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Sample records for bystander chinese hamster

  1. Low doses of alpha particles do not induce sister chromatid exchanges in bystander Chinese hamster cells defective in homologous recombination

    Energy Technology Data Exchange (ETDEWEB)

    Nagasawa, H; Wilson, P F; Chen, D J; Thompson, L H; Bedford, J S; Little, J B

    2007-10-26

    We reported previously that the homologous recombinational repair (HRR)-deficient Chinese hamster mutant cell line irs3 (deficient in the Rad51 paralog Rad51C) showed only a 50% spontaneous frequency of sister chromatid exchange (SCE) as compared to parental wild-type V79 cells. Furthermore, when irradiated with very low doses of alpha particles, SCEs were not induced in irs3 cells, as compared to a prominent bystander effect observed in V79 cells (Nagasawa et al., Radiat. Res. 164, 141-147, 2005). In the present study, we examined additional Chinese hamster cell lines deficient in the Rad51 paralogs Rad51C, Rad51D, Xrcc2, and Xrcc3 as well as another essential HRR protein, Brca2. Spontaneous SCE frequencies in non-irradiated wild-type cell lines CHO, AA8 and V79 were 0.33 SCE/chromosome, whereas two Rad51C-deficient cell lines showed only 0.16 SCE/chromosome. Spontaneous SCE frequencies in cell lines defective in Rad51D, Xrcc2, Xrcc3, and Brca2 ranged from 0.23-0.33 SCE/chromosome, 0-30% lower than wild-type cells. SCEs were induced significantly 20-50% above spontaneous levels in wild-type cells exposed to a mean dose of 1.3 mGy of alpha particles (<1% of nuclei traversed by an alpha particle). However, induction of SCEs above spontaneous levels was minimal or absent after {alpha}-particle irradiation in all of the HRR-deficient cell lines. These data suggest that Brca2 and the Rad51 paralogs contribute to DNA damage repair processes induced in bystander cells (presumably oxidative damage repair in S-phase cells) following irradiation with very low doses of alpha particles.

  2. Proteomic Analysis of Chinese Hamster Ovary Cells

    DEFF Research Database (Denmark)

    Baycin-Hizal, Deniz; Tabb, David L.; Chaerkady, Raghothama;

    2012-01-01

    To complement the recent genomic sequencing of Chinese hamster ovary (CHO) cells, proteomic analysis was performed on CHO cells including the cellular proteome, secretome, and glycoproteome using tandem mass spectrometry (MS/MS) of multiple fractions obtained from gel electrophoresis, multidimens...

  3. Proteomic analysis of Chinese hamster ovary cells.

    Science.gov (United States)

    Baycin-Hizal, Deniz; Tabb, David L; Chaerkady, Raghothama; Chen, Lily; Lewis, Nathan E; Nagarajan, Harish; Sarkaria, Vishaldeep; Kumar, Amit; Wolozny, Daniel; Colao, Joe; Jacobson, Elena; Tian, Yuan; O'Meally, Robert N; Krag, Sharon S; Cole, Robert N; Palsson, Bernhard O; Zhang, Hui; Betenbaugh, Michael

    2012-11-01

    To complement the recent genomic sequencing of Chinese hamster ovary (CHO) cells, proteomic analysis was performed on CHO cells including the cellular proteome, secretome, and glycoproteome using tandem mass spectrometry (MS/MS) of multiple fractions obtained from gel electrophoresis, multidimensional liquid chromatography, and solid phase extraction of glycopeptides (SPEG). From the 120 different mass spectrometry analyses generating 682,097 MS/MS spectra, 93,548 unique peptide sequences were identified with at most 0.02 false discovery rate (FDR). A total of 6164 grouped proteins were identified from both glycoproteome and proteome analysis, representing an 8-fold increase in the number of proteins currently identified in the CHO proteome. Furthermore, this is the first proteomic study done using the CHO genome exclusively, which provides for more accurate identification of proteins. From this analysis, the CHO codon frequency was determined and found to be distinct from humans, which will facilitate expression of human proteins in CHO cells. Analysis of the combined proteomic and mRNA data sets indicated the enrichment of a number of pathways including protein processing and apoptosis but depletion of proteins involved in steroid hormone and glycosphingolipid metabolism. Five-hundred four of the detected proteins included N-acetylation modifications, and 1292 different proteins were observed to be N-glycosylated. This first large-scale proteomic analysis will enhance the knowledge base about CHO capabilities for recombinant expression and provide information useful in cell engineering efforts aimed at modifying CHO cellular functions. PMID:22971049

  4. Methods for modeling chinese hamster ovary (cho) cell metabolism

    DEFF Research Database (Denmark)

    2015-01-01

    for identifying a CHO cell line having a desired genetic trait, as well as for generating a desired CHO cell line having a genetic basis for a desired phenotype. Additionally, described herein are methods for constructing and analyzing in silico models of biological networks for CHO cells.......Embodiments of the present invention generally relate to the computational analysis and characterization biological networks at the cellular level in Chinese Hamster Ovary (CHO) cells. Based on computational methods utilizing a hamster reference genome, the invention provides methods...

  5. Genomic organization and expression of immunoglobulin genes in the Chinese hamster (Cricetulus griseus).

    Science.gov (United States)

    Qin, T; Zhu, H; Wang, D; Hao, H; Du, W

    2015-01-01

    In science, the hamsters are widely used as a model for studying the human diseases because they display many features like humans. The utility of the Chinese hamster as a biology model can be further enhanced by further characterization of the genes encoding components of the immune system. Here, we report the genomic organization and expression of the Chinese hamster immunoglobulin heavy and light chain genes. The Chinese hamster IgH locus contains 268 VH segments (132 potentially functional genes, 12 ORFs and 124 pseudogenes), 4 DH segments, 6 JH segments, four constant region genes (μ, γ, ε and α) and one reverse δ remnant fragment. The Igκ locus contains only a single Cκ gene, 4 Jκ segments and 48 Vκ segments (15 potentially functional genes and 33 pseudogenes), whereas the Igλ locus contains 4 Cλ genes, but only Cλ 3 and Cλ 4 each preceded by a Jλ gene segment. A total of 49 Vλ segments (39 potentially functional genes, 3 ORFs and 7 pseudogenes) were identified. Analysis of junctions of the recombined V(D)J transcripts reveals complex diversity in both expressed H and κ sequences, but the microhomology-directed VJ recombination obviously results in very limited diversity in the Chinese hamster λ gene despite more potential germline-encoded combinatorial diversity. This is the first study to make a comprehensive analysis of the Ig genes in the Chinese hamster, which provides insights into the Ig genes in placental mammals.

  6. Propranolol induced chromosomal aberrations in Chinese hamster ovary cell line

    Directory of Open Access Journals (Sweden)

    Mozhgan Sedigh-Ardekani

    2013-03-01

    Full Text Available Propranolol (PL, a non-selective beta-blocker, is a cardiovascular drug widely used to treat hypertension. The present study was concerned with assessing the cytogenetic effects of this drug on Chinese hamster ovary (CHO cell line. MTT assay was then carried out to determine the cytotoxicity index (IC50 of the drug. The IC50 value of PL was 0.43±0.02 mM. To investigate the clastogenic effects of the drug, chromatid and chromosome breaks and polyploidy in metaphases were analyzed. CHO cells were exposed to different concentrations of the drug (0.1, 0.2, 0.3, 0.4 mM for 24 hours. Considering that PL has liver metabolism, experiments were carried out in the presence and absence of the metabolic activation system (S9 mix. Mitomycin-C and sodium arsenite were used as positive controls. It was observed that in cells treated with different PL concentrations as 0.1, 0.2 and 0.3 mM, the frequency of chromatid and chromosome breaks as well as polyploidy increased when compared with untreated CHO cells. The addition of S9 mix significantly decreased the chromatid breaks, chromosome breaks and polyploidy compared to the treatment of PL alone. It is concluded that, PL causes chromatid and chromosome aberrations in CHO cell line and the metabolic activation system (S9 mix, playing an important role in drug cytotoxicity reduction.

