs germ-cell fate. The inherited mechanism has been widely studied in model organisms such as Drosophila melanogaster, Caenorhabditis elegans, Xenopus laevis, and Danio rerio. Given the rapid generation time and the effective adaptation for laboratory research of these organisms, it is not coincidental that research on these organisms has led the field in elucidating mechanisms for germline specification. The inductive mechanism, however, is less well understood and is studied primarily in the mouse (Mus musculus). In this review, we compare and contrast these two fundamental mechanisms for germline determination, beginning with the key molecular determinants that play a role in the formation of germ cells across all animal taxa. We next explore the current understanding of the inductive mechanism of germ-cell determination in mice, and evaluate the hypotheses for selective pressures on these contrasting mechanisms. We then discuss the hypothesis that the transition between these determination mechanisms, which has happened many times in phylogeny, is more of a continuum than a binary change. Finally, we propose an analogy between germline determination and sex determination in vertebrates—two of the milestones of reproduction and development—in which animals use contrasting strategies to activate similar pathways. PMID:23450642

  16. Planimetric determination of lung volume

    International Nuclear Information System (INIS)

    Bieber, M.; Maurer, H.J.

    1984-01-01

    The total volume of the lungs was determined by digital planimetry in 102 patients with emphysema and 33 normal controls aged between 30 and 79 years. The results were compared with the findings obtained from spirometric measurements. Mean values showed a significant relationship to age, body size and body surface. Planimetrically determined lung volume did not show a linear relationship with age, but increased after 60 years. Beyong 60 years, spirometric findings were lower because of an increase in the number of patients with emphysema. The results have shown that digital planimetry is a useful addition to spirometry. (orig.) [de

  17. Uranium determination in dental ceramics

    International Nuclear Information System (INIS)

    Jacobson, I.; Gamboa, I.; Espinosa, G.; Moreno, A.

    1984-01-01

    There are many reports of high uranium concentration in dental ceramics, so they require to be controlled. The SSNTD is an optional method to determine the uranium concentration. In this work the analysis of several commercial dental ceramics used regularly in Mexico by dentists is presented. The chemical and electrochemical processes are used and the optimal conditions for high sensitivity are determined. CR-39 (allyl diglycol polycarbonate) was used as detector. The preliminary results show some materials with high uranium concentrations. Next step will be the analysis of equivalent dose and the effects in the public health. (author)

  18. Decoherence, determinism and chaos revisited

    Energy Technology Data Exchange (ETDEWEB)

    Noyes, H.P.

    1994-11-15

    We suggest that the derivation of the free space Maxwell Equations for classical electromagnetism, using a discrete ordered calculus developed by L.H. Kauffman and T. Etter, necessarily pushes the discussion of determinism in natural science down to the level of relativistic quantum mechanics and hence renders the mathematical phenomena studied in deterministic chaos research irrelevant to the question of whether the world investigated by physics is deterministic. We believe that this argument reinforces Suppes` contention that the issue of determinism versus indeterminism should be viewed as a Kantian antinomy incapable of investigation using currently available scientific tools.

  19. Decoherence, determinism and chaos revisited

    International Nuclear Information System (INIS)

    Noyes, H.P.

    1994-01-01

    We suggest that the derivation of the free space Maxwell Equations for classical electromagnetism, using a discrete ordered calculus developed by L.H. Kauffman and T. Etter, necessarily pushes the discussion of determinism in natural science down to the level of relativistic quantum mechanics and hence renders the mathematical phenomena studied in deterministic chaos research irrelevant to the question of whether the world investigated by physics is deterministic. We believe that this argument reinforces Suppes' contention that the issue of determinism versus indeterminism should be viewed as a Kantian antinomy incapable of investigation using currently available scientific tools

  20. AGROCLIMATIC DETERMINANTS OF IRRIGATION NEEDS

    Directory of Open Access Journals (Sweden)

    Leszek Łabędzki

    2016-05-01

    Full Text Available The paper is a review of the so far used in Poland methods and criteria for assessing the needs of irrigation for planning purposes, the assessment because of the agroclimatic conditions and taking into account the soil water retention. Irrigation needs of the most are determined taking into account crop water deficits. This is the factor that is characterized by a shortage of precipitation in relation to the water requirements of crops. Some methods use only the meteorological parameters that determine the state of the atmosphere-soil-plant system, and some also take into account soil water retention and its availability for plants.

  1. MEANS FOR DETERMINING CENTRIFUGE ALIGNMENT

    Science.gov (United States)

    Smith, W.Q.

    1958-08-26

    An apparatus is presented for remotely determining the alignment of a centrifuge. The centrifage shaft is provided with a shoulder, upon which two followers ride, one for detecting radial movements, and one upon the shoulder face for determining the axial motion. The followers are attached to separate liquid filled bellows, and a tube connects each bellows to its respective indicating gage at a remote location. Vibrations produced by misalignment of the centrifuge shaft are transmitted to the bellows, and tbence through the tubing to the indicator gage. This apparatus is particularly useful for operation in a hot cell where the materials handled are dangerous to the operating personnel.

  2. What Determines Joint Venture Termination?

    DEFF Research Database (Denmark)

    Nielsen, Bo Bernhard

    2012-01-01

    Joint venture (JV) research continues to flourish as researchers seek to advance our understanding of why so many JVs fail. Cui and Kumar (this issue) take a contingency approach to explain how and why business relatedness may provide new insights as to what determines JV termination. This commen......Joint venture (JV) research continues to flourish as researchers seek to advance our understanding of why so many JVs fail. Cui and Kumar (this issue) take a contingency approach to explain how and why business relatedness may provide new insights as to what determines JV termination...

  3. The effect of recovery from potentially lethal damage on the determination of repair and repopulation in a murine tumour

    International Nuclear Information System (INIS)

    Sheldon, P.W.; Fowler, J.F.

    1985-01-01

    Repair and repopulation following X irradiation of clamped-off murine anaplastic MT tumours was investigated using the established method of (Dsub(n)-D 1 )/(n-1). Repair was complete in 4 h, similar in extent to that reported in other tumours, and within the range of that reported for normal tissues. Subsequent repopulation commenced after 4 days and was equivalent to 1.8 Gy/day recovered dose, corresponding to a clonogenic cell number doubling time of 1.8 days. However, estimates of repair and repopulation may have been in error because the chronically hypoxic cells in this tumour alone have the ability to recover from potentially lethal damage (PLD) and so are more radioresistant than cells rendered acutely hypoxic by clamping. Because of this, even clamping off tumours at irradiation does not render all cell populations equally radioresistant, and so reoxygenation between fractions could result in an underestimate of repair and repopulation. Further, the differing sensitivity between acutely and chronically hypoxic cells renders the apparent OER a function of dose (i.e., oxygen not truly dose-modifying to chronically hypoxic cells). Consequently it is incorrect to assume a constant OER in order to compare repair in tumours irradiated under hypoxic conditions with that in normal tissues irradiated under aerobic conditions. (author)

  4. Determination experimentale des principales caracteristiques ...

    African Journals Online (AJOL)

    Through the present research work, usual scientific parameters and characteristics of Borassus palm wood from Benin, are determined. Specifically, infradensity, shrinkage coefficient and behaviour, breaking stress in the direction of the fibbers at pulling, compression and bending, are known as well as Young modulus at ...

  5. Processing Determinants of Reading Speed.

    Science.gov (United States)

    Jackson, Mark D.; McClelland, James L.

    1979-01-01

    Two groups of undergraduates differing in reading ability were tested on a number of reaction-time tasks designed to determine the speed of encoding visual information at several different levels, tests of sensory functions, verbal and quantitative reasoning ability, short-term auditory memory span, and ability to comprehend spoken text.…

  6. Bell's theorem and delayed determinism

    International Nuclear Information System (INIS)

    Franson, J.D.

    1985-01-01

    The most recent experiment by Aspect, Dalibard, and Roger does not appear to rule out a class of theories in which the outcome of an event is not determined until some time after its occurrence. This class of theories includes not only the quantum theory but various local, realistic theories as well

  7. Polyelectrolyte determination in drinking water

    African Journals Online (AJOL)

    try as there are no readily available methods for the determination of residual polyelectrolyte concentration. This study aims at ... quate, making the need to quantify them more critical (Fielding,. 1999). ... decisions and actions are sometimes required in the environ- ... were conducted on both distilled and real water systems.

  8. Second derivative spectrophotometric determination of ...

    African Journals Online (AJOL)

    A new, simple, rapid, wide applicable range and reliable second derivative spectrophotometric method has been developed for determination of cyclophosphamide (CP) in bulk and pharmaceutical dosage forms. Calibration graph is linear in the concentration range of 25 - 200 μg/ml of CP with 10 μg/ml of detection limit and ...

  9. Self-Determination and Choice

    Science.gov (United States)

    Wehmeyer, Michael L.; Abery, Brian H.

    2013-01-01

    Promoting self-determination and choice opportunities for people with intellectual and developmental disabilities has become best practice in the field. This article reviews the research and development activities conducted by the authors over the past several decades and provides a synthesis of the knowledge in the field pertaining to efforts to…

  10. Spectrophotometric determination of eflornithine hydrochloride ...

    African Journals Online (AJOL)

    Purpose: To develop and validate a spectrophotometric method for the quantitative determination of eflornithine hydrochloride as a pure compound and in pharmaceutical formulations. Methods: The method involved the reaction of the target compound with vanillin reagent at specific pH 5.6 to produce a green reddish color ...

  11. Hydrogen peroxide: importance and determination

    OpenAIRE

    Mattos, Ivanildo Luiz de; Shiraishi, Karina Antonelli; Braz, Alexandre Delphini; Fernandes, João Roberto

    2003-01-01

    A brief discussion about the hydrogen peroxide importance and its determination is presented. It was emphasized some consideration of the H2O2 as reagent (separated or combined), uses and methods of analysis (techniques, detection limits, linear response intervals, sensor specifications). Moreover, it was presented several applications, such as in environmental, pharmaceutical, medicine and food samples.

  12. Determinants of wheat noodle color

    Science.gov (United States)

    Noodles are a leading food in the world, and color is a key determinant of consumer acceptance. In this review the two prominent forms of wheat noodles are considered, white salted and alkaline. Many of the preparation and evaluation strategies are the same for both, with prominence placed on ‘brigh...

  13. Cohesin in determining chromosome architecture

    Energy Technology Data Exchange (ETDEWEB)

    Haering, Christian H., E-mail: christian.haering@embl.de [Cell Biology and Biophysics Unit, European Molecular Biology Laboratory (EMBL), Heidelberg (Germany); Jessberger, Rolf, E-mail: rolf.jessberger@tu-dresden.de [Institute of Physiological Chemistry, Dresden University of Technology, Dresden (Germany)

    2012-07-15

    Cells use ring-like structured protein complexes for various tasks in DNA dynamics. The tripartite cohesin ring is particularly suited to determine chromosome architecture, for it is large and dynamic, may acquire different forms, and is involved in several distinct nuclear processes. This review focuses on cohesin's role in structuring chromosomes during mitotic and meiotic cell divisions and during interphase.

  14. Promoting Self-Determined Education.

    Science.gov (United States)

    Deci, Edvard L.; Ryan, Richard M.

    1994-01-01

    A theory of self-determination is presented in which concepts of intrinsic motivation and extrinsic motivation are explicated and the innate psychological needs for competence, autonomy, and relatedness are discussed. A review of laboratory and field studies indicates the importance of social contexts that facilitate satisfaction of these basic…

  15. Efficient GPS Position Determination Algorithms

    National Research Council Canada - National Science Library

    Nguyen, Thao Q

    2007-01-01

    ... differential GPS algorithm for a network of users. The stand-alone user GPS algorithm is a direct, closed-form, and efficient new position determination algorithm that exploits the closed-form solution of the GPS trilateration equations and works...

  16. Self-determination after Kosovo

    DEFF Research Database (Denmark)

    . As such, the case of Kosovo has sharpened the focus and intensified the debate on the issue of self-determination conflicts and how they are managed by the international community. This volume contributes to this debate by examining Kosovo in historical and contemporary comparative perspective...... and by reflecting on the legal, ethical and political implications of its successful declaration of independence....

  17. Bell numbers, determinants and series

    Indian Academy of Sciences (India)

    In this article, we study Bell numbers and Uppuluri Carpenter numbers. We obtain various expressions and relations between them. These include polynomial recurrences and expressions as determinants of certain matrices of binomial coefficients. Keywords. p-adic series; Bell numbers. 1. Introduction. Bell numbers, Bn [2] ...

  18. Determination of nominal accelerating potential

    International Nuclear Information System (INIS)

    Nizin, P.; Kase, K.