  7. Existence of an Endogenous Glutamate and Aspartate Transporter in Chinese Hamster Ovary Cells

    Institute of Scientific and Technical Information of China (English)

    Xunhe JI; Yuhua JIN; Yaoyue CHEN; Chongyong LI; Lihe GUO

    2007-01-01

    Chinese hamster ovary cells show endogenous high-affinity Na+-dependent glutamate transport activity. This transport activity is kinetically similar to a glutamate transporter family strategically expressed in the central nervous system and is pharmacologically unlike glutamate transporter-1 or excitatory amino acid carrier 1. The cDNA of a glutamate/aspartate transporter (GLAST)-like transporter was obtained and analyzed. The deduced amino acid sequence showed high similarity to human, mouse, and rat GLAST. We concluded that a GLAST-like glutamate transporter exists in Chinese hamster ovary cells that might confer the endogenous high-affinity Na+-dependent glutamate transport activity evident in these cells.

  8. The genomic sequence of the Chinese hamster ovary (CHO)-K1 cell line

    DEFF Research Database (Denmark)

    Xu, Xun; Pan, Shengkai; Liu, Xin;

    2011-01-01

    Chinese hamster ovary (CHO)-derived cell lines are the preferred host cells for the production of therapeutic proteins. Here we present a draft genomic sequence of the CHO-K1 ancestral cell line. The assembly comprises 2.45 Gb of genomic sequence, with 24,383 predicted genes. We associate most of...

  9. Characterization of Chinese Hamster Ovary Cells Producing Coagulation Factor VIII Using Multi-omics Tools

    DEFF Research Database (Denmark)

    Kaas, Christian Schrøder

    The first public draft of a genome from Chinese hamster ovary (CHO) cells was published in 2011, an entire decade after the first draft of the human genome. This publication of a relevant CHO reference genome, in combination with the fact that the cost for DNA sequencing has dropped more than 10,...

  10. Toward genome-scale models of the Chinese hamster ovary cells: incentives, status and perspectives

    DEFF Research Database (Denmark)

    Kaas, Christian Schrøder; Fan, Yuzhou; Weilguny, Dietmar;

    2014-01-01

    Bioprocessing of the important Chinese hamster ovary (CHO) cell lines used for the production of biopharmaceuticals stands at the brink of several redefining events. In 2011, the field entered the genomics era, which has accelerated omics-based phenotyping of the cell lines. In this review we des...

  11. Induction of chromosome aberrations in Chinese hamster cells after heavy ion irradiation

    International Nuclear Information System (INIS)

    The induction of structural chromosome changes in V 79-Chinese hamster cells following heavy ion irradiation is studied. Asynchronous exponentially growing cells are exposed to the heavy ion beams at the Unilac, Darmstadt and the Ganil, Caen. The induction of chromosome aberrations was measured as a function of time after exposure. (orig./MG)

  12. Genomic landscapes of Chinese hamster ovary cell lines as revealed by the Cricetulus griseus draft genome

    DEFF Research Database (Denmark)

    Lewis, Nathan E; Liu, Xin; Li, Yuxiang;

    2013-01-01

    stymied by the lack of a unifying genomic resource for CHO cells. Here we report a 2.4-Gb draft genome sequence of a female Chinese hamster, Cricetulus griseus, harboring 24,044 genes. We also resequenced and analyzed the genomes of six CHO cell lines from the CHO-K1, DG44 and CHO-S lineages...

  13. Assignment of genes encoding metallothioneins I and II to Chinese hamster chromosomes 3. Evidence for the role of chromosome rearrangement in gene amplification

    Energy Technology Data Exchange (ETDEWEB)

    Stallings, R.L.; Munk, A.C.; Longmire, J.L.; Hildebrand, C.E.; Crawford, B.D.

    1984-12-01

    Cadmium resistant (Cd/sup r/) variants with coordinately amplified metallothionein I and II (MTI and MTII) genes have been derived from both Chinese hamster ovary and near-euploid Chinese hamster cell lines. Cytogenetic analyses of Cd/sup r/ variants consistently revealed breakage and rearrangement involving chromosome 3p. In situ hybridization with Chinese hamster MT-encoding cDNA probe localized amplified MT gene sequences near the translocation breakpoint involving chromosome 3p. These observations suggested that both functionally related, isometallothionein loci are linked on Chinese hamster chromosome 3. Southern blot analyses of DNAs isolated from a panel of Chinese hamster x mouse somatic cell hybrids which segregate hamster chromosomes confirmed that both MTI and MTII are located on chromosome 3. The authors speculate that rearrangement of chromosome 3p could be causally involved with the amplification of MT genes in Cd/sup r/ hamster cell lines. 34 references, 3 figures, 1 table.

  14. Complementation of a methotrexate uptake defect in Chinese hamster ovary cells by DNA-mediated gene transfer.

    OpenAIRE

    Underhill, T M; Flintoff, W F

    1989-01-01

    A methotrexate-resistant Chinese hamster ovary cell line deficient in methotrexate uptake has been complemented to methotrexate sensitivity by transfection with DNA isolated from either wild-type Chinese hamster ovary or human G2 cells. Primary and secondary transfectants regained the ability to take up methotrexate in a manner similar to that of wild-type cells, and in the case of those transfected with human DNA, to contain human-specific DNA sequences. The complementation by DNA-mediated g...

  15. Interspecific complementation between mouse and Chinese hamster cell mutants hypersensitive to ionizing radiation

    International Nuclear Information System (INIS)

    Interspecific and intraspecific hybrids were formed between mouse and Chinese hamster cell mutants hypersensitive to ionizing radiation and their radiosensitivities were examined. Chinese hamster cell mutants irs1, irs2 and irs3 and mouse mammary carcinoma cell mutants SX9 and SX10 have been found to belong to five different complementation groups. A radiosensitive mouse lymphoma cell line L5178Y-S has been demonstrated to be different from the X-ray sensitive mouse cell mutants M10 and LX830, both of which are derived from L5178Y cells, in their complementation groups. L5178Y-S is also distinct from SX9 and SX10. (author)

  16. Selection of mutant Chinese hamster ovary cells altered glycoproteins by means of tritiated fucose suicide.

    OpenAIRE

    Hirschberg, C B; Baker, R.M.; Perez, M.; Spencer, L A; Watson, D

    1981-01-01

    Mutant Chinese hamster ovary cells altered in glycoproteins have been isolated by selecting for ability to survive exposure to [6-3H]fucose. Mutagenized wild-type cells were permitted to incorporate [3H]fucose to approximately 1 cpm of trichloroacetic acid-insoluble radioactivity per cell and then frozen for several days to accumulate radiation damage. The overall viability of the population was reduced by 5- to 50-fold. Four consecutive selection cycles were carried out. The surviving cells ...

  17. Metabolic engineering of Chinese hamster ovary cells: Towards a bioengineered heparin

    OpenAIRE

    Baik, Jong Youn; Gasimli, Leyla; Bo YANG; Datta, Payel; Zhang, Fuming; Glass, Charles A.; Esko, Jeffrey D.; Linhardt, Robert J.; Sharfstein, Susan T.

    2012-01-01

    Heparin is the most widely used pharmaceutical to control blood coagulation in modern medicine. A health crisis that took place in 2008 led to a demand for production of heparin from non-animal sources. Chinese hamster ovary (CHO) cells, commonly used mammalian host cells for production of foreign pharmaceutical proteins in the biopharmaceutical industry, are capable of producing heparan sulfate (HS), a related polysaccharide naturally. Since heparin and HS share the same biosynthetic pathway...

  18. Effects of Supplementation of Various Medium Components on Chinese Hamster Ovary Cell Cultures Producing Recombinant Antibody

    OpenAIRE

    Kim, Do Yun; Lee, Joon Chul; Chang, Ho Nam; Oh, Duk Jae

    2005-01-01

    Thirteen vitamins, twenty amino acids, hormones, inorganic salts, and other chemical agents, which constitute typical serum-free media, were evaluated for the development of fortified medium to enhance cell growth and productivity of recombinant antibody in the cultures of the recombinant Chinese hamster ovary (rCHO) cells. Two different rCHO cell lines, rCHO-A producing recombinant antibodies against the human platelet and rCHO-B secreting recombinant antibodies against the S surface antigen...

  19. Binding and uptake of diphtheria toxin by toxin-resistant Chinese hamster ovary and mouse cells.

    OpenAIRE

    Didsbury, J R; Moehring, J M; Moehring, T. J.

    1983-01-01

    We investigated two phenotypically distinct types of diphtheria toxin-resistant mutants of Chinese hamster cells and compared their resistance with that of naturally resistant mouse cells. All are resistant due to a defect in the process of internalization and delivery of toxin to its target in the cytosol, elongation factor 2. By cell hybridization studies, analysis of cross-resistance, and determination of specific binding sites for 125I-labeled diphtheria toxin, we showed that these cell s...

  20. Recent progress with the DNA repair mutants of Chinese hamster ovary cells

    International Nuclear Information System (INIS)

    Repair deficient mutants of Chinese hamster ovary (CHO) cells are being used to identify human genes that correct the repair defects and to study mechanisms of DNA repair and mutagenesis. Five independent tertiary DNA transformants were obtained from the EM9 mutant. In these clones a human DNA sequence was identified that correlated with the resistance of the cells to CldUrd. After Eco RI digestion, Southern transfer, and hybridization of transformant DNAs with the BLUR-8 Alu family sequence, a common fragment of 25 to 30 kb was present. 37 refs., 4 figs., 3 tabs

  1. 5-Azacytidine Induces Transgene Silencing by DNA Methylation in Chinese Hamster Cells

    OpenAIRE

    Broday, Limor; Lee, Yong-Woo; Costa, Max

    1999-01-01

    The cytosine analog 5-azacytidine (5-AzaC) is a demethylating agent that is also known to induce mutagenesis in mammalian cells. In this study, the mutagenic potential of this drug was tested in the G10 and G12 transgenic Chinese hamster cell lines, which have a single bacterial gpt gene integrated into the genome at different sites, with its expression driven by a simian virus 40 (SV40) promoter. We show that the mutation frequencies following a 48-h exposure to different concentrations of 5...

  2. Recovery from DNA synthesis in V 79 chinese hamster cells irradiated with UV light

    International Nuclear Information System (INIS)

    Mammalian cells recover from DNA synthesis inhibition by UV light before most of the pyrimidine dimers have been removed from the genome. Most of the rodent cells show a deficient dimer excision repair compared with normal human fibroblasts. Despite this fact they recover efficiently from DNA synthesis inhibition after UV. In Chinese hamster V 79 cells was found that this recovery takes place in the absence of a significant excision repair, and it seems to be directly coupled to a recovery in the rate of movement of the replication fork. 120 refs, 31 figs. (author)

  3. Cell killing and mutation induction on Chinese hamster cells by photoradiations

    International Nuclear Information System (INIS)

    Applying radiation directly on cells, far-uv is more effective than black light, and black light is more effective than white light in inducing proliferative death and in inducing resistance to 6-thioguanine (6-TG), ouabain and diptheria toxin (DT). Gold light has no killing and mutagenic effects on CHO (Chinese hamster ovary) cells. Use of filters showed that a small percentage of shorter wavelengths in the far-uv region is responsible for most of the killing and mutagenic effects in the unfiltered broad spectra of black and white light

  4. Improved antibody production in Chinese hamster ovary cells by ATF4 overexpression

    OpenAIRE

    Haredy, Ahmad M.; Nishizawa, Akitoshi; Honda, Kohsuke; Ohya, Tomoshi; Ohtake, Hisao; Omasa, Takeshi

    2013-01-01

    To improve antibody production in Chinese hamster ovary (CHO) cells, the humanized antibody-producing CHO DP-12-SF cell line was transfected with the gene encoding activating transcription factor 4 (ATF4), a central factor in the unfolded protein response. Overexpression of ATF4 significantly enhanced the production of antibody in the CHO DP-12-SF cell line. The specific IgG production rate of in the ATF4-overexpressing CHO-ATF4-16 cells was approximately 2.4 times that of the parental host c...

  5. Cell killing and mutation induction on Chinese hamster cells by photoradiations

    Energy Technology Data Exchange (ETDEWEB)

    Lam, C.K.C.

    1982-11-01

    Applying radiation directly on cells, far-uv is more effective than black light, and black light is more effective than white light in inducing proliferative death and in inducing resistance to 6-thioguanine (6-TG), ouabain and diptheria toxin (DT). Gold light has no killing and mutagenic effects on CHO (Chinese hamster ovary) cells. Use of filters showed that a small percentage of shorter wavelengths in the far-uv region is responsible for most of the killing and mutagenic effects in the unfiltered broad spectra of black and white light.

  6. Calculation of response of Chinese hamster cells to ions based on track structure theory

    Institute of Scientific and Technical Information of China (English)

    LiuXiao-Wei; ZhangChun-Xiang

    1997-01-01

    Considering biological cells as single target two-hit detectors,an analytic formula to calculate the response of cells to ions is developed based on track structure theory.In the calculation,the splitting deposition energy between ion kill mode and γ kill mode is not used.The results of calculation are in agreement with the experimental data for response of Chinese hamster cells,whose response to γ rays can be described by the response function of single target two hit detector to ions.

  7. Subcellular distribution of Pu-239 in the liver of rat, mouse, Syrian and Chinese hamster

    International Nuclear Information System (INIS)

    The aim of our studies was to elucidate the biochemical mechanisms responsible for the differences in the biological half life of actinides in the liver of different mammalian species. Rats and mice were chosen as models for rapid elimination, and Syrian and Chinese hamsters as models for slow elimination. To distinguish between fixation in lysosomes and mitochondria, the lysosomes were isolated following injection of Triton WR1339 6 days after 239Pu administration. The animals were sacrificed 4 days later. In order to study the possible association with ferritin, 59Fe was also injected. Liver homogenates were subjected to differential and isopycnic centrifugation in a sucrose density gradient. The typical shift in the density of the lysosomal marker acid phosphatase from rho approximately 1.2 to rho approximately 1.1 following Triton WR1339 injection was observed in all species. It was possible therefore to separate lysosomes from other cell organelles, especially mitochondria. It was concluded that: 1) Mitochondria can virtually be excluded as binding sites in all four species; 2) Lysosomes are one important storage site in rats, mice and Syrian hamsters; 3) If 239Pu is bound to another cell constituent in addition to lysosomes in the hamster species (which is not yet proven) its density should be approximately 1.17. (H.K.)

  8. Onderzoek naar de inductie van chromosoomafwijkingen en "sister- chromatid exchanges" door acrylamide met Chinese hamster cellen in vitro

    NARCIS (Netherlands)

    Knaap; A.G.A.C.; Bergkamp; W.G.M.; Groot; M.G.