    1986-01-01

    We present a simple linear relationship between the nominal accelerating potential (NAP) and the ratios of ionization measurements made with constant source--detector distance and at two different phantom thicknesses. This relationship can be used as a standard, unambiguous method for determining NAP for use in dosimetry and quality control

  19. Sex determination in the Hymenoptera

    NARCIS (Netherlands)

    Heimpel, George E.; de Boer, Jetske G.

    2008-01-01

    The dominant and ancestral mode of sex determination in the Hymenoptera is arrhenotokous parthenogenesis, in which diploid females develop from fertilized eggs and haploid males develop from unfertilized eggs. We discuss recent progress in the understanding of the genetic and cytoplasmic mechanisms

  20. Concurrent determination of connected components

    NARCIS (Netherlands)

    Hesselink, Wim H.; Meijster, Arnold; Bron, Coenraad

    2001-01-01

    The design is described of a parallel version of Tarjan's algorithm for the determination of equivalence classes in graphs that represent images. Distribution of the vertices of the graph over a number of processes leads to a message passing algorithm. The algorithm is mapped to a shared-memory

  1. Socioeconomic determinants of first names

    NARCIS (Netherlands)

    Bloothooft, G.; Onland, D.

    2011-01-01

    Modern naming practices in the Netherlands between 1982 and 2005 were studied on the basis of 1409 popular first names, divided into fourteen name groups determined by the common preferences of parents for the names involved. Socioeconomic variables such as family income, parents' level of

  2. Determination of osmium in molybdenites

    International Nuclear Information System (INIS)

    Schelhorn, H.; Geisler, M.

    1981-01-01

    Os has been determined in molybdenites by neutron activation analysis, measuring the 129.4 keV peak of the 191 Os spectrum after radiochemical separation. Os is removed directly as OsO 4 by distillation from the melt of an oxidizing acid or feebly basic fusion mixture

  3. Spectrophotometric Determination of Eflornithine Hydrochloride ...

    African Journals Online (AJOL)

    Purpose: To develop and validate a spectrophotometric method for the quantitative determination of eflornithine hydrochloride as a pure compound and in pharmaceutical formulations. Methods: The method involved the reaction of the target compound with vanillin reagent at specific pH. 5.6 to produce a green reddish color ...

  4. Determination of clothing microclimate volume

    NARCIS (Netherlands)

    Daanen, Hein; Hatcher, Kent; Havenith, George

    2005-01-01

    The average air layer thickness between human skin and clothing is an important factor in heat transfer. The trapped volume between skin and clothing is an estimator for everage air layer thickness. Several techniques are available to determine trapped volume. This study investigates the reliability

  5. Second derivative spectrophotometric determination of ...

    African Journals Online (AJOL)

    Hemn

    2013-11-13

    Nov 13, 2013 ... olanzapine in pharmaceutical formulation.Int.J.ChemTech. Res.2(1):756-761. Stanisz B, Paszun S, Lesniak M (2009). Validation of UV derivative spectrophotometric method for determination of benazepril hydrochloride in tablets and evaluation of its stability.ActaPoloniaePharmaceutica-Drug Research.

  6. Equipment for lustrous carbon determination

    Directory of Open Access Journals (Sweden)

    A. Witowski

    2008-07-01

    Full Text Available In this paper methods of determination of total pyrolytic carbon and its fraction: lustrous and amorphous carbon was shown. They are used in foundry industry as carbonaceous materials, i.e. in coal dust replacements and moulding sands. The principle of model analyser working, which uses NDIR module detection, and example results of such analysis were also presented.

  7. Determining Inorganic and Organic Carbon.

    Science.gov (United States)

    Koistinen, Jaana; Sjöblom, Mervi; Spilling, Kristian

    2017-11-21

    Carbon is the element which makes up the major fraction of lipids and carbohydrates, which could be used for making biofuel. It is therefore important to provide enough carbon and also follow the flow into particulate organic carbon and potential loss to dissolved organic forms of carbon. Here we present methods for determining dissolved inorganic carbon, dissolved organic carbon, and particulate organic carbon.

  8. Fermion determinants in lattice QCD

    International Nuclear Information System (INIS)

    Johnson, Christopher Andrew

    2001-01-01

    The main topic of this thesis concerns efficient algorithms for the calculation of determinants of the kind of matrix typically encountered in lattice QCD. In particular an efficient method for calculating the fermion determinant is described. Such a calculation is useful to illustrate the effects of light dynamical (virtual) quarks. The methods employed in this thesis are stochastic methods, based on the Lanczos algorithm, which is used for the solution of large, sparse matrix problems via a partial tridiagonalisation of the matrix. Here an implementation is explored which requires less exhaustive treatment of the matrix than previous Lanczos methods. This technique exploits the analogy between the Lanczos tridiagonalisation algorithm and Gaussian quadrature in order to calculate the fermion determinant. A technique for determining a number of the eigenvalues of the matrix is also presented. A demonstration is then given of how one can improve upon this estimate considerably using variance reduction techniques, reducing the variance by a factor of order 100 with a further, equal amount of work. The variance reduction method is a two-stage process, involving a Chebyshev approximation to the quantity in question and then the subtraction of traceless operators. The method is applied to the fermion determinant for non-perturbatively improved Wilson fermions on a 16 3 x 32 lattice. It is also applicable to a wider class of matrix operators. Finally we discuss how dynamical quark effects may be simulated in a Monte Carlo process with an effective partitioning of low and high eigenmodes. This may be done via selective updating of a trial configuration which highlights the physically relevant effects of light quark modes. (author)

  9. Determination of radium in water

    Energy Technology Data Exchange (ETDEWEB)

    Hohorst, F.A.; Huntley, M.W.; Hartenstein, S.D.

    1995-10-01

    These detailed work instructions (DWIs) are tailored for the analysis of radium-226 and radium-228 in drinking water supplies from ground water and surface water sources and composites derived from them. The instructions have been adapted from several sources, including a draft EPA method. One objective was to minimize the generation of mixed wastes. Quantitative determinations of actinium-228 are made at 911 keV. The minimum detection level (MDL) for the gamma spectrometric measurements at this energy vary with matrix, volume, geometry, detector, background, and counting statistics. The range of MDL`s for current detectors is 0.07 to 0.5 Bq/sample. Quantitative determinations of radium-226 are made by counting the high energy alpha particles which radium-226 progeny emit using liquid scintillation counting (LSC). The minimum detectable activity (MDA) is 3.8 E-3 Bq/sample. The maximum concentration which may be counted on available instruments without dilution is about 2 E + 5 Bq/sample. Typically, this determination of radium in a 2 L sample has a yield of 80%. If radium-228 is determined using a 16 h count after 50 h grow-in, the typical MDL is 1 E-9 to 8 E-9 {mu}Ci/mL (1 to 8 pCi/L). If radium-226 is determined using a 2.5 h count after 150 h grow-in, the typical MDA is about 1 E-10 {mu}Ci/mL (0. 1 pCi/L).

  10. Determination of radium in water

    International Nuclear Information System (INIS)

    Hohorst, F.A.; Huntley, M.W.; Hartenstein, S.D.

    1995-10-01

    These detailed work instructions (DWIs) are tailored for the analysis of radium-226 and radium-228 in drinking water supplies from ground water and surface water sources and composites derived from them. The instructions have been adapted from several sources, including a draft EPA method. One objective was to minimize the generation of mixed wastes. Quantitative determinations of actinium-228 are made at 911 keV. The minimum detection level (MDL) for the gamma spectrometric measurements at this energy vary with matrix, volume, geometry, detector, background, and counting statistics. The range of MDL's for current detectors is 0.07 to 0.5 Bq/sample. Quantitative determinations of radium-226 are made by counting the high energy alpha particles which radium-226 progeny emit using liquid scintillation counting (LSC). The minimum detectable activity (MDA) is 3.8 E-3 Bq/sample. The maximum concentration which may be counted on available instruments without dilution is about 2 E + 5 Bq/sample. Typically, this determination of radium in a 2 L sample has a yield of 80%. If radium-228 is determined using a 16 h count after 50 h grow-in, the typical MDL is 1 E-9 to 8 E-9 μCi/mL (1 to 8 pCi/L). If radium-226 is determined using a 2.5 h count after 150 h grow-in, the typical MDA is about 1 E-10 μCi/mL (0. 1 pCi/L)

  11. Determining Factors of Subsidiary Development

    DEFF Research Database (Denmark)

    Pedersen, Torben

    (the depth of activities) and level of integration in the internal MNC-network. Birkinshaw and Hood (1998a) have in their seminal paper proposed a model where subsidiary development is determined by three factors: Headquarter assignment, dynamism of local business environment and subsidiary initiatives......Subsidiary development is a multi-dimensional construct that cannot be captured just by looking at subsidiary roles, activities, etc. Three distinct dimensions of subsidiary development are identified and these are: scope of subsidiary (the breadth of activities), level of subsidiary competence....... This paper is the first to conduct a statistical test of this model on a large-sample data set including data of more than 2.100 subsidiaries located in seven different countries in Europe. The effect of the three determining factors on subsidiary development is tested simultaneously in a LISREL model....

  12. Dose determination in computed tomography

    International Nuclear Information System (INIS)

    Descamps, C.; Garrigo, E.; Venencia, D.; Gonzalez, M.; Germanier, A.

    2011-10-01

    In the last years the methodologies to determine the dose in computed tomography have been revised. In this work was realized a dosimetric study about the exploration protocols used for simulation of radiotherapy treatments. The methodology described in the Report No. 111 of the American Association of Medical Physiques on a computed tomograph of two cuts was applied. A cylindrical phantom of water was used with dimensions: 30 cm of diameter and 50 cm of longitude that simulates the absorption and dispersion conditions of a mature body of size average. The doses were determined with ionization chamber and thermoluminescent dosimetry. The results indicate that the dose information that provides the tomograph underestimates the dose between 32 and 35%.

  13. Cell Elasticity Determines Macrophage Function

    Science.gov (United States)

    Patel, Naimish R.; Bole, Medhavi; Chen, Cheng; Hardin, Charles C.; Kho, Alvin T.; Mih, Justin; Deng, Linhong; Butler, James; Tschumperlin, Daniel; Fredberg, Jeffrey J.; Krishnan, Ramaswamy; Koziel, Henry

    2012-01-01

    Macrophages serve to maintain organ homeostasis in response to challenges from injury, inflammation, malignancy, particulate exposure, or infection. Until now, receptor ligation has been understood as being the central mechanism that regulates macrophage function. Using macrophages of different origins and species, we report that macrophage elasticity is a major determinant of innate macrophage function. Macrophage elasticity is modulated not only by classical biologic activators such as LPS and IFN-γ, but to an equal extent by substrate rigidity and substrate stretch. Macrophage elasticity is dependent upon actin polymerization and small rhoGTPase activation, but functional effects of elasticity are not predicted by examination of gene expression profiles alone. Taken together, these data demonstrate an unanticipated role for cell elasticity as a common pathway by which mechanical and biologic factors determine macrophage function. PMID:23028423

  14. Cell elasticity determines macrophage function.

    Directory of Open Access Journals (Sweden)

    Naimish R Patel

    Full Text Available Macrophages serve to maintain organ homeostasis in response to challenges from injury, inflammation, malignancy, particulate exposure, or infection. Until now, receptor ligation has been understood as being the central mechanism that regulates macrophage function. Using macrophages of different origins and species, we report that macrophage elasticity is a major determinant of innate macrophage function. Macrophage elasticity is modulated not only by classical biologic activators such as LPS and IFN-γ, but to an equal extent by substrate rigidity and substrate stretch. Macrophage elasticity is dependent upon actin polymerization and small rhoGTPase activation, but functional effects of elasticity are not predicted by examination of gene expression profiles alone. Taken together, these data demonstrate an unanticipated role for cell elasticity as a common pathway by which mechanical and biologic factors determine macrophage function.

  15. System for determining aerodynamic imbalance

    Science.gov (United States)

    Churchill, Gary B. (Inventor); Cheung, Benny K. (Inventor)

    1994-01-01

    A system is provided for determining tracking error in a propeller or rotor driven aircraft by determining differences in the aerodynamic loading on the propeller or rotor blades of the aircraft. The system includes a microphone disposed relative to the blades during the rotation thereof so as to receive separate pressure pulses produced by each of the blades during the passage thereof by the microphone. A low pass filter filters the output signal produced by the microphone, the low pass filter having an upper cut-off frequency set below the frequency at which the blades pass by the microphone. A sensor produces an output signal after each complete revolution of the blades, and a recording display device displays the outputs of the low pass filter and sensor so as to enable evaluation of the relative magnitudes of the pressure pulses produced by passage of the blades by the microphone during each complete revolution of the blades.

  16. Multilevel Determinants of Childhood Obesity

    OpenAIRE

    Chang, Yen-Jung

    2012-01-01

    The prevalence of obesity among US children and adolescents has rapidly increased in the past several decades, and the epidemic of childhood obesity is currently a serious public health concern in the United States. This dissertation consists of three studies examining individual- and neighborhood-level determinants of childhood obesity. The study area was Los Angeles County in California. Our first study examined the effects of maternal employment, individual socioeconomic status (SES), and ...

  17. Firm Decisions: Determinants of Investments

    OpenAIRE

    Ionescu Alexandra

    2011-01-01

    The investment decision is part of a companies’ investment strategy. Defined as a logical set of technical and economic information, the investment strategy determines the main objectives of the firm regarding its investments, based on studies, analysis and simulations. It also establishes the actions to be undertaken in order to achieve the objectives, methods of achieving them, sources of funding and resource allocation methods. Still, all these are influenced by several factors. The invest...

  18. Determinants of flexible work arrangements

    OpenAIRE

    Sarbu, Miruna

    2014-01-01

    Flexible work arrangements such as allowing employees to work at home are used in firms, especially since information and communication technologies have become so widespread. Using individual-level data from 10,884 German employees, this paper analyses the determinants of working at home as a form of flexible work arrangements. The analysis is based on descriptive analyses and a discrete choice model using a probit estimation approach. The results reveal that men have a higher...

  19. Determining FDI Flows into Scandinavia

    DEFF Research Database (Denmark)

    Kottaridi, Constantina; Bernhard Nielsen, Bo

    2003-01-01

    AbstractIn a recent global competitiveness report by the IMF, the four Nordic countries all ranked in top ten, attesting to the region?s growing attractiveness as a host location for MNCs. This paper investigates the driving forces determining foreign direct investment flows into Scandinavia. We...... for the changing pattern of international production indicating strategic needs for MNCs to acquire assets and technology that are specific to particular locations....

  20. Factors determining UK album success

    OpenAIRE

    Elliott, Caroline; Simmons, Robert

    2011-01-01

    This article uses a recently compiled dataset on the UK album sales to determine which factors contribute to best-selling album sales success. We control for factors including length of time since release, nationality of artist, artist type and album type, testing the increasing returns to information hypothesis. Information on general public online review scores for the albums in the dataset allows for a strong test of the accuracy of online reviews in predicting music sales, as online revie...

  1. Determination of americium in urine

    International Nuclear Information System (INIS)

    Shvydko, N.S.; Mikhajlova, O.A.; Popov, D.K.

    1988-01-01

    A technique has been developed for the determination of americium 241 in urine by a raiochemical purification of the nuclide from uranium (upon co-precipitation of americium 241 with calcium and lanthanum), plutonium, thorum, and polonium 210 (upon co-precipitation of these radionuclides with zirconium iodate). α-Radioactivity was measured either in a thick layer of the americium 241 precipitate with a nonisotope carrier or in thin-layer preparations after electrolytic precipitation of americium 241 on a cathode

  2. Determining seed moisture in Quercus

    Science.gov (United States)

    F. T. Bonner

    1974-01-01

    The air-oven method with drying times 7 to 8 hours shorter than those now prescribed in the ISTA rules proved adequate for determining moisture contents in acorns of several North American oaks. Schedules of 8 hours at 105°C for Quercus muehlenbergii and 9 hours at 105°C for Q.shumardii and Q.nigra gave moisture contents within three percentage points of those obtained...

  3. International Development Aid Allocation Determinants

    OpenAIRE

    Tapas Mishra; Bazoumana Ouattara; Mamata Parhi

    2012-01-01

    This paper investigates the factors explaining aid allocation by bilateral and multilateral donors. We use data for 146 aid recipient countries over the period 1990-2007 and employ Bayesian Averaging of Classical Estimates Approach (BACE) approach and find that both the recipient need and donor interest motives are `significant' determinants of bilateral and multilateral aid allocation process. Our results also indicate that the measures for recipient need and donor interests vary from bilate...

  4. Determining Σ-Λ mixing

    Energy Technology Data Exchange (ETDEWEB)

    Horsley, R. [Edinburgh Univ. (United Kingdom). School of Physics and Astronomy; Najjar, J. [Regensburg Univ. (Germany). Inst. fuer Theoretische Physik; Nakamura, Y. [RIKEN Advanced Institute for Computational Science, Kobe (Japan); Perlt, H.; Schiller, A. [Leipzig Univ. (Germany). Inst. fuer Theoretische Physik; Pleiter, D. [Forschungszentrum Juelich GmbH (Germany). Juelich Supercomputing Centre (JSC); Regensburg Univ. (Germany). Inst. fuer Theoretische Physik; Rakow, P.E.L. [Liverpool Univ. (United Kingdom). Theoretical Physics Div.; Schierholz, G. [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Stueben, H. [Hamburg Univ. (Germany). Regionales Rechenzentrum; Zanotti, J.M. [Adelaide Univ. (Australia). CSSM, School of Chemistry and Physics

    2014-12-15

    SU2 isospin breaking effects in baryon octet (and decuplet) masses are due to a combination of up and down quark mass differences and electromagnetic effects. These mass differences are small. Between the Sigma and Lambda the mass splitting is much larger, but this is mostly due to their different wavefunctions. However there is now also mixing between these states. We determine the QCD mixing matrix and hence find the mixing angle and mass splitting.

  5. Controversies in urinary iodine determinations

    OpenAIRE

    Soldin, Offie Porat

    2002-01-01

    Iodine deficiency (ID) is associated with increased prevalence of goiter, increased risk for neurodevelopmental disorders, and is the world’s leading cause of intellectual deficits. Iodine nutritional status of a population is assessed by measurements of urinary iodine concentrations which are also used to define, indicate, survey and monitor iodine deficiency and consequently its treatment. Several methods are available for urinary iodine determination. Discussed here are some of the limitat...

  6. DETERMINANTS OF FAST FOOD CONSUMPTION

    OpenAIRE

    Fanning, Jasper; Marsh, Thomas L.; Stiegert, Kyle W.

    2002-01-01

    Socioeconomic determinants are investigated for both the likelihood of consuming fastfood and household expenditure on fastfood using the 1994-98 USDA Continuing Survey of Food Intakes by Individuals. The logit model is used to estimate an empirical relationship between probability an individual will consume fastfood and socioeconomic variables. The Tobit model is used to estimate an empirical relationship between expenditure on fastfood and socioeconomic variables. Significant socioeconomic ...

  7. Ultramicromethod of immunreactive insulin determination

    International Nuclear Information System (INIS)

    Tyrkolev, N.

    1979-01-01

    A radioimmunologic method of immunoreactive insulin (IRI) determination, requiring 0,02 ml biologic fluid for a single determination, is described. The basic method used in this study, is the thoroughly investigated and for many years applied by the author coal dextran method of IRI determination. The reagents, the scheme of practical performance of the test and calculation of the results are described, and an exemplary standard curve presented. A trial of the method was attempted by comparing the results by the standard and the ultramicromethod. The differences were statistically insignificant. The data of the standard curves of these experiments were also statistically processed. Fifty two sera with different insulin levels (9-275μU/ml) were subjected to comparative IRI assay by either method. They were spanned according to their IRI content, with calculations of the differences between the two methods in the different age groups. A diagram of a single glucose leading (n equals 4) by the two methods is presented. The practical identity of the results obtained by the two methods and the advantages of the ultramicromethod are emphasized. (author)

  8. Determination of environmental radioactivity, 8

    International Nuclear Information System (INIS)

    Takagi, Shinji; Nakaoka, Akira; Fukushima, Masanori; Tsukamoto, Masaki

    1984-01-01

    According to the fundamental design proposed for the purpose of dose assessment of the general public around a nuclear facility corresponding to the guideline issued by the Atomic Energy Commission of Japan, 5 mrem/yr, the authors developed a rapid and simple determination method of radioactivity in food and related environmental samples by pretreating with a modified microwave dehydration apparatus followed by radiation counting. Equation to estimate heating condition by the apparatus was derived, and estimation by the equation was in good agreement with experimental data. It took less than 4.5 hours to dehydrate by the proposed method. This value was much smaller in comparison with the value of more than 10 hours by a conventional hot-air drying method, and radiation counting was able to be started in the same day of sampling and dehydration procedure. It was cralified that lower limits of detection for each radionuclide by the proposed method by using a Ge(Li) detector of 20 % relative efficiency was lower than half level of needed detection limits to determine and evaluate the 5 mrem/yr level. Radionuclide levels in food samples such as vegetables and crustaceans was determined by the proposed method and it was found that they were below the lower detection limit of the method except natural radionuclide 40 K and fallout originated 137 Cs. (author)

  9. Mathematical determination of image quality

    Energy Technology Data Exchange (ETDEWEB)

    Barrett, H H

    1982-01-01

    The subjective term ''image quality'' is generally not easy to define and to measure. If, however, we limit ourselves, to determine certain anomalies in blurred images, then the task can be done more easily. The efficiency can in fact be measured and the results can be presented as ROC-characteristics (receiver operating characteristics). One can determine a relation between the characteristic and the noise distance of the imaging system, and this way the efficiency of an hypothetical ideal observer can be predicted. Furthermore one can compute noise distance and other statistical parameters of X-ray images distorted by quantum interference by special techniques that are founded on the so-called ''blur core''. The technique proved to be very successful in nuclear medicine, but is also valid in computerized tomography and X-ray diagnostics. The technique is explained without mathematical details. The question will be answered concerning the role mathematical analysis will play in the determination and optimization of the quality of diagnostic exposures.

  10. [Monitoring social determinants of health].

    Science.gov (United States)

    Espelt, Albert; Continente, Xavier; Domingo-Salvany, Antonia; Domínguez-Berjón, M Felicitas; Fernández-Villa, Tania; Monge, Susana; Ruiz-Cantero, M Teresa; Perez, Glòria; Borrell, Carme

    2016-11-01

    Public health surveillance is the systematic and continuous collection, analysis, dissemination and interpretation of health-related data for planning, implementation and evaluation of public health initiatives. Apart from the health system, social determinants of health include the circumstances in which people are born, grow up, live, work and age, and they go a long way to explaining health inequalities. A surveillance system of the social determinants of health requires a comprehensive and social overview of health. This paper analyses the importance of monitoring social determinants of health and health inequalities, and describes some relevant aspects concerning the implementation of surveillance during the data collection, compilation and analysis phases, as well as dissemination of information and evaluation of the surveillance system. It is important to have indicators from sources designed for this purpose, such as continuous records or periodic surveys, explicitly describing its limitations and strengths. The results should be published periodically in a communicative format that both enhances the public's ability to understand the problems that affect them, whilst at the same time empowering the population, with the ultimate goal of guiding health-related initiatives at different levels of intervention. Copyright © 2016 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

  11. Polycyclic hydrocarbons - occurrence and determination

    International Nuclear Information System (INIS)

    Drzewicz, P.

    2007-01-01

    Polycyclic aromatic hydrocarbons (PAHs) are a special group of atmospheric contaminants included in the persistent toxic substances (PTS) and also in the volatile organic compounds (VOC) groups. PAHs are present in the atmosphere and their origin can be due to anthropogenic activities. The main source of emission of PAH is the combustion of fossil fuels. Their specific characteristics, high volatility, mutagenic and carcinogenic power, easily transportable for long distances with the wind, make them important contaminants despite of the fact that they are present at very low concentrations. The report provides a review of main analytical methods applied in the determination of PAH in air. Special attention was devoted to heterocyclic PAH which contain one or more heteroatom (sulphur, oxygen, nitrogen) in the multiple-fused ring. The presence of heterocyclic PAH requires very complex, laborious and long lasting sample separation methods before analysis. In some cases, application of different temperature programs in gas chromatography allows to determine PAH and heterocyclic PAH in gaseous samples without sample pretreatment. Gas chromatography methods for the determination of PAH and heterocyclic PAH in the gas from combustion of light heating oil has been optimized. (author) [pl

  12. Plutonium determination by isotope dilution

    International Nuclear Information System (INIS)

    Lucas, M.