    1986-01-01

    Acrylamide bleek een clastogene werking te hebben in een test op chromosoomafwijkingen met Chinese hamster cellen in vitro vanaf 0,1 mg/ml (1,4 mmol/l), zowel in aan- als afwezigheid van een systeem voor metaboliosche activering (S9). Tevens induceerde acrylamide in deze cellen een significante

  9. Bystander deixis

    DEFF Research Database (Denmark)

    Rijkhoff, Jan

    1998-01-01

    Romani and several other languages across the globe. The second part is concerned with the contextual factors that must have a place in a discourse model that wants to be able to handle linguistic manifestations of bystander deixis. Due the fact that Romani has typically been used for in...... have borrowed extensively from the Romani lexicon. It will appear that bystander deixis is a universally attested phenomenon which is not restricted to situations in which speakers wish to communicate without being understood by others....

  10. Transformation of UV-hypersensitive Chinese hamster ovary cell mutants with UV-irradiated plasmids

    International Nuclear Information System (INIS)

    Transfection of UV-hypersensitive, DNA repair-deficient Chinese hamster ovary (CHO) cell lines and parental, repair-proficient CHO cells with UV-irradiated pHaprt-1 or pSV2gpt plasmids resulted in different responses by recipient cell lines to UV damage in transfected DNA. Unlike results reported for human cells, UV irradiation of transfecting DNA did not stimulate genetic transformation of CHO recipient cells. In repair-deficient CHO cells, proportionally fewer transformants were produced with increasing UV damage than in repair-proficient cells in transfections with UV-irradiated hamster adenine phosphoribosyltransferase (APRT) gene contained in plasmid pHaprt-1. Transfection of CHO cells with UV-irradiated pSV2gpt resulted in neither decline in transformation frequencies in repair-deficient cell lines relative to repair-proficient cells nor stimulation of genetic transformation by UV damage in the plasmid. Blot hybridization analysis of DNA samples isolated from transformed cells showed no dramatic changes in copy number or arrangement of transfected plasmid DNA with increasing UV dose. The authors conclude responses of recipient cells to UV-damaged transfecting plasmids depend on type of recipient cell and characteristics of the genetic sequence used for transfection. (author)

  11. Isolation of hypoxanthine phosphoribosyltransferase-defective mutants in Chinese hamster V79 cells by tritium suicide

    International Nuclear Information System (INIS)

    Tritium suicide was shown to be a highly efficient method for isolating mutants defective in hypoxanthine incorporation in the Chinese hamster lung of one kill cycle were used for the next kill cycle. The kill cycles involved incorporation of (3H) hypoxanthine for 5 or 10 min, followed by storage of 3H-labelled cells at -700C for 4-10 days. 12 clones that survived the 3rd kill cycle were tested for incorporation of (3H)hypoxanthine and all were found to be defective. At least 6 of the clones have defective hypoxanthine phosphoribosyltransferase (HPRT) activity. One mutant, H19, chosen for further characterization, had HPRT with a 13-fold elevation in apparent Ksub(m) for phosphoribosylpyrophosphate (PRPP). Thin-layer chromatography of cell extracts showed that this mutant was incapable of converting intracellular hypoxanthine to IMP or to other purine metabolites. In addition, H19 was resistant to 6-thioguanine. (orig.)

  12. Further characterization of chinese hamster mutagen sensitive mutants using calicheamycin and neocarcinostatin

    International Nuclear Information System (INIS)

    To further characterize mutagen sensitive Chinese hamster V79 mutant cell lines two new radiomimetic agents i.e. calicheamycin (CAL) and neocarcinostatin (NCS) were used. Whereas X-rays produces a variety of non-specific lesions in the DNA, mainly single strand breaks (SSB), CAL induces only double strand breaks (DSB) at sequence specific sites (TCCT). NCS, on the other hand, causes SSB and to a much lesser extent apurinic sites at AGC sequences in the DNA. The obtained results demonstrate in most of the mutants and expected parallelism between X-ray sensitivity and sensitivity to the antitumor antibiotics CAL and NCS. Furthermore, enhanced sensitivities for chromosomal aberrations are overall and not due to specific types of aberrations. At present an explanation for the recorded chromosomal hypo-sensitivity of V-H1 cells for NCS awaits further experimentation. (authors)

  13. Silver stained core-like structures in chinese hamster metaphase Chromosomes.

    Science.gov (United States)

    Kaiserman, M Z; Burkholder, G D

    1980-01-01

    Chinese hamster metaphase chromosomes, subjected to prolonged hypotonic pretreatment and subsequently stained with ammoniacal silver, contained a darkly-stained core-like structure in each chromatid, surrounded by a halo of dispersed chromatin which was pale yellow to brown in color. The core was variable in its appearance, ranging from a continuous linear configuration to a spiral structure or a discontinuous, particulate structure. Within the centromeric regions, the cores frequently appeared more intensely stained than elsewhere in the chromosome. The nucleolus organizers also stained darkly and appeared to be attached to the core-like structures. It remains to be determined whether the cores represent a real component of metaphase chromosome structure, or whether they are artifacts resulting from abnormal chromatin aggregation arising at the time of chromosome preparation. PMID:6165446

  14. A Study on Antitoxic Role of Vesicular Monoamine Transporter 2 in Transgenic Chinese Hamster Overy Cells

    Institute of Scientific and Technical Information of China (English)

    叶民; 丁新生; 董海蓉; 仇镇宁; 管晓虹

    2003-01-01

    Objective:To study the antitoxic role of vesicular monoamine transporter 2 (VMAT2) in transpgenic Chinese Hamster ovary(CHO) cell.Methods:With the technology of transgene from PC12 to CHO,MTT reduction assay was used to detect MPP+ toxic effect on wild type CHO(wtCHO) and transgenic CHO.Meanwhile,the role of reserpine was also observed in MPP+ toxic effects.Results:The sensitivity of transgenic CHO to MPP+ was much less than that of wtCHO with 0.5 mmol/L MPP+.Transgenic CHO had the same sensitivity as wtCHO if rotenone was given.WtCHO,by given reserpine alone,didn''''''''t change its sensitivity to MPP+.Conclusions:VMAT2 has protective effect on transgenic CHO by transporting MPP+ to vesicles.

  15. Genetic analysis of tumorigenesis: a conserved region in the human and Chinese hamster genomes contains genetically identified tumor-suppressor genes

    International Nuclear Information System (INIS)

    Regional chromosome homologies were found in a comparison of human 11p with Chinese hamster 3p. By use of probes that recognize six genes of human 11p (INS, CAT, HBBC, CALC, PTH, and HRAS), the corresponding genes were localized by in situ hybridization on Chinese hamster chromosome 3. INS and CAT were located close to the centromere on 3p, whereas HBBC, CALC, and PTH were at 3q3-4 and HRAS at 3q4. Extensive prior data from chromosome studies of tumorigenic and tumor-derived Chinese hamster cells have suggested the presence of a tumor-suppressor gene on 3p. Two tumor-suppressor genes have been described on human 11p, one linked to CAT and one to INS. The present study raises the possibility that the Chinese hamster suppressor may be closely linked to INS or CAT

  16. The subcellular distribution of 239Pu, 241Am and 59Fe in the liver of rat and Chinese hamster as dependent on time

    International Nuclear Information System (INIS)

    The subcellular distribution of monomeric 239Pu, 241Am and iron in rat and Chinese hamster liver has been investigated by sucrose-, metrizamide- and Percoll-density gradients. In rat liver, the transuranium elements become and remain bound to typical lysosomes primary storage organelle in Chinese hamster liver. However, their apparent density in sucrose decreases with time, which possible indicates transition into telolysomes. The transuranium nuclides show a subcellular distribution which is quite different from that of iron. (orig.)