    1980-01-01

    The principle is to add to a known amount of the analysed solution a known amount of a spike solution consisting of plutonium 242. The isotopic composition of the resulting mixture is then determined by surface ionization mass spectrometry, and the plutonium concentration in the solution is deduced, from this measurement. For irradiated fuels neutronic studies or for fissile materials balance measurements, requiring the knowledge of the ratio U/Pu or of concentration both uranium and plutonium, it is better to use the double spike isotope dilution method, with a spike solution of known 233 U- 242 Pu ratio. Using this method, the ratio of uranium to plutonium concentration in the irradiated fuel solution can be determined without any accurate measurement of the mixed amounts of sample and spike solutions. For fissile material balance measurements, the uranium concentration is determined by using single isotope dilution, and the plutonium concentration is deduced from the ratio Pu/U and U concentration. The main advantages of isotope dilution are its selectivity, accuracy and very high sensitivity. The recent improvements made to surface ionization mass spectrometers have considerably increased the precision of the measurements; a relative precision of about 0.2% to 0.3% is obtained currently, but it could be reduced to 0.1%, in the future, with a careful control of the experimental procedures. The detection limite is around 0.1 ppb [fr

  13. [Mental Health: Concepts, Measures, Determinants].

    Science.gov (United States)

    Doré, Isabelle; Caron, Jean

    Objectives This article aims to situate the concept of mental health in a historical perspective. This article presents the most commonly used measurement tools in Canada and elsewhere in the world to assess specific and multiple dimensions of mental health; when available, psychometric properties are discussed. Finally, research findings on quality of life and mental health determinants are presented.Methods A literature review of concepts, measurement and determinants of mental health is presented in this paper. The selection of measurement scales presented is based on the findings of the research reports conducted by the second author, an expert on mental health measures, for Health Canada and Statistics Canada.Results Mental health is more than the absence of mental illness; rather it is a state of complete well-being, which refers to our ability to enjoy life and deal with the challenges we face. Accordingly, mental health and mental illness are not extremes of the same continuum, but distinct yet correlated concepts. The traditional conceptualization suggesting that mental health represents simply the absence of mental illness has been replaced, in the last few decades, by a more holistic characterization, which directly concerns public health. The components of mental health include emotional well-being/quality of life (QOL) and psychological and social well-being. Mental health influences the personal and social functioning of individuals, justifying the importance of intervening upstream to promote mental health. Specific scales are relevant for obtaining a detailed measure of one aspect of well-being in particular (emotional/quality of life, psychological or social well-being); however, to account for the global mental health status, measurement tools that integrate all three forms of well-being (emotional, psychological and social) should be privileged. A diversity of determinants at the individual, social and neighbourhood levels influence quality of

  14. The molecular basis of FHA domain:phosphopeptide binding specificity and implications for phospho-dependent signaling mechanisms.

    Science.gov (United States)

    Durocher, D; Taylor, I A; Sarbassova, D; Haire, L F; Westcott, S L; Jackson, S P; Smerdon, S J; Yaffe, M B

    2000-11-01

    Forkhead-associated (FHA) domains are a class of ubiquitous signaling modules that appear to function through interactions with phosphorylated target molecules. We have used oriented peptide library screening to determine the optimal phosphopeptide binding motifs recognized by several FHA domains, including those within a number of DNA damage checkpoint kinases, and determined the X-ray structure of Rad53p-FHA1, in complex with a phospho-threonine peptide, at 1.6 A resolution. The structure reveals a striking similarity to the MH2 domains of Smad tumor suppressor proteins and reveals a mode of peptide binding that differs from SH2, 14-3-3, or PTB domain complexes. These results have important implications for DNA damage signaling and CHK2-dependent tumor suppression, and they indicate that FHA domains play important and unsuspected roles in S/T kinase signaling mechanisms in prokaryotes and eukaryotes.

  15. Topographic Effects in Geoid Determinations

    Directory of Open Access Journals (Sweden)

    Lars E. Sjöberg

    2018-04-01

    Full Text Available Traditionally, geoid determination is applied by Stokes’ formula with gravity anomalies after removal of the attraction of the topography by a simple or refined Bouguer correction, and restoration of topography by the primary indirect topographic effect (PITE after integration. This technique leads to an error of the order of the quasigeoid-to-geoid separation, which is mainly due to an incomplete downward continuation of gravity from the surface to the geoid. Alternatively, one may start from the modern surface gravity anomaly and apply the direct topographic effect on the anomaly, yielding the no-topography gravity anomaly. After downward continuation of this anomaly to sea-level and Stokes integration, a theoretically correct geoid height is obtained after the restoration of the topography by the PITE. The difference between the Bouguer and no-topography gravity anomalies (on the geoid or in space is the “secondary indirect topographic effect”, which is a necessary correction in removing all topographic signals. In modern applications of an Earth gravitational model (EGM in geoid determination a topographic correction is also needed in continental regions. Without the correction the error can range to a few metres in the highest mountains. The remove-compute-restore and Royal Institute of Technology (KTH techniques for geoid determinations usually employ a combination of Stokes’ formula and an EGM. Both techniques require direct and indirect topographic corrections, but in the latter method these corrections are merged as a combined topographic effect on the geoid height. Finally, we consider that any uncertainty in the topographic density distribution leads to the same error in gravimetric and geometric geoid estimates, deteriorating GNSS-levelling as a tool for validating the topographic mass distribution correction in a gravimetric geoid model.

  16. SPIRITUAL DETERMINANTS OF SUSTAINABLE DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    M. I. Bilalov

    2016-01-01

    Full Text Available Aim. The aim of the research is to study the specific determinants, motivational factors, tools and approaches that make up the mechanism for the implementation of sustainable development (the region of Southern Russia.Material and methods. As the main methodological approach, the author used the civilizational method including philosophy and political science which effectively evaluate and analyze a concrete historical stage of development of a society, a short period of its history. At the same time, as a particularly important factor and determinant of social development, we put culture, mental and religious terms of spiritual life of the peoples of the South of Russia into to the forefront, which is seen as a local independent civilization. We see the methodological innovation in the understanding of sustainable development based on the principle of ecocentrism, the equality between generations, types and groups, with regard to the principle of universal evolutionism.Results. It is assumed that civilizations develop independently and realize its cultural potential in various areas, while ethnic groups, nations and peoples with their specific culture must respect the principle of equal moral functioning. The threat of a global catastrophe and attitude for sustainable development bring spiritual values of traditional civilizations to the forefront, which are collectivism, harmony between man and nature, self-limitation, reliance on national culture and other issues that have always been fundamental to Dagestan and the North Caucasus.Conclusions. Sustainable development of the South Russian regions, including Dagestan, is possible only on the basis of the given spiritual determinants in the direction of a global civil society.

  17. Liquid chromatographic determination of water

    Science.gov (United States)

    Fortier, N.E.; Fritz, J.S.

    1990-11-13

    A sensitive method for the determination of water in the presence of common interferences is presented. The detection system is based on the effect of water on the equilibrium which results from the reaction aryl aldehydes, such as cinnamaldehyde and methanol in the eluent to form cinnamaldehyde dimethylacetal, plus water. This equilibrium is shifted in a catalytic atmosphere of a hydrogen ion form past column reactor. The extent of the shift and the resulting change in absorbance are proportional to the amount of water present. 1 fig.

  18. Accurate determination of antenna directivity

    DEFF Research Database (Denmark)

    Dich, Mikael

    1997-01-01

    The derivation of a formula for accurate estimation of the total radiated power from a transmitting antenna for which the radiated power density is known in a finite number of points on the far-field sphere is presented. The main application of the formula is determination of directivity from power......-pattern measurements. The derivation is based on the theory of spherical wave expansion of electromagnetic fields, which also establishes a simple criterion for the required number of samples of the power density. An array antenna consisting of Hertzian dipoles is used to test the accuracy and rate of convergence...

  19. Present art of reactivity determination

    International Nuclear Information System (INIS)

    Kaneko, Yoshihiko; Nakano, Masafumi; Matsuura, Shojiro

    1977-01-01

    Experimental techniques for reactivity determination of a reactor have been one of the long standing subjects in reactor physics. Recently, such a requirement was proposed by the reactor designers and operators that the values of reactivity should be measured more accurately. This is because importance is emphasized for the role of reactivity to the performance of reactor safety, economics and operability. Motivated by the requirement, some remarkable progresses are being made for the improvement of the experimental techniques. Then, the present review summarizes the research activities on this subject, identifies several reactor physics problems to be overcome, and makes mention of the future targets. (auth.)

  20. Gender specific determinants of goitre

    International Nuclear Information System (INIS)

    Jamshid, F.; Kerstin, C.; Elena, G.; Wilhelm, O.; Karl, W.; Hwe, M.

    2004-01-01

    Despite the strong implications of differences between females and males in the risk of goitre, gender-specific issues have not been extensively addressed in investigations of goitre prevalence. The Objective of our analysis was to investigate the gender-specific determinants of goitre. Methods: A total of 853 healthy employees from 4 institutions in western part of Germany aged between 18 and 68 years were examined by ultrasound of the neck to determine the thyroid volume between April 2001 and April 2002. Information on sex, age, daily use of iodised salt, the history of goitre in the first degree relatives, type and amount of' smoking, oral contraceptives and number of pregnancies were assessed by standardised questionnaires. Gender-specific predictors of goitre prevalence were assessed by multivariate logistic regression. Results: The overall prevalence of goitre among study subjects was (204/853) 23.9%. Goitre was present in 80 out of 370 females (21.6%) vs. 124/483 (25.7%) in males.In general smoking (<0.0001), increasing age (p<0.0001) and lack of daily intake of iodised salt (p=0.004) associated with goitre prevalence, but not sex (0.4) and family history of goitre (p=0.2). In 370 females, parity (p=0.004) and lack of daily intake of iodised salt (p=0.01) were the major determinants for goitre, whereas, age (p=0.2), oral contraceptives (p=0.8), family history of goitre (p=0.3), and smoking (p=0.1) did not affect the goitre prevalence. In 483 males, smoking (p<0.0001) and age (p<0.001) affected the goitre prevalence, but not family history of goitre (p=0.4) and the iodine status failed just to reach the significant level (p=0.08) in this analysis. Conclusions: Gender specific determinants of goitre are parity and iodine status in females and smoking and increasing age in males. (authors)

  1. Radiochemical method for determining treadwear

    International Nuclear Information System (INIS)

    Patel, A.C.

    1975-01-01

    A method for determining amount of treadwear of a tire is disclosed. The tire tread surface is impregnated with a radioactive material (iodine dissolved in toluene) and initial radioactivity measured at the tread surface. Subsequent measurements of radioactivity after wearing away tread indicate the amount of tread loss, when such measurements are compared with a calibration curve of radioactivity prepared for rubber of same composition and radioactive material of same concentration. Calibration curves are made by mechanically measuring loss of tread thickness of radioactive-impregnated rubber samples and measuring corresponding radioactivity remaining. (auth)

  2. Angle independent velocity spectrum determination

    DEFF Research Database (Denmark)

    2014-01-01

    An ultrasound imaging system (100) includes a transducer array (102) that emits an ultrasound beam and produces at least one transverse pulse-echo field that oscillates in a direction transverse to the emitted ultrasound beam and that receive echoes produced in response thereto and a spectral vel...... velocity estimator (110) that determines a velocity spectrum for flowing structure, which flows at an angle of 90 degrees and flows at angles less than 90 degrees with respect to the emitted ultrasound beam, based on the received echoes....

  3. Genetic sex determination and extinction.

    Science.gov (United States)

    Hedrick, Philip W; Gadau, Jürgen; Page, Robert E

    2006-02-01

    Genetic factors can affect the probability of extinction either by increasing the effect of detrimental variants or by decreasing the potential for future adaptive responses. In a recent paper, Zayed and Packer demonstrate that low variation at a specific locus, the complementary sex determination (csd) locus in Hymenoptera (ants, bees and wasps), can result in a sharply increased probability of extinction. Their findings illustrate situations in which there is a feedback process between decreased genetic variation at the csd locus owing to genetic drift and decreased population growth, resulting in an extreme type of extinction vortex for these ecologically important organisms.

  4. Ultrasonographic determination of fetal gender

    International Nuclear Information System (INIS)

    Kim, Il Young; Kim, Dae Ho; Lee, Byung Ho; Bae, Dong Han

    1985-01-01

    Sonographic determination of fetal gender was attempted prospectively in most pregnancies of more than 26 weeks. We studied 193 cases of pregnancies with ultrasound for recent 9 months from June 1984 to February 1985 at department of radiology, Soonchunhyang university, Soonchunhyang Chunan hospital, and analysed ultrasonographic finding of fetal gender. The results were as follows; 1. Overall accuracy rate for fetal gender is 90%. 2. Accuracy rate for male fetus is 97.8%. 3. Accuracy rate for female fetus is 88.2%

  5. Genetic modification and genetic determinism

    Science.gov (United States)

    Resnik, David B; Vorhaus, Daniel B

    2006-01-01

    In this article we examine four objections to the genetic modification of human beings: the freedom argument, the giftedness argument, the authenticity argument, and the uniqueness argument. We then demonstrate that each of these arguments against genetic modification assumes a strong version of genetic determinism. Since these strong deterministic assumptions are false, the arguments against genetic modification, which assume and depend upon these assumptions, are therefore unsound. Serious discussion of the morality of genetic modification, and the development of sound science policy, should be driven by arguments that address the actual consequences of genetic modification for individuals and society, not by ones propped up by false or misleading biological assumptions. PMID:16800884

  6. Fluence determination by scattering measurements

    CERN Document Server

    Albergo, S; Potenza, R; Tricomi, A; Pillon, M; Angarano, M M; Creanza, D; De Palma, M

    2000-01-01

    An alternative method to determine particle fluence is proposed, which is particularly suitable for irradiations with low-energy charged-particle beams. The fluence is obtained by measuring the elastic scattering produced by a composite thin target placed upstream of the sample. The absolute calibration is performed by comparison with the measured radioactivation of vanadium and copper samples. The composite thin target, made of aluminium, carbon and gold, allows not only the fluence to be measured, but also a continuous monitoring of the beam space distribution. Experimental results with a 27 MeV proton beam are reported and compared with Monte Carlo simulations. (7 refs).

  7. Reactor vital equipment determination techniques

    International Nuclear Information System (INIS)

    Bott, T.F.; Thomas, W.S.

    1983-01-01

    The Reactor Vital Equipment Determination Techniques program at the Los Alamos National Laboratory is discussed. The purpose of the program is to provide the Nuclear Regulatory Commission (NRC) with technical support in identifying vital areas at nuclear power plants using a fault-tree technique. A reexamination of some system modeling assumptions is being performed for the Vital Area Analysis Program. A short description of the vital area analysis and supporting research on modeling assumptions is presented. Perceptions of program modifications based on the research are outlined, and the status of high-priority research topics is discussed

  8. Determinants of internet poker adoption.

    Science.gov (United States)

    Philander, Kahlil S; Abarbanel, B Lillian

    2014-09-01

    In nearly all jurisdictions, adoption of a new form of gambling has been a controversial and contentious subject. Online gambling has been no different, though there are many aspects that affect online gambling that do not appear in the brick and mortar environment. This study seeks to identify whether demographic, economic, political, technological, and/or sociological determinants contribute to online poker gambling adoption. A theoretical discussion of these categories' importance to online poker is provided and exploratory empirical analysis is used to examine their potential validity. The analysis revealed support for all of the proposed categories of variables thought to be predictive of online gambling legality.

  9. The determinants of oil prices

    International Nuclear Information System (INIS)

    Angelier, J-P.

    1991-01-01

    In recent years, swings in oil prices have been of unprecendented severity and frequency. Three factors work together to determine the price of oil: in the short term, the balance between supply and demand; in the medium term, the structure of the oil industry; and in the long term, the marginal production cost consistent with world oil demand. An oil price forecast is presented based on these considerations, and it is predicted that in the year 2000, oil prices will not be significantly different from those of today. 28 refs

  10. Hidden Liquidity: Determinants and Impact

    OpenAIRE

    Gökhan Cebiroglu; Ulrich Horst

    2012-01-01

    We cross-sectionally analyze the presence of aggregated hidden depth and trade volume in the S&P 500 and identify its key determinants. We find that the spread is the main predictor for a stock’s hidden dimension, both in terms of traded and posted liquidity. Our findings moreover suggest that large hidden orders are associated with larger transaction costs, higher price impact and increased volatility. In particular, as large hidden orders fail to attract (latent) liquidity to the market, ...

  11. Crystal structure determination of Efavirenz

    International Nuclear Information System (INIS)

    Popeneciu, Horea; Dumitru, Ristoiu; Tripon, Carmen; Borodi, Gheorghe; Pop, Mihaela Maria

    2015-01-01

    Needle-shaped single crystals of the title compound, C 14 H 9 ClF 3 NO 2 , were obtained from a co-crystallization experiment of Efavirenz with maleic acid in a (1:1) ratio, using methanol as solvent. Crystal structure determination at room temperature revealed a significant anisotropy of the lattice expansion compared to the previously reported low-temperature structure. In both low- and room temperature structures the cyclopropylethynyl fragment in one of the asymmetric unit molecules is disordered. While at low-temperature only one C atom exhibits positional disorder, at room temperature the disorder is present for two C atoms of the cyclopropane ring

  12. DETERMINANT OF DOWNWARD AUDITOR SWITCHING

    Directory of Open Access Journals (Sweden)

    Totok Budisantoso

    2017-12-01

    Full Text Available Abstract: Determinant of Downward Auditor Switching. This study examines the factors that influence downward auditor switching in five ASEAN countries. Fixed effect logistic regression was used as analytical method. This study found that opinion shopping occurred in ASEAN, especially in distress companies. Companies with complex businesses will retain the Big Four auditors to reduce complexity and audit costs. Audit and public committees serve as guardians of auditor quality. On the other hand, shareholders failed to maintain audit quality. It indicates that there is entrenchment effect in auditor switching.

  13. Health inequality - determinants and policies

    DEFF Research Database (Denmark)

    Diderichsen, Finn; Andersen, Ingelise; Manual, Celie

    2012-01-01

    The review ”Health inequality – determinants and policies” identifies key-areas to be addressed with the aim to reduce the social inequality in health. The general life expectancy has steadily been increasing, but the data reveals marked social inequalities in health as well as life expectancy....... The review seeks to identify the causes of this social inequality. The analysis finds 12 areas of great importance for the inequality in health. This is i.e. early child development, schooling and education, the health behavior of the population, and the role of the health system. Within each of the 12 areas...

  14. Structure determination of enterovirus 71

    Energy Technology Data Exchange (ETDEWEB)

    Plevka, Pavel; Perera, Rushika; Cardosa, Jane; Kuhn, Richard J.; Rossmann, Michael G. (Purdue); (Sentinext)

    2013-02-20

    Enterovirus 71 is a picornavirus that causes hand, foot and mouth disease but may induce fatal neurological illness in infants and young children. Enterovirus 71 crystallized in a body-centered orthorhombic space group with two particles in general orientations in the crystallographic asymmetric unit. Determination of the particle orientations required that the locked rotation function excluded the twofold symmetry axes from the set of icosahedral symmetry operators. This avoided the occurrence of misleading high rotation-function values produced by the alignment of icosahedral and crystallographic twofold axes. Once the orientations and positions of the particles had been established, the structure was solved by molecular replacement and phase extension.

  15. New frontiers in PDF determination

    CERN Multimedia

    CERN. Geneva

    2016-01-01

    Parton Distribution Functions (PDFs) are a crucial input at the LHC, their uncertainty often being the limiting factor in the accuracy of theoretical predictions. At the same time the LHC is delivering a number of precise measurements that have the potential to greatly constrain these functions. I will give an overview on the theory behind and on the state of the art of PDF determination. I will then mention the new theoretical and methodological challenges in modern PDF fits and explore the precision frontiers opened by the accuracy of the LHC data.

  16. Sociocultural determinants of induced abortion.

    Science.gov (United States)

    Korejo, Razia; Noorani, Khurshid Jehan; Bhutta, Shereen

    2003-05-01

    To determine the frequency of induced abortion and identify the role of sociocultural factors contributing to termination of pregnancy and associated morbidity and mortality in hospital setting. Prospective observational study. The study was conducted in the Department of Obstetrics and Gynaecology, Jinnah Postgraduate Medical Centre, Karachi from January 1999 to June 2001. The patients who were admitted for induced abortion were interviewed in privacy. On condition of anonymity they were asked about the age, parity, family setup and relationships, with particular emphasis on sociocultural reasons and factors contributing to induction of abortion. Details of status of abortionist and methods used for termination of pregnancy, the resulting complications and their severity were recorded. Out of total admissions, 57(2.35%) gave history of induced abortion. All women belonged to low socioeconomic class and 59.6% of them were illiterate. Forty-three (75.5%) of these women had never practiced contraception. Twenty-four (42%) were grandmultiparae and did not want more children. In 29 women (50.9%) the decision for abortion had been supported by the husband. In 25 women (43.8%) abortion was carried out by Daiyan (traditional midwives). Serious complications like uterine perforation with or without bowel injury were encountered in 25 (43.8%) of these women. During the study period illegally induced abortion accounted for 6 (10.5%) maternal deaths. Prevalence of poverty, illiteracy, grand multiparity and non-practice of contraception are strong determinants of induced abortion.

  17. Green investment: Trends and determinants

    International Nuclear Information System (INIS)

    Eyraud, Luc; Clements, Benedict; Wane, Abdoul

    2013-01-01

    This paper fills a gap in the macroeconomic literature on renewable sources of energy. It offers a definition of green investment and analyzes the trends and determinants of this investment over the last decade for 35 advanced and emerging countries. We use a new multi-country historical dataset and find that green investment has become a key driver of the energy sector and that its rapid growth is now mostly driven by China. Our econometric results suggest that green investment is boosted by economic growth, a sound financial system conducive to low interest rates, and high fuel prices. We also find that some policy interventions, such as the introduction of carbon pricing schemes or “feed-in-tariffs,” which require use of “green” energy, have a positive and significant impact on green investment. Other interventions, such as biofuel support, do not appear to be associated with higher green investment. - Highlights: • We offer a definition of green investment and review its trend since 2000. • We analyze its determinants from both theoretical and empirical perspectives. • Green investment is boosted by economic growth, interest rates, and fuel prices. • Feed-in-tariffs and carbon pricing schemes impact positively green investment

  18. Determination of the neutron mass

    International Nuclear Information System (INIS)

    Amador V, P.; Chacon R, A.; Arcos P, A.; Rodriguez N, S.; Pinedo S, A.; Vega C, H.R.

    2005-01-01

    The binding energy of the deuteron was measured and it was determined the neutron mass starting from the nuclear reaction, 1 0 n + 1 1 H → 2 1 D + γ. The produced photon is soon a gamma ray that is emitted when the hydrogen captures a thermal neutron. The photon energy was measured using two spectrometric systems for gamma rays. A system with a detector of NaI(TI) of 3'' x 3'' and the other one with a High-purity Germanium detector. The first detector has a bigger efficiency and a smaller resolution in comparison with the second detector. The energy of the measured photon is the binding energy of the deuteron. With the measurement of the photon energy and the masses of the proton and of the deuterium it was determined the neutron mass. The value of the mass obtained with both systems it was compared with the value reported in the literature. The nuclear reaction was induced in a volume of paraffin that it was bombing with a source 239 PuBe whose activity is of 3.7 x 10 10 Bq. (Author)

  19. Emergent evolutionism, determinism and unpredictability.

    Science.gov (United States)

    Sartenaer, Olivier

    2015-06-01

    The fact that there exist in nature thoroughly deterministic systems whose future behavior cannot be predicted, no matter how advanced or fined-tune our cognitive and technical abilities turn out to be, has been well established over the last decades or so, essentially in the light of two different theoretical frameworks, namely chaos theory and (some deterministic interpretation of) quantum mechanics. The prime objective of this paper is to show that there actually exists an alternative strategy to ground the divorce between determinism and predictability, a way that is older than-and conceptually independent from-chaos theory and quantum mechanics, and which has not received much attention in the recent philosophical literature about determinism. This forgotten strategy-embedded in the doctrine called "emergent evolutionism"-is nonetheless far from being a mere historical curiosity that should only draw the attention of philosophers out of their concern for comprehensiveness. It has been indeed recently revived in the works of respected scientists. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. The determinants of food choice.

    Science.gov (United States)

    Leng, Gareth; Adan, Roger A H; Belot, Michele; Brunstrom, Jeffrey M; de Graaf, Kees; Dickson, Suzanne L; Hare, Todd; Maier, Silvia; Menzies, John; Preissl, Hubert; Reisch, Lucia A; Rogers, Peter J; Smeets, Paul A M

    2017-08-01

    Health nudge interventions to steer people into healthier lifestyles are increasingly applied by governments worldwide, and it is natural to look to such approaches to improve health by altering what people choose to eat. However, to produce policy recommendations that are likely to be effective, we need to be able to make valid predictions about the consequences of proposed interventions, and for this, we need a better understanding of the determinants of food choice. These determinants include dietary components (e.g. highly palatable foods and alcohol), but also diverse cultural and social pressures, cognitive-affective factors (perceived stress, health attitude, anxiety and depression), and familial, genetic and epigenetic influences on personality characteristics. In addition, our choices are influenced by an array of physiological mechanisms, including signals to the brain from the gastrointestinal tract and adipose tissue, which affect not only our hunger and satiety but also our motivation to eat particular nutrients, and the reward we experience from eating. Thus, to develop the evidence base necessary for effective policies, we need to build bridges across different levels of knowledge and understanding. This requires experimental models that can fill in the gaps in our understanding that are needed to inform policy, translational models that connect mechanistic understanding from laboratory studies to the real life human condition, and formal models that encapsulate scientific knowledge from diverse disciplines, and which embed understanding in a way that enables policy-relevant predictions to be made. Here we review recent developments in these areas.