  17. Host range restriction of vaccinia virus in Chinese hamster ovary cells: relationship to shutoff of protein synthesis

    International Nuclear Information System (INIS)

    Chinese hamster ovary cells were found to be nonpermissive for vaccinia virus. Although early virus-induced events occurred in these cells (RNA and polypeptide synthesis), subsequent events appeared to be prevented by a very rapid and nonselective shutoff of protein synthesis. Within less than 2 h after infection, both host and viral protein syntheses were arrested. At low multiplicities of infection, inhibition of RNA synthesis with cordycepin resulted in failure of the virus to block protein synthesis. Moreover, infection of the cells in the presence of cycloheximide prevented the immediate onset of shutoff after reversal of cycloheximide. Inactivation of virus particles by uv irradiation also impaired the capacity of the virus to inhibit protein synthesis. These results suggested that an early vaccinia virus-coded product was implicated in the shutoff of protein synthesis. Either the nonpermissive Chinese hamster ovary cells were more sensitive to this inhibition than permissive cells, or a regulatory control of the vaccinia shutoff function was defective

  18. Host range restriction of vaccinia virus in Chinese hamster ovary cells: relationship to shutoff of protein synthesis.

    Science.gov (United States)

    Drillien, R; Spehner, D; Kirn, A

    1978-12-01

    Chinese hamster ovary cells were found to be nonpermissive for vaccinia virus. Although early virus-induced events occurred in these cells (RNA and polypeptide synthesis), subsequent events appeared to be prevented by a very rapid and nonselective shutoff of protein synthesis. Within less than 2 h after infection, both host and viral protein syntheses were arrested. At low multiplicities of infection, inhibition of RNA synthesis with cordycepin resulted in failure of the virus to block protein synthesis. Moreover, infection of the cells in the presence of cycloheximide prevented the immediate onset of shutoff after reversal of cycloheximide. Inactivation of virus particles by UV irradiation also impaired the capacity of the virus to inhibit protein synthesis. These results suggested that an early vaccinia virus-coded product was implicated in the shutoff of protein synthesis. Either the nonpermissive Chinese hamster ovary cells were more sensitive to this inhibition than permissive cells, or a regulatory control of the vaccinia shutoff function was defective.

  19. Effects of turmeric and its active principle, curcumin, on bleomycin-induced chromosome aberrations in Chinese hamster ovary cells

    OpenAIRE

    Araújo Maria Cristina P.; Dias Francisca da Luz; Kronka Sergio N.; Takahashi Catarina S.

    1999-01-01

    Naturally occurring antioxidants have been extensively studied for their capacity to protect organisms and cells from oxidative damage. Many plant constituents including turmeric and curcumin appear to be potent antimutagens and antioxidants. The effects of turmeric and curcumin on chromosomal aberration frequencies induced by the radiomimetic agent bleomycin (BLM) were investigated in Chinese hamster ovary (CHO) cells. Three concentrations of each drug, turmeric (100, 250 and 500 mg/ml) and ...

  20. Muscarinic acetylcholine receptor down-regulation limits the extent of inhibition of cell cycle progression in Chinese hamster ovary cells.

    OpenAIRE

    Detjen, K.; Yang, J; Logsdon, C D

    1995-01-01

    Cellular desensitization is believed to be important for growth control but direct evidence is lacking. In the current study we compared effects of wild-type and down-regulation-resistant mutant m3 muscarinic receptors on Chinese hamster ovary (CHO-K1) cell desensitization, proliferation, and transformation. We found that down-regulation of m3 muscarinic acetylcholine receptors was the principal mechanism of desensitization of receptor-activated inositol phosphate phospholipid hydrolysis in t...

  1. Repair-deficient xeroderma pigmentosum cells made UV light resistant by fusion with X-ray-inactivated Chinese hamster cells.

    OpenAIRE

    Karentz, D; Cleaver, J.E.

    1986-01-01

    Xeroderma pigmentosum (XP) is an autosomal recessive human disease, characterized by an extreme sensitivity to sunlight, caused by the inability of cells to repair UV light-induced damage to DNA. Cell fusion was used to transfer fragments of Chinese hamster ovary (CHO) chromosomes into XP cells. The hybrid cells exhibited UV resistance and DNA repair characteristics comparable to those expressed by CHO cells, and their DNA had greater homology with CHO DNA than did the DNA from XP cells. Cont...

  2. Isolation and characterization of Chinese hamster ovary cell variants defective in adhesion to fibronectin-coated collagen

    OpenAIRE

    1980-01-01

    Variant clones of Chinese hamster ovary (CHO) cells were selected for reduced adhesion to serum-coated tissue culture plates. These clones also displayed reduced adhesion to substrata composed of collagen layers coated with bovine serum or with fibronectin (cold-insoluble globulin). Wild-type (WT) and adhesion variant (ADv) cells grew at comparable rates in suspension culture, but the adhesion variants could not be grown in monolayer culture because of their inability to attach to the substra...

  3. Transfection of normal human and Chinese hamster DNA corrects diepoxybutane-induced chromosomal hypersensitivity of Fanconi anemia fibroblasts

    International Nuclear Information System (INIS)

    Cultured cells from individuals affected with Fanconi anemia (FA) exhibit spontaneous chromosome breakage and hypersensitivity to the cell killing and clastogenic effects of the difunctional alkylating agent diepoxybutane (DEB). The authors report here the correction of both of these DEB-hypersensitivity phenotypes of FA cells achieved by cotransfection of normal placental of Chinese hamster lung cell DNA and the plasmid pSV2-neo-SVgpt. Transfectants were selected for clonogenic survival after treatment with DEB at a dose of 5 μgml. At this dose of DEB, the clonogenicity of normal fibroblasts was reduced to 50% and that of FA fibroblasts was reduced to zero. DEB-resistant (DEB/sup r/) colonies selected in this system exhibited a normal response to DEB-induced chromosome breakage and resistance to repeated DEB treatment. The neo and gpt sequences were detected by Southern blot analysis of DNA from one of four DEB/sup r/ colonies independently derived from transfection of human DNA and one of three DEB/sup r/ colonies independently derived from transfection of Chinese hamster DNA. The results demonstrate that DNA sequences that complement the two hallmark cellular phenotypes (cellular and chromosomal hypersensitivity to alkylating agents) of FA are present in human as well as Chinese hamster DNA. The cloning of these genes using transfection strategies can be expected to enable molecular characterization of FA

  4. Killing effect of Chinese hamster V79 cells exposed to accelerated carbon ions and RBE determination

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Survival curves of Chinese hamster V79 cells exposed to accclerated carbon ions with linear energy transfers of 125.5, 200 and 700 keV/μm were measured, respectively. Inactivation cross sections corresponding to the irradiation above were deduced from the V79 cell survival curves. They are 7.86±0.17, 10.44±1.11 and 32.32±3.58 μm2 in turn. With the surviving response of V79 cells to 60Co γ-rays as a reference value, relative biological effectiveness at 10%, 20%, 50% and 80% survival levels were given for the accelerated carbon ions. The results showed that carbon ions with LET of 125.5 keV/μm had a higher value of RBE at all the four survival levels than the carbon ions with other LETs. It was prompted that the maximum value of RBE for the V79 cell surviving as the biological endpoint emerged at the LET below 200 keV/μm for carbon ions.