  1. Sociocultural determinants of induced abortion

    International Nuclear Information System (INIS)

    Korejo, R.; Noorani, K.J.; Bhutta, S.

    2003-01-01

    Objective: To determine the frequency of induced abortion and identity the role of sociocultural factors contributing to termination of pregnancy and associated morbidity and mortality in hospital setting. Subjects and Methods: The patients who were admitted for induced abortion were interviewed in privacy. On condition of anonymity they were asked about the age, parity, family setup and relationships, with particular emphasis on sociocultural reasons and factors contributing to induction of abortion. Details of status of abortionist and methods used for termination of pregnancy, the resulting complications and their severity were recorded. Results: Out of total admissions, 57(2.35%) gave history of induced abortion. All women belonged to low socioeconomic class and 59.6% of them were illiterate. Forty-three (75.5%) of these women had never practiced concentration. Twenty-four (42%) were grandmultiparae and did not want more children. In 29 women (50.9%) the decision for abortion had been supported by the husband. In 25 (43.8%) abortion was carried out by Daiyan (traditional midwives). Serious complications like uterine perforation with or without bowel injury were encouraged in 25 (43.8%) of these women. During the study period illegally induced abortion accounted for 6 (10.5%) maternal deaths. Conclusion: Prevalence of poverty, illiteracy, grand multiparity and non-practice of contraception are strong determinants of induced abortion. (author)

  2. 42 CFR 405.803 - Initial determination.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false Initial determination. 405.803 Section 405.803....803 Initial determination. (a) Carriers make initial determinations regarding claims for benefits under Medicare Part B. (b) An initial determination for purposes of this subpart includes determinations...

  3. 14 CFR 314.16 - Final determination.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Final determination. 314.16 Section 314.16... REGULATIONS EMPLOYEE PROTECTION PROGRAM Determination of Qualifying Dislocation § 314.16 Final determination... determination and, within 3 business days after the determination, serve a copy of the order on the persons...

  4. 42 CFR 405.715 - Reconsidered determination.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false Reconsidered determination. 405.715 Section 405.715... Part A § 405.715 Reconsidered determination. (a) In reconsidering an initial determination, the CMS shall review such initial determination, the evidence and findings upon which such determination was...

  5. Chandra Independently Determines Hubble Constant

    Science.gov (United States)

    2006-08-01

    A critically important number that specifies the expansion rate of the Universe, the so-called Hubble constant, has been independently determined using NASA's Chandra X-ray Observatory. This new value matches recent measurements using other methods and extends their validity to greater distances, thus allowing astronomers to probe earlier epochs in the evolution of the Universe. "The reason this result is so significant is that we need the Hubble constant to tell us the size of the Universe, its age, and how much matter it contains," said Max Bonamente from the University of Alabama in Huntsville and NASA's Marshall Space Flight Center (MSFC) in Huntsville, Ala., lead author on the paper describing the results. "Astronomers absolutely need to trust this number because we use it for countless calculations." Illustration of Sunyaev-Zeldovich Effect Illustration of Sunyaev-Zeldovich Effect The Hubble constant is calculated by measuring the speed at which objects are moving away from us and dividing by their distance. Most of the previous attempts to determine the Hubble constant have involved using a multi-step, or distance ladder, approach in which the distance to nearby galaxies is used as the basis for determining greater distances. The most common approach has been to use a well-studied type of pulsating star known as a Cepheid variable, in conjunction with more distant supernovae to trace distances across the Universe. Scientists using this method and observations from the Hubble Space Telescope were able to measure the Hubble constant to within 10%. However, only independent checks would give them the confidence they desired, considering that much of our understanding of the Universe hangs in the balance. Chandra X-ray Image of MACS J1149.5+223 Chandra X-ray Image of MACS J1149.5+223 By combining X-ray data from Chandra with radio observations of galaxy clusters, the team determined the distances to 38 galaxy clusters ranging from 1.4 billion to 9.3 billion

  6. Determinants of Critical Infrastructure Resources

    Directory of Open Access Journals (Sweden)

    Ostrowska Teresa

    2017-12-01

    Full Text Available This article is devoted to the issue of how resources are interpreted in the form of technology reactors that, as a result of unexpected circumstances, turn into pyramidal or avalanche threat dynamics. Counteracting such catastrophic, terrorist, or war situations cannot begin in the face of mass casualties or significant material losses that will require reconstruction and the work of many generations. The decisive factor is the correct long-term operation and management of the economy. The starting point of this article is the concept of resource and structural-functional relationships of resources and all their possible interpretations consistent with the functionalities they play in the human environment, human aggregates, and whole nations. The aim is to draw the reader's attention to the importance (semiotics of qualitative specifications and dynamically changing determinants contained in the material and structural-functional properties of the resources and their channel (information communication.

  7. Determinants of Polish public debt

    Directory of Open Access Journals (Sweden)

    Tomasz Stryjewski

    2011-12-01

    Full Text Available The crisis, which had its beginning in 2007, turned into the debt crisis of the countries. The examples of Greece, Ireland, Iceland or Spain showed the category of public debt in a new light. Poland, at the turn of 2010/2011 also achieved the upper level of public debt acceptable by the law. In the present situation of the European Union countries being in debt, and even insolvent, the situation in Poland becomes riskier. This article attempts at an empirical verification of the determinants of Polish public debt within 95 months (the data link with the period of time from January 2003 to November 2010. The verification of the main factors which cause the formation of public debt takes place by means of an appropriately verified econometric model.

  8. Extractive spectrophotometric determination of thorium

    International Nuclear Information System (INIS)

    Venkatesan, M.; Gopalakrishnan, V.; Ramanujam, A.; Nadkarni, M.N.

    1981-01-01

    An extractive spectrophotometric method has been standardized for the analysis of 0.2 to 1.6 milligrams of thorium present in nitric acid solutions. The method involves the extraction of thorium from nitric acid solutions into 0.5 M thenoyl trifluoro acetone (HTTA) in benzene and its direct estimation from the organic extract by spectrophotometry as Thoron colour complex. In this method, interference due to iron upto 5 milligrams can be suppressed by adding ascorbic acid in the ratio of 1:2 prior to HTTA extraction. Uranium(VI) does not interefere even when present in 2000 times the amount of thorium. Plutonium and cerium do not interfere at one milligram level whereas zirconium interferes in this method. The overall error variation and precision of this method has been determined to be +- 3.5%. (author)

  9. Determining chiral couplings at NLO

    International Nuclear Information System (INIS)

    Rosell, Ignasi

    2007-01-01

    We present a general method that allows to estimate the low-energy constants of Chiral Perturbation Theory up to next-to-leading corrections in the 1/N C expansion, that is, keeping full control of the renormalization scale dependence. As a first step we have determined L 8 and C 38 , the couplings related to the difference of the two-point correlation functions of two scalar and pseudoscalar currents, L 8 r (μ 0 ) = (0.6±0.4)·10 -3 and C 38 r (μ 0 ) = (2±6)·10 -6 , with μ 0 0.77 GeV. As in many effective approaches, one of the main ingredients of this method is the matching procedure: some comments related to this topic are presented here

  10. Perception determinants in learning mathematics

    Science.gov (United States)

    Mokhtar, Siti Fairus; Ali, Noor Rasidah; Rashid, Nurazlina Abdul

    2015-05-01

    This article described a statistical study of students' perception in mathematics. The objective of this study is to identify factors related to perception about learning mathematics among non mathematics' student. This study also determined the relationship between of these factors among non mathematics' student. 43 items questionnaires were distributed to one hundred students in UiTM Kedah who enrolled in the Business Mathematics course. These items were measured by using a semantic scale with the following anchors: 1 = strongly disagree to 7 = strongly agree. A factor analysis of respondents were identified into five factors that influencing the students' perception in mathematics. In my study, factors identified were attitude, interest, role of the teacher, role of peers and usefulness of mathematics that may relate to the perception about learning mathematics among non mathematics' student.

  11. PUBLIC DEBT DETERMINANTS IN ALBANIA

    Directory of Open Access Journals (Sweden)

    Edlira Kalaja

    2015-10-01

    Full Text Available State budget is one of the most important instruments where the government reflects its future policies, priorities and commitments. Its reading in recent years clearly shows the increased size of public debt beyond the upper limit of 60% of GDP, in many countries including Albania. This fact constitutes analarming trend signaled even by many international financial institutions. However, the worldwide increasing levels of budget deficits and public debtsare not accidental. Through this article we aim to explore the relationships that exists between different determinants such as governance, social and economic variables that directly affect the size of public debt in Albania, where demographic factors are noted as the main contributors, followed by political systems along with various economic developments that the country has experienced in years.

  12. Gravity Probe B orbit determination

    International Nuclear Information System (INIS)

    Shestople, P; Ndili, A; Parkinson, B W; Small, H; Hanuschak, G

    2015-01-01

    The Gravity Probe B (GP-B) satellite was equipped with a pair of redundant Global Positioning System (GPS) receivers used to provide navigation solutions for real-time and post-processed orbit determination (OD), as well as to establish the relation between vehicle time and coordinated universal time. The receivers performed better than the real-time position requirement of 100 m rms per axis. Post-processed solutions indicated an rms position error of 2.5 m and an rms velocity error of 2.2 mm s −1 . Satellite laser ranging measurements provided independent verification of the GPS-derived GP-B orbit. We discuss the modifications and performance of the Trimble Advance Navigation System Vector III GPS receivers. We describe the GP-B precision orbit and detail the OD methodology, including ephemeris errors and the laser ranging measurements. (paper)

  13. Detecting determinism from point processes.

    Science.gov (United States)

    Andrzejak, Ralph G; Mormann, Florian; Kreuz, Thomas

    2014-12-01

    The detection of a nonrandom structure from experimental data can be crucial for the classification, understanding, and interpretation of the generating process. We here introduce a rank-based nonlinear predictability score to detect determinism from point process data. Thanks to its modular nature, this approach can be adapted to whatever signature in the data one considers indicative of deterministic structure. After validating our approach using point process signals from deterministic and stochastic model dynamics, we show an application to neuronal spike trains recorded in the brain of an epilepsy patient. While we illustrate our approach in the context of temporal point processes, it can be readily applied to spatial point processes as well.

  14. Experimental determination of Ramsey numbers.

    Science.gov (United States)

    Bian, Zhengbing; Chudak, Fabian; Macready, William G; Clark, Lane; Gaitan, Frank

    2013-09-27

    Ramsey theory is a highly active research area in mathematics that studies the emergence of order in large disordered structures. Ramsey numbers mark the threshold at which order first appears and are extremely difficult to calculate due to their explosive rate of growth. Recently, an algorithm that can be implemented using adiabatic quantum evolution has been proposed that calculates the two-color Ramsey numbers R(m,n). Here we present results of an experimental implementation of this algorithm and show that it correctly determines the Ramsey numbers R(3,3) and R(m,2) for 4≤m≤8. The R(8,2) computation used 84 qubits of which 28 were computational qubits. This computation is the largest experimental implementation of a scientifically meaningful adiabatic evolution algorithm that has been done to date.

  15. Determination of chitin in Claviceps

    Energy Technology Data Exchange (ETDEWEB)

    Schmauder, H P; Groeger, D [Akademie der Wissenschaften der DDR, Halle/Saale. Inst. fuer Biochemie der Pflanzen

    1978-01-01

    Preparations rich in chitin obtained from the cell walls of ergot fungi were studied by X-ray diffraction and IR-techniques. During the course of fermentation, the yield of chitin was determined using a modified procedure according to Ride and Drysdale (1972). A saprophytic ergotoxine-producing Claviceps purpurea strain (Pepty 695) was found to contain 7-9 ..mu..g glucosamine/mg dry weight of the mycelium in contrast to 3-5 ..mu..g glucosamine/mg dry weight of a non-alkaloid producing C. purpurea strain (PUR 212). There was no remarkable fluctuation of the glucosamine content in strain Pepty 695 during the course of fermentation.