  5. Overexpressed human metallothionein IIA gene protects Chinese hamster ovary cells from killing by alkylating agents

    Energy Technology Data Exchange (ETDEWEB)

    Kaina, B.; Lohrer, H.; Karin, M.; Herrlich, P. (Kernforschungszentrum Karlsruhe, Karlsruhe (Germany, F.R.))

    1990-04-01

    Experiments were designed to detect survival advantages that cells gain by overexpressing metallothionein (MT). Chinese hamster ovary K1-2 cells and an x-ray-sensitive derivative were transfected with a bovine papillomavirus (BPV)-linked construct carrying the human metallothionein IIA (hMT-IIA) gene. Transfectants survived 40-fold higher levels of cadmium chloride, harbored at least 30 copies of hMT-IIA, and contained 25- to 166-fold more MT than the parent cells. Even under conditions of reduced glutathione synthesis, the transfectants were not more resistant to the lethal effects of ionizing radiation and bleomycin than the parent cells. Thus free radicals generated by these agents cannot be scavenged efficiently by MT in vivo. The hMT-IIA transfectants, however, but not control transfectants harboring a BPV-MT promoter-neo construct, tolerated significantly higher doses of the alkylating agents N-methyl-N-nitrosourea and N-methyl-N'-nitro-N-nitrosoguanidine. Resistance and MT overexpression occurred irrespective of selection and cultivation in cadmium and zinc. There was no increase in resistance to methyl methanesulfonate and N-hydroxyethyl-N-chloroethylnitrosourea. MT did not affect the degree of overall DNA methylation after N-methyl-N-nitrosourea treatment nor the level of O6-methylguanine-DNA methyltransferase. The results suggest that MT participates as a cofactor or regulatory element in repair or tolerance of toxic alkylation lesions.

  6. Characterization of recombinant human erythropoietin produced in Chinese hamster ovary cells

    Energy Technology Data Exchange (ETDEWEB)

    Davis, J.M.; Arakawa, T.; Strickland, T.W.; Yphantis, D.A.

    1987-05-05

    Physicochemical properties of recombinant human erythropoietin were examined. This protein, produced in Chinese hamster ovary cells, showed a conformation apparently identical with the natural product isolated from human urine when examined by circular dichroism, UV absorbance, and fluorescence spectroscopy. Sedimentation equilibrium experiments showed the recombinant erythropoietin preparation to be essentially a single macromolecular component with a molecular weight of 30,400 and a carbohydrate content of 39%. The Stokes radius of recombinant erythropoietin was estimated to be 32 A from gel filtration, much larger than the 20-A radius calculated for a sphere of the observed molecular weight. This difference may be ascribed to the extensive glycosylation. The fluorescence and phosphorescence spectra showed that the luminescent tryptophan(s) is (are) solvent-exposed and can be quenched by I/sup -/ and acrylamide but not by Cs/sup +/. On acid titration, the recombinant erythropoietin showed a conformational transition with a midpoint of pH 4.1. This suggests that the net charges on the protein moiety rather than on the whole molecule play a role in protein structure stability.

  7. Rapid amplification system for recombinant protein production in Chinese Hamster Ovary (CHO) Cells.

    Science.gov (United States)

    Metta, M K; Kunaparaju, R K; Tantravahi, S

    2016-01-01

    Recombinant therapeutic proteins have changed the face of modern medicine in the present trend and they continue to provide innovative therapies for deadly diseases. This study describes the development of a novel stable expression system for rapid amplification of genes in Chinese Hamster Ovary (CHO) cells. The expression system consists of a host CHO cell line and an expression vector (pUB-PyOri-D-C) which encodes for Polyomavirus (Py) Origin of Replication (PyOri) for amplification of integrated genes in the presence of Py Large T Antigen (PyLT) and Dihydrofolate Reductase (DHFR) selectable marker gene for selection in the presence of Methotrexate (MTX). Use of both PyOri/PyLT and DHFR can reduce the number of rounds of selection and amplification required for isolation of high producing clones. The efficiency of pUB-PyOri-D-C was compared with that of pUB-D-C plasmid using Green fluorescent protein (GFP) and Erythropoietin (EPO) as reporter proteins. Our results showed that pUB-PyOri-D-C-EPO can help development of high expressing clone in one round of selection/amplification as compared to multiple rounds of selection/amplification with pUB-D-C-EPO plasmid. CHO-DG44/EPO clone generated using pUB-PyOri-D-C-EPO gave a productivity of 119 mg/L in shake flask. PMID:26950459

  8. Characterization of ultraviolet light-induced ouabain-resistant mutations in Chinese hamster cells

    International Nuclear Information System (INIS)

    Ouabain-resistant mutations in Chinese hamster cells have been quantitatively characterized. The mutation frequencies were found to be induced curvilinearly with treatments of increasing doses of ultraviolet light (UV). For the range of UV doses tested (5-20 J/m2), the observed mutation frequency, Y, as a function of UV dose X, follows a curvilinear function, Y=(-28+13.37X - 1.52X2+0.08 X3).10-6. The frequencies of UV-induced mutations were directly correlated with cell survival, indicating a similar causal relationship between cell killing and mutation induction. Under the same experimental conditions, X-rays induced 6-thioguanine-, but not ouabain-, resistant mutations, UV-induced ouabain-resistant (ouasup(r)) mutants exhibit a selection disadvantage. Their phenotypic expressions are modifiable by various agents. Wild type and 16 ouasup(r) mutants were compared with respect to their sensitivity to ouabain inhibition of 86Rb uptake by whole cells. All the ouasup(r) mutants assayed are less sensitive to the drug than are wild-type cells. In the absence of ouabain, the Na+-K+-ATPase activities can be significantly higher or lower than that of the wild-type cells. (Auth.)

  9. Genotoxic Effects of PAH Containing Sludge Extracts in Chinese Hamster Ovary Cell Cultures

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Objective Many studies have been conducted in order to evaluate the genotoxicity of chemicals and waste materials, which utilized in vivo test protocols. The use of animals for routine toxicity testing is now questioned by a growing segment of society[1]. Methods Keeping the above fact in mind, we have conducted in the present study the genotoxicity evaluation of oily sludge samples generated from a petroleum refinery and petrochemical industry and ETP sludge from petroleum refinery using DNA damage, chromosomal aberration, p53 protein induction and apoptosis in short term in vitro mammalian Chinese Hamster Ovary cell cultures. Results It is evident from the results that the oily sludge compounds derived from petroleum refinery and petrochemical industry could cause DNA damage, chromosomal aberration, p53 protein accumulation and apoptotic cell death on exposure to oily sludge extracts in the presence of metabolic activation system (S-9 mix), however, ETP sludge extract could not cause significant genotoxicity in comparison to oily sludge extract and negative control. Conclusion The effect may be attributed to polycyclic aromatic hydrocarbons present in the samples as evidenced from GC-MS.

  10. Interaction of hyperthermia and radiation on the induction of division delay in Chinese hamster ovary cells

    International Nuclear Information System (INIS)

    The mitotic selection procedure for cell cycle analysis was used in the investigation of the interaction of hyperthermia and ionizing radiation on the induction and duration of division delay in Chinese hamster ovary cells. Hyperthermia (immersion in a 45 degrees C water bath) produced a blockade of cell cycle progression with a transition point in late G2-early M, approximately at the X-ray transition point (35 min prior to selection). The duration of division delay for heated cells depended on the time of immersion: 24 minutes/minute at 45 degrees C. Radiation-induced division delay occurred at a rate of 45 minutes/gray of X-irradiation. When hyperthermic exposure and X-irradiation were combined with less than 1 minute between treatments, a division delay resulted that was approximately the sum of the delays produced by the individual treatments. As the interval between treatments was increased, the overall division delay also increased beyond that which could be accounted for solely by the postponement of the second treatment. These results indicate that hyperthermia and radiation induce division delay by different mechanisms

  11. Xbp1-based engineering of secretory capacity enhances the productivity of Chinese hamster ovary cells.

    Science.gov (United States)

    Tigges, Marcel; Fussenegger, Martin

    2006-05-01

    A variety of successful transcription and translation engineering strategies implemented during the past decade have driven the specific productivity of mammalian cells to an apparent limit. Restricted post-translation competence has since been considered the major bottleneck preventing mammalian cells from fully exploiting their physiologic production capacity in a biopharmaceutical manufacturing scenario. Through ectopic expression of the human transcription factor Xbp1 (X-box-binding-protein 1), evolved to manage plasma cell differentiation and coordinate the unfolded protein response, we have specifically expanded the endoplasmic reticulum and the Golgi of transgenic Chinese hamster ovary (CHO-K1)-derived cell lines with a resulting increase in overall production capacity. Xbp-1-based engineering of secretory bottlenecks was compatible with a variety of different promoter–product gene configurations suggesting that Xbp-1 induces generic production increases in CHO-K1 cell derivatives. Secretion engineering, illustrated here by Xbp1-based reprogramming of the post-translational processing machinery, provides a first insight into mastering a major system bottleneck which impacts biopharmaceutical manufacturing of secreted protein therapeutics.

  12. Killing effect of Chinese hamster V79 cells exposed to accelerated carbon ions and RBE determination

    Institute of Scientific and Technical Information of China (English)

    LIQiang; ZHOUGuang-Ming; 等

    2002-01-01

    Survival curves of Chinese hamster V79 cells exposed to accelerated carbon ions with linear energy transfers of 125.5,200 and 700keV/um were measured,respectively,Inactivation cross sections corresponding to the irradiation above were deduced from the V79 cell survival curves.They are 7.86±0.17,10.44±1.11 and 32.32±3.59um2 in turn.With the surviving response of V79 cells to 60Co γ-rays as a reference value,relative biological effectiveness at 10%,20%,50%and 80% survival levels were given for the accelerated carbon ions,The results showed that carbon ions with LET of 125.5keV/um had a higher value of RBE at all the four survival levels than the carbon ions with other LETs.It was prompted that the maximum value of RBE for the V79 cell surviving as the biological endpoint emerged at the LET below 200keV/um for carbon ions.

  13. 31P NMR analysis of membrane phospholipid organization in viable, reversibly electropermeabilized Chinese hamster ovary cells

    International Nuclear Information System (INIS)

    Chinese hamster ovary (CHO) cells were reversibly permeabilized by submitting them to short, high-intensity, square wave pulses (1.8 kV/cm, 100 μs). The cells remained in a permeable state without loss of viability for several hours at 40C. A new anisotropic peak with respect to control cells was observed on 31P NMR spectroscopic analysis of the phospholipid components. This peak is only present when the cells are permeable, and normal anisotropy is recovered after resealing. Taking into account the fusogenicity of electropermeabilized cells, comparative studies were performed on 5% poly(ethylene glycol) treated cells. The 31P NMR spectra of the phospholipids displayed the same anisotropic peak as in the case of the electropermeabilized cells. In the two cases, this anisotropic peak was located downfield from the main peak associated to the phospholipids when organized in bilayers. The localization of this anisotropic peak is very different from the one of a hexagonal phase. The authors proposed a reorganization of the polar head group region leading to a weakening of the hydration layer to account for these observations. This was also thought to explain the electric field induced fusogenicity of these cells

  14. Interactive cytotoxicity of etoposide and radiation on cultured Chinese hamster V-79 cells

    International Nuclear Information System (INIS)

    Etoposide is a semisynthetic derivative of podophyllotoxin and is an active antitumor agent. The interactive cytotoxic effect of Etoposide and radiation was investigated using cultured Chinese hamster V-79 cells. The surviving fraction of the cells was reduced by only 20%, when the cells were exposed to 5μg/ml of Etoposide for 30 min. Etoposide at this concentration reduced the width of the shoulder of the radiation survival curve. The change became more significant with increase in the concentration of Etoposide. The Dqs (quasithreshold doses) of the radiation survival curves were 5.39, 3.28, 2.13 and 0.54Gy, although the Dos (37% dose slopes) of the radiation survival curves were 2.55, 2.49, 2.39 and 2.18 Gy, when combination treatment with radiaiton and 0, 5, 10 and 20 μg/ml of Etoposide, respectively, was carried out. The cytotoxic effect became increased when fractional treatments with Etoposide and radiation were performed. The results obtained suggest that the mechanism of the interactive cytotoxic effect of this combination treatment involves a reciprocal action of Etoposide and sublethal damage by the radiation to the cells. (author)

  15. Interactive cytotoxicity of etoposide and radiation on cultured Chinese hamster V-79 cells

    Energy Technology Data Exchange (ETDEWEB)

    Saito, Tsutomu; Shimada, Yuji; Kamata, Rikisaburo (Nihon Univ., Tokyo (Japan). School of Medicine)

    1989-10-01

    Etoposide is a semisynthetic derivative of podophyllotoxin and is an active antitumor agent. The interactive cytotoxic effect of Etoposide and radiation was investigated using cultured Chinese hamster V-79 cells. The surviving fraction of the cells was reduced by only 20%, when the cells were exposed to 5mug/ml of Etoposide for 30 min. Etoposide at this concentration reduced the width of the shoulder of the radiation survival curve. The change became more significant with increase in the concentration of Etoposide. The Dqs (quasithreshold doses) of the radiation survival curves were 5.39, 3.28, 2.13 and 0.54Gy, although the Dos (37% dose slopes) of the radiation survival curves were 2.55, 2.49, 2.39 and 2.18 Gy, when combination treatment with radiaiton and 0, 5, 10 and 20 mug/ml of Etoposide, respectively, was carried out. The cytotoxic effect became increased when fractional treatments with Etoposide and radiation were performed. The results obtained suggest that the mechanism of the interactive cytotoxic effect of this combination treatment involves a reciprocal action of Etoposide and sublethal damage by the radiation to the cells. (author).

  16. A Chinese hamster ovary cell line hypersensitive to ionizing radiation and deficient in repair replication

    International Nuclear Information System (INIS)

    An X-ray-sensitive Chinese hamster ovary cell line was isolated by means of a semi-automated procedure in which mutagenized cells formed colonies on top of agar, were X-irradiated, and were photographed at two later times. The author compared the photographs to identify colonies that displayed significant growth arrest. One of the colonies identified in this manner produced a stable line (irs1SF) that is hypersensitive to ionizing radiation. irs1SF performs only half as much X-ray-induced repair replication as the parental line, indicating a defect in excision repair. This defect is believed to be the primary cause of the line's radiosensitivity. Although irs1SF repairs DNA double-strand breaks at a normal rate, it repairs single-strand breaks more slowly than normal. irs1SF has an elevated number of spontaneous chromatid aberrations and produces significantly higher numbers of X-ray-induced chromatid aberrations after exposure during the G1 phase of the cell cycle. The line is hypomutable, with X-ray exposure inducing only one-third as many 6-thioguanine-resistant colonies as the parental line. 45 refs.; 10 figs.; 1 table

  17. Resistance to DNA denaturation in irradiated Chinese hamster V79 fibroblasts is linked to cell shape

    International Nuclear Information System (INIS)