  16. Determination of Human Hemoglobin Derivatives.

    Science.gov (United States)

    Attia, Atef M M; Ibrahim, Fatma A A; Abd El-Latif, Noha A; Aziz, Samir W; Abdelmottaleb Moussa, Sherif A; Elalfy, Mohsen S

    2015-01-01

    The levels of the inactive hemoglobin (Hb) pigments [such as methemoglobin (metHb), carboxyhemoglobin (HbCO) and sulfohemoglobin (SHb)] and the active Hb [in the oxyhemoglobin (oxyHb) form] as well as the blood Hb concentration in healthy non pregnant female volunteers were determined using a newly developed multi-component spectrophotometric method. The results of this method revealed values of SHb% in the range (0.0727-0.370%), metHb% (0.43-1.0%), HbCO% (0.4-1.52%) and oxyHb% (97.06-98.62%). Furthermore, the results of this method revealed values of blood Hb concentration in the range (12.608-15.777 g/dL). The method is highly sensitive, accurate and reproducible.

  17. DETERMINANTS OF POVERTY IN ROMANIA

    Directory of Open Access Journals (Sweden)

    CLAUDIA ANDREEA UREAN

    2017-08-01

    Full Text Available Romania is one of the poorest countries in Europe. The purpose of this investigation is to determine which factors influence the magnitude of this socio-economic phenomenon. Current availability of data from National Institute of Statistics ensures our sample. We apply a panel data analysis of regional development: North-East, SouthEast, South, South-West, West, North-West, Centre and Bucharest-Ilfov to understand how Romania can reduce poverty. The authors found a direct link between relative poverty rate and education. In addition, the negative relationship between poverty and pensioners shows the importance of a good government policies. In this context, we propose to focus our attention on the needs of people. Education can be an important determinat of national development, on the other slide, educated people are more willing to understand the role of pension system.

  18. Neptunium determination in PUREX process

    International Nuclear Information System (INIS)

    Rawat, Neetika; Kar, Aishwarya S.; Tomar, B.S.; Pandey, M.P.; Umadevi, K.

    2016-10-01

    237 Np is one of the most important minor actinides present in nuclear spent fuel both from environmental and application point of view. The routing of neptunium to the particular stream of PUREX process is necessary for its separation and purification as 237 Np is the target nuclide for production of 238 Pu. The routing of neptunium to a particular PUREX stream will also help in better nuclear waste management, which in turn, will impart less bearing on the environment considering its long half life, alpha emitting properties and mobile nature. In order to route Neptunium to a particular stream of PUREX process, it is imperative to understand the distribution of neptunium in various process streams. Owing to high dose of actual samples, the neptunium distribution was studied using 239 Np tracer by simulating actual column conditions of PUREX streams in lab scale. The present study deals with neptunium determination in actual PUREX streams samples also. (author)

  19. Genetic modification and genetic determinism

    Directory of Open Access Journals (Sweden)

    Vorhaus Daniel B

    2006-06-01

    Full Text Available Abstract In this article we examine four objections to the genetic modification of human beings: the freedom argument, the giftedness argument, the authenticity argument, and the uniqueness argument. We then demonstrate that each of these arguments against genetic modification assumes a strong version of genetic determinism. Since these strong deterministic assumptions are false, the arguments against genetic modification, which assume and depend upon these assumptions, are therefore unsound. Serious discussion of the morality of genetic modification, and the development of sound science policy, should be driven by arguments that address the actual consequences of genetic modification for individuals and society, not by ones propped up by false or misleading biological assumptions.

  20. Determination of phenol in tar

    Energy Technology Data Exchange (ETDEWEB)

    Dierichs, A; Heinichen, G

    1955-01-01

    During low-temperature carbonization of lignite, the phenols and other oxygenated compounds appear both in the aqueous-process liquor and in the tar. Measurements of these oxygenated components resulting from low-temperature carbonization may serve as a parameter for the classification of lignites. However, such measurements are complicated by the instability of the tar and the complex nature of some of the acidic substances. Difficulties with the previous methods of analysis are reviewed. The present method outlines separation of aqueous-process liquor from lignite tar in a Fischer retort, followed by determination of phenols and fatty acids in the tar phase. The jacketed tar receiver is washed with 300 milliliter xylol and treated with aqueous caustic washes. Neutral oils are separated from the aqueous alkali solution. It is then extracted with ether and finally acidified with HCl. Solids are filtered off, and phenols and fatty acids are separated by Na/sub 2/CO/sub 3/ solution.

  1. Concepts in sample size determination

    Directory of Open Access Journals (Sweden)

    Umadevi K Rao

    2012-01-01

    Full Text Available Investigators involved in clinical, epidemiological or translational research, have the drive to publish their results so that they can extrapolate their findings to the population. This begins with the preliminary step of deciding the topic to be studied, the subjects and the type of study design. In this context, the researcher must determine how many subjects would be required for the proposed study. Thus, the number of individuals to be included in the study, i.e., the sample size is an important consideration in the design of many clinical studies. The sample size determination should be based on the difference in the outcome between the two groups studied as in an analytical study, as well as on the accepted p value for statistical significance and the required statistical power to test a hypothesis. The accepted risk of type I error or alpha value, which by convention is set at the 0.05 level in biomedical research defines the cutoff point at which the p value obtained in the study is judged as significant or not. The power in clinical research is the likelihood of finding a statistically significant result when it exists and is typically set to >80%. This is necessary since the most rigorously executed studies may fail to answer the research question if the sample size is too small. Alternatively, a study with too large a sample size will be difficult and will result in waste of time and resources. Thus, the goal of sample size planning is to estimate an appropriate number of subjects for a given study design. This article describes the concepts in estimating the sample size.

  2. Complexometric determination, Part II: Complexometric determination of Cu2+-ions

    Directory of Open Access Journals (Sweden)

    Rajković Miloš B.

    2002-01-01

    Full Text Available A copper-selective electrode of the coated wire type based on sulphidized copper wire was applied successfully for determining Cu(II ions by complexometric titration with the disodium salt of EDTA (complexon III. By the formation of internal complex compounds with the Cu(II ion, the copper concentration in the solution decreases, and all this is followed by a change of potential of the indicator system Cu-DWISE (or Cu-EDWISE/SCE. At the terminal point of titration, when all the Cu(II ions are already utilized for the formation of the complex with EDTA, there occurs a steep rise of potential, thus enabling us, through the first or second derivative to note the quantity of copper that is present in the solution. Copper-selective electrode showed a responsivity towards titration with EDTA as a complexing agent, with the absence of "fatigue" due to a great number of repeated measurings. Errors occurring during quantitative measurements were more a characteristic of the overall procedure which involve, because of the impossibility of the complete absence of subjectivity, a constant error, and the reproducibility of the results confirmed this fact. The disodium salt of EDTA appeared as a very efficient titrant in all titrations and with various concentrations ot Cu(II ions in the solution, with somewhat weaker response at lower concentrations in the solution.

  3. Determinants of adolescent fertility in Ethiopia

    African Journals Online (AJOL)

    Bernt Lindtjorn

    demographic and economic determinants whereas Bongaarts model was used to determine proximate determinants fertility. ... Organization defines the age group of 10-19 and 15-24 ..... In urban areas, 24% of marital fertility was prevented.

  4. Determinants of female sexual orgasms

    Science.gov (United States)

    Kontula, Osmo; Miettinen, Anneli

    2016-01-01

    Background The pursuit of sexual pleasure is a key motivating factor in sexual activity. Many things can stand in the way of sexual orgasms and enjoyment, particularly among women. These are essential issues of sexual well-being and gender equality. Objective This study presents long-term trends and determinants of female orgasms in Finland. The aim is to analyze the roles of factors such as the personal importance of orgasms, sexual desire, masturbation, clitoral and vaginal stimulation, sexual self-esteem, communication with partner, and partner’s sexual techniques. Design In Finland, five national sex surveys that are based on random samples from the central population register have been conducted. They are representative of the total population within the age range of 18–54 years in 1971 (N=2,152), 18–74 years in 1992 (N=2,250), 18–81 years in 1999 (N=1,496), 18–74 years in 2007 (N=2,590), and 18–79 years in 2015 (N=2,150). Another dataset of 2,049 women in the age group of 18–70 years was collected in 2015 via a national Internet panel. Results Contrary to expectations, women did not have orgasms that are more frequent by increasing their experience and practice of masturbation, or by experimenting with different partners in their lifetime. The keys to their more frequent orgasms lay in mental and relationship factors. These factors and capacities included orgasm importance, sexual desire, sexual self-esteem, and openness of sexual communication with partners. Women valued their partner’s orgasm more than their own. In addition, positive determinants were the ability to concentrate, mutual sexual initiations, and partner’s good sexual techniques. A relationship that felt good and worked well emotionally, and where sex was approached openly and appreciatively, promoted orgasms. Conclusion The findings indicate that women differ greatly from one another in terms of their tendency and capacity to experience orgasms. The improvements in gender

  5. Determinants of female sexual orgasms

    Directory of Open Access Journals (Sweden)

    Osmo Kontula

    2016-10-01

    Full Text Available Background: The pursuit of sexual pleasure is a key motivating factor in sexual activity. Many things can stand in the way of sexual orgasms and enjoyment, particularly among women. These are essential issues of sexual well-being and gender equality. Objective: This study presents long-term trends and determinants of female orgasms in Finland. The aim is to analyze the roles of factors such as the personal importance of orgasms, sexual desire, masturbation, clitoral and vaginal stimulation, sexual self-esteem, communication with partner, and partner’s sexual techniques. Design: In Finland, five national sex surveys that are based on random samples from the central population register have been conducted. They are representative of the total population within the age range of 18–54 years in 1971 (N=2,152, 18–74 years in 1992 (N=2,250, 18–81 years in 1999 (N=1,496, 18–74 years in 2007 (N=2,590, and 18–79 years in 2015 (N=2,150. Another dataset of 2,049 women in the age group of 18–70 years was collected in 2015 via a national Internet panel. Results: Contrary to expectations, women did not have orgasms that are more frequent by increasing their experience and practice of masturbation, or by experimenting with different partners in their lifetime. The keys to their more frequent orgasms lay in mental and relationship factors. These factors and capacities included orgasm importance, sexual desire, sexual self-esteem, and openness of sexual communication with partners. Women valued their partner’s orgasm more than their own. In addition, positive determinants were the ability to concentrate, mutual sexual initiations, and partner’s good sexual techniques. A relationship that felt good and worked well emotionally, and where sex was approached openly and appreciatively, promoted orgasms. Conclusion: The findings indicate that women differ greatly from one another in terms of their tendency and capacity to experience orgasms. The

  6. Determinants of the company value

    Directory of Open Access Journals (Sweden)

    Kamila Růžičková

    2011-01-01

    Full Text Available Today, there are many conceptions involving creation of the company value, as it is the main objective for the owners. However, there are still many companies interested primarily in the different company’s objectives and enhance its competitive position differently. The aim of the paper is to present and analyze the viewpoints of Czech and foreign specialists on the issue of company value creation. The paper provides the determination of factors positively influencing the company value, the description of their characteristics, and on the basis of a detailed academic discussion proposes conclusions. Attention is paid especially to the value drivers which are not recorded in the financial documents.The introduction of the paper gives a brief overview of the topic. The paper is divided into three main parts. The first part introduces the effective cost management. It clarifies the concept of the managerial accounting and explains its contribution to the creation of the company value. The second part deals with the external relationships of the company. It focuses on the buyer-supplier relationships and offers the detailed perspective on the specific issue of the agricultural companies and their competitiveness in relation to the land leases. The third part concentrates on the internal company environment, namely on the human capital potential and its effects on the value of the company. In the concluding part, the findings are summarized. Based on the results, the figure describing the determinants and generators of the company value is formed. This figure can be considered a systematic procedure how to create a company value.All findings are supported with the literature review e.g. Armstrong (2007, Fibírová and Šoljaková (2005, Marinič (2008, Petřík (2007 and Porter (2004. Within the paper elaboration, the analysis and synthesis as scientific methods were used for explanation of the experts’ points of view and then summed up as the

  7. Checkpoint-dependent RNR induction promotes fork restart after replicative stress.

    Science.gov (United States)

    Morafraile, Esther C; Diffley, John F X; Tercero, José Antonio; Segurado, Mónica

    2015-01-20

    The checkpoint kinase Rad53 is crucial to regulate DNA replication in the presence of replicative stress. Under conditions that interfere with the progression of replication forks, Rad53 prevents Exo1-dependent fork degradation. However, although EXO1 deletion avoids fork degradation in rad53 mutants, it does not suppress their sensitivity to the ribonucleotide reductase (RNR) inhibitor hydroxyurea (HU). In this case, the inability to restart stalled forks is likely to account for the lethality of rad53 mutant cells after replication blocks. Here we show that Rad53 regulates replication restart through the checkpoint-dependent transcriptional response, and more specifically, through RNR induction. Thus, in addition to preventing fork degradation, Rad53 prevents cell death in the presence of HU by regulating RNR-expression and localization. When RNR is induced in the absence of Exo1 and RNR negative regulators, cell viability of rad53 mutants treated with HU is increased and the ability of replication forks to restart after replicative stress is restored.