    Exponentially growing Chinese hamster V79-171b lung fibroblasts seeded at high density on plastic (approximately 7 x 10(3) cells/cm2) flatten, elongate, and produce significant amounts of extracellular fibronectin. When lysed in weak alkali/high salt, the rate of DNA denaturation following exposure to ionizing radiation is exponential. Conversely, cells plated at low density (approximately 7 x 10(2) cells/cm2) on plastic are more rounded 24 h later, produce little extracellular fibronectin, and display unusual DNA denaturation kinetics after X-irradiation. DNA in these cells resists denaturation, as though constraints to DNA unwinding have developed. Cell doubling time and distribution of cells in the growth cycle are identical for both high and low density cultures as is cell survival in response to radiation damage. The connection between DNA conformation and cell shape was examined further in low density cultures grown in conditioned medium. Under these conditions, cells at low density were able to elongate, and DNA denaturation of low density cultures was identical to that of high density cultures. Conversely, cytochalasin D, which interferes with actin polymerization causing cells to round up and release fibronectin, allowed development of constraints in high density cultures. These results suggest that DNA conformation is sensitive to changes in cell shape which result when cells are grown in different environments. However, these changes in DNA conformation detected by the DNA unwinding assay do not appear to play a direct role in radiation-induced cell killing

  18. Isolation and characterization of a Chinese hamster ovary cell mutant with altered regulation of phosphatidylserine biosynthesis

    International Nuclear Information System (INIS)

    We have screened approximately 10,000 colonies of Chinese hamster ovary (CHO) cells immobilized on polyester cloth for mutants defective in [14C]ethanolamine incorporation into trichloroacetic acid-precipitable phospholipids. In mutant 29, discovered in this way, the activities of enzymes involved in the CDP-ethanolamine pathway were normal; however, the intracellular pool of phosphorylethanolamine was elevated, being more than 10-fold that in the parental CHO-K1 cells. These results suggested that the reduced incorporation of [14C]ethanolamine into phosphatidylethanolamine in mutant 29 was due to dilution of phosphoryl-[14C]ethanolamine with the increased amount of cellular phosphorylethanolamine. Interestingly, the rate of incorporation of serine into phosphatidylserine and the content of phosphatidylserine in mutant 29 cells were increased 3-fold and 1.5-fold, respectively, compared with the parent cells. The overproduction of phosphorylethanolamine in mutant 29 cells was ascribed to the elevated level of phosphatidylserine biosynthesis, because ethanolamine is produced as a reaction product on the conversion of phosphatidylethanolamine to phosphatidylserine, which is catalyzed by phospholipid-serine base-exchange enzymes. Using both intact cells and the particulate fraction of a cell extract, phosphatidylserine biosynthesis in CHO-K1 cells was shown to be inhibited by phosphatidylserine itself, whereas that in mutant 29 cells was greatly resistant to the inhibition, compared with the parental cells. As a conclusion, it may be assumed that mutant 29 cells have a lesion in the regulation of phosphatidylserine biosynthesis by serine-exchange enzyme activity, which results in the overproduction of phosphatidylserine and phosphorylethanolamine as well

  19. Removal of radiation damage by subpopulations of plateau-phase Chinese hamster ovary cells

    International Nuclear Information System (INIS)

    Specific cellular radiobiology studies are often required to test aspects of the mathematical models developed in the Radiation Dosimetry program. These studies are designed to determine whether specific mathematical expressions, which characterize the expected effect of biochemical mechanisms on observable biological responses, are consistent with the behavior of selected cell lines. Since these tests place stringent requirements on the cellular system, special techniques and culture conditions are required to minimize biological variability. The use of specialized cell populations is providing data on the extent of repair following low doses, and on the changes in the types of damage that can be repaired as the cell progresses toward mitosis. The stationary-phase Chinese hamster ovary (CHO) cells are composed primarily of G(1)-phase cells (83%), with the remainder comprising both G(2) and S phases. Removal of radiation damage by cells was studied in split-dose experiments. To date, we have observed no significant differences in cellular repair rate. This suggests, therefore, that each of the repair processes found in stationary-phase cells is cell-age independent. However, cellular radiation sensitivity does change rapidly and considerably as the cells progress from one phase to the next through the cell cycle. Since the rate of damage removal appears invariant, the change in survival must reflect the efficiency of producing that damage. The experimental data suggest that production of one or another sort of damage probably dominates during specific phases of the cell cycle, while the capacity for removal of all types of damage remains relatively constant

  20. Metabolic analysis of antibody producing Chinese hamster ovary cell culture under different stresses conditions.

    Science.gov (United States)

    Badsha, Md Bahadur; Kurata, Hiroyuki; Onitsuka, Masayoshi; Oga, Takushi; Omasa, Takeshi

    2016-07-01

    Chinese hamster ovary (CHO) cells are commonly used as the host cell lines concerning their ability to produce therapeutic proteins with complex post-translational modifications. In this study, we have investigated the time course extra- and intracellular metabolome data of the CHO-K1 cell line, under a control and stress conditions. The addition of NaCl and trehalose greatly suppressed cell growth, where the maximum viable cell density of NaCl and trehalose cultures were 2.2-fold and 2.8-fold less than that of a control culture. Contrariwise, the antibody production of both the NaCl and trehalose cultures was sustained for a longer time to surpass that of the control culture. The NaCl and trehalose cultures showed relatively similar dynamics of cell growth, antibody production, and substrate/product concentrations, while they indicated different dynamics from the control culture. The principal component analysis of extra- and intracellular metabolome dynamics indicated that their dynamic behaviors were consistent with biological functions. The qualitative pattern matching classification and hierarchical clustering analyses for the intracellular metabolome identified the metabolite clusters whose dynamic behaviors depend on NaCl and trehalose. The volcano plot revealed several reporter metabolites whose dynamics greatly change between in the NaCl and trehalose cultures. The elastic net identified some critical, intracellular metabolites that are distinct between the NaCl and trehalose. While a relatively small number of intracellular metabolites related to the cell growth, glucose, glutamine, lactate and ammonium ion concentrations, the mechanism of antibody production was suggested to be very complicated or not to be explained by elastic net regression analysis. PMID:26803706

  1. Radiation Survival in Synchronous and Asynchronous Chinese Hamster Cells In Vitro

    International Nuclear Information System (INIS)

    Synchronized mammalian cells enable radiation responses to be examined as a function of the position of the cell within its generation cycle. However, synchrony techniques are limited by the random distribution of generation rates in cell populations and, because of the techniques employed, stages such as G2 and mitosis are difficult to examine. Superposing on the mitotic selection technique high-specific- activity tritiated thymidine to inactivate resistant S cells enables the average sensitivity of G2 and mitotic cells to be established. The changes in sensitivity during the cell cycle for Chinese hamster cells are considerable, at least as great as the effect of the presence or absence of oxygen. G2 and mitosis are the most sensitive cells, followed by G1, early S and finally late S cells as the most resistant. With this data the response of an asynchronous population can be estimated and compared with experimental data. Calculation and experiment agree well. The selection + tritiated thymidine technique is still limited in resolution to a one-hour period. Experiments varying the interval between irradiation and selection indicate that there is, very probably, a brief phase more sensitive than the average in the selected mitotic population which should be examined further. Experiments with Janus (fission) neutrons indicate that the changes in response during the cell cycle are smaller than for X-rays and the shapes of the survival curves are different. The RBE of these neutrons is shown to vary with both dose level and position in the cell cycle. (author)

  2. 5-Azacytidine Induces Transgene Silencing by DNA Methylation in Chinese Hamster Cells

    Science.gov (United States)

    Broday, Limor; Lee, Yong-Woo; Costa, Max

    1999-01-01

    The cytosine analog 5-azacytidine (5-AzaC) is a demethylating agent that is also known to induce mutagenesis in mammalian cells. In this study, the mutagenic potential of this drug