  8. Significant biases affecting abundance determinations

    Science.gov (United States)

    Wesson, Roger

    2015-08-01

    I have developed two highly efficient codes to automate analyses of emission line nebulae. The tools place particular emphasis on the propagation of uncertainties. The first tool, ALFA, uses a genetic algorithm to rapidly optimise the parameters of gaussian fits to line profiles. It can fit emission line spectra of arbitrary resolution, wavelength range and depth, with no user input at all. It is well suited to highly multiplexed spectroscopy such as that now being carried out with instruments such as MUSE at the VLT. The second tool, NEAT, carries out a full analysis of emission line fluxes, robustly propagating uncertainties using a Monte Carlo technique.Using these tools, I have found that considerable biases can be introduced into abundance determinations if the uncertainty distribution of emission lines is not well characterised. For weak lines, normally distributed uncertainties are generally assumed, though it is incorrect to do so, and significant biases can result. I discuss observational evidence of these biases. The two new codes contain routines to correctly characterise the probability distributions, giving more reliable results in analyses of emission line nebulae.

  9. Neuronal factors determining high intelligence.

    Science.gov (United States)

    Dicke, Ursula; Roth, Gerhard

    2016-01-05

    Many attempts have been made to correlate degrees of both animal and human intelligence with brain properties. With respect to mammals, a much-discussed trait concerns absolute and relative brain size, either uncorrected or corrected for body size. However, the correlation of both with degrees of intelligence yields large inconsistencies, because although they are regarded as the most intelligent mammals, monkeys and apes, including humans, have neither the absolutely nor the relatively largest brains. The best fit between brain traits and degrees of intelligence among mammals is reached by a combination of the number of cortical neurons, neuron packing density, interneuronal distance and axonal conduction velocity--factors that determine general information processing capacity (IPC), as reflected by general intelligence. The highest IPC is found in humans, followed by the great apes, Old World and New World monkeys. The IPC of cetaceans and elephants is much lower because of a thin cortex, low neuron packing density and low axonal conduction velocity. By contrast, corvid and psittacid birds have very small and densely packed pallial neurons and relatively many neurons, which, despite very small brain volumes, might explain their high intelligence. The evolution of a syntactical and grammatical language in humans most probably has served as an additional intelligence amplifier, which may have happened in songbirds and psittacids in a convergent manner. © 2015 The Author(s).

  10. Higgs mass determination in supersymmetry

    Energy Technology Data Exchange (ETDEWEB)

    Vega, Javier Pardo [Abdus Salam International Centre for Theoretical Physics, Strada Costiera 11, 34151, Trieste (Italy); SISSA International School for Advanced Studies and INFN Trieste, Via Bonomea 265, 34136, Trieste (Italy); Villadoro, Giovanni [Abdus Salam International Centre for Theoretical Physics, Strada Costiera 11, 34151, Trieste (Italy)

    2015-07-29

    We present the state-of-the-art of the effective field theory computation of the MSSM Higgs mass, improving the existing ones by including extra threshold corrections. We show that, with this approach, the theoretical uncertainty is within 1 GeV in most of the relevant parameter space. We confirm the smaller value of the Higgs mass found in the EFT computations, which implies a slightly heavier SUSY scale. We study the large tan β region, finding that sbottom thresholds might relax the upper bound on the scale of SUSY. We present SUSYHD, a fast computer code that computes the Higgs mass and its uncertainty for any SUSY scale, from the TeV to the Planck scale, even in Split SUSY, both in the (DR)-bar and in the on-shell schemes. Finally, we apply our results to derive bounds on some well motivated SUSY models, in particular we show how the value of the Higgs mass allows to determine the complete spectrum in minimal gauge mediation.

  11. Uranium determination in different compositions

    International Nuclear Information System (INIS)

    Bulyanitsa, L.S.; Ivanova, K.S.; Ryzhinskij, M.V.; Alekseeva, N.A.; Solntseva, L.F.; Shereshevskaya, I.I.

    1978-01-01

    For clarifying the suitability of two different methods of analysis for determining uranium without its previous purification, the analysis of uranium carbides (UC, UC 2 , UC - ZrC) and alloys (U - Al, U - Zr - Nb, U- Ti) has been carried out. Dissolution of the compositions examined was carried out either after previous calcining (UC, UC 2 ) or fusion with KHSO 4 (UC - ZrC), or in phosphoric acid (alloys). The first method, a variant of potentiometric titration, has been modified for small amounts of uranium. Titration was carried out on a semiautomatic titrating unit. The uranium amount per titration is about 4 to 5 mg. The second method of analysis is the coulombmetric titration at a constant current intensity. The quantity of uranium per titration was equal to 1 - 3 mg. The statistical processing of the results obtained was carried out by a dispersion analysis that allowed to reveal the influence of separate factors, such as method of analysis, type of composition, the non-uniformity of a sample, the enumerated factors influencing the dispersion of the analysis results. It has been shown that the both methods are equally suitable for analysis of the uranium compounds examined

  12. Microenvironment Determinants of Brain Metastasis

    Directory of Open Access Journals (Sweden)

    Zhang Chenyu

    2011-02-01

    Full Text Available Abstract Metastasis accounts for 90% of cancer-related mortality. Brain metastases generally present during the late stages in the natural history of cancer progression. Recent advances in cancer treatment and management have resulted in better control of systemic disease metastatic to organs other than the brain and improved patient survival. However, patients who experience recurrent disease manifest an increasing number of brain metastases, which are usually refractory to therapies. To meet the new challenges of controlling brain metastasis, the research community has been tackling the problem with novel experimental models and research tools, which have led to an improved understanding of brain metastasis. The time-tested "seed-and-soil" hypothesis of metastasis indicates that successful outgrowth of deadly metastatic tumors depends on permissible interactions between the metastatic cancer cells and the site-specific microenvironment in the host organs. Consistently, recent studies indicate that the brain, the major component of the central nervous system, has unique physiological features that can determine the outcome of metastatic tumor growth. The current review summarizes recent discoveries on these tumor-brain interactions, and the potential clinical implications these novel findings could have for the better treatment of patients with brain metastasis.

  13. Determinants of children's eating behavior.

    Science.gov (United States)

    Scaglioni, Silvia; Arrizza, Chiara; Vecchi, Fiammetta; Tedeschi, Sabrina

    2011-12-01

    Parents have a high degree of control over the environments and experiences of their children. Food preferences are shaped by a combination of genetic and environmental factors. This article is a review of current data on effective determinants of children's eating habits. The development of children's food preferences involves a complex interplay of genetic, familial, and environmental factors. There is evidence of a strong genetic influence on appetite traits in children, but environment plays an important role in modeling children's eating behaviors. Parents use a variety of strategies to influence children's eating habits, some of which are counterproductive. Overcontrol, restriction, pressure to eat, and a promise of rewards have negative effects on children's food acceptance. Parents' food preferences and eating behaviors provide an opportunity to model good eating habits. Satiety is closely related to diet composition, and foods with low energy density contribute to prevent overeating. Parents should be informed about the consequences of an unhealthy diet and lifestyle and motivated to change their nutritional habits. Parents should be the target of prevention programs because children model themselves on their parents' eating behaviors, lifestyles, eating-related attitudes, and dissatisfaction regarding body image. Pediatricians can have an important role in the prevention of diet-related diseases. Informed and motivated parents can become a model for children by offering a healthy, high-satiety, low-energy-dense diet and promoting self-regulation from the first years of life.

  14. Weapons barrel life cycle determination

    Directory of Open Access Journals (Sweden)

    Nebojša Pene Hristov

    2013-10-01

    Full Text Available This article describes the dynamic processes within the gun barrel during the firing process in exploitation. It generally defines the basic principles of constructing tube elements, and shows the distortion of the basic geometry of the tube interior due to wear as well as the impact it causes during exploitation. The article also defines basic empirical models as well as a model based on fracture mechanics for the calculation of a use-life of the barrel, and other elements essential for the safe use of the barrel as the basic weapon element. Erosion causes are analysed in order to control and reduce wear and prolong the lifetime of the gun barrel. It gives directions for the reparation of barrels with wasted resources. In conclusion, the most influential elements of tube wear are given as well as possible modifications of existing systems, primarily propellant charges, with a purpose of prolonging lifetime of gun barrels. The guidelines for a proper determination of the lifetime based on the barrel condition assessment are given as well. INTRODUCTION The barrel as the basic element of each weapon is described as well as the processes occurring during the firing that have impulsive character and are accompanied by large amounts of energy. The basic elements of barrel and itheir constructive characteristics are descibed. The relation between Internal ballistics, ie calculation of the propellant gas pressure in the firing process, and structural elements defined by the barrel material resistance is shown. In general, this part of the study explains the methodology of the gun barrel structural elements calculation, ie. barrel geometry, taking into account the degrees of safety in accordance with Military Standards.   TUBE WEAR AND DEFORMATIONS The weapon barrel gradually wears out during exploitation due to which it no longer satisfies the set requirements. It is considered that the barrel has experienced a lifetime when it fails to fulfill the

  15. [Sociodemographic determinants of women's health].

    Science.gov (United States)

    Ordonez Gomez, M

    1991-06-01

    This work correlates a series of variables influencing fertility, maternal-child health, and infant mortality from Colombia's 1990 Contraceptive Prevalence, Demography, and Health Survey for 13 regions of Colombia. Causes of death among women aged 15-49 years for 1989 are then examined, and an integrated health program developed by the Association for Family Welfare (PROFAMILIA) for lower income rural and semirural women is described as an example of a successful primary health care program. Colombia's total fertility rate declined from 7.0 in 1965 to 2.9 in 1990. The marital total fertility rate among some subgroups, however, still exceeds 5.0. Fertility is often higher in rural zones, among less educated women, and among those not employed outside the home. The major fertility determinants are family planning, nuptiality, and socioeconomic status, as well as infertility due to lactation and abortion. Family size ideals also play a role. The highest fertility in Colombia today is in the departments of the Atlantic region, in Choco and the Pacific Coast, and in the subregion of the departments of Tolima-Huila and Caqueta. According to the 1990 survey, 66% of women currently in union used a contraceptive method. 62.3% of women in Cali and 61.8% in Bogota used modern methods, compared to only 41% in Tolima-Huila-Caqueta and 43% in Guajira-Magdalena. About 52% of fertile-aged women in Colombia are currently in union. The region of highest fertility have the lowest ages at 1st sexual relations, 1st union, and birth of 1st child. The 1st birth occurred at an average age of 24 years in Antioquia compared to 20 years in the Atlantic Coast. The regions of highest fertility are also those with the greatest proportion of women in union: 60% in the Atlantic region and in Tolima-Huila-Caqueta but only 46% in Antioquia. Socioeconomic status is a major fertility determinant, working through education and accessibility of family planning services. The correlation between

  16. 49 CFR 107.209 - Determination.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false Determination. 107.209 Section 107.209... PROGRAM PROCEDURES Preemption Preemption Determinations § 107.209 Determination. (a) Upon consideration of the application and other relevant information received, the Chief Counsel issues a determination. (b...

  17. 36 CFR 223.36 - Volume determination.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Volume determination. 223.36... Volume determination. (a) Timber sale contracts may provide for volume determination by scaling... the contract or permit provides for the determination of volume by tree measurement and the timber has...

  18. 36 CFR 902.60 - Initial determination.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Initial determination. 902.60... INFORMATION ACT Time Limitations § 902.60 Initial determination. (a) An initial determination whether or not... workdays in accordance with § 902.62. (b) Upon making initial determination, the Administrative Officer...

  19. 42 CFR 405.810 - Review determination.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false Review determination. 405.810 Section 405.810....810 Review determination. Subject to the provisions of §§ 405.807 through 405.809, the carrier shall... determination affirming or revising in whole or in part the findings and determination in question. [39 FR 12097...

  20. 14 CFR 415.7 - Payload determination.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Payload determination. 415.7 Section 415.7... TRANSPORTATION LICENSING LAUNCH LICENSE General § 415.7 Payload determination. A payload determination is... determination. Either a launch license applicant or a payload owner or operator may request a review of its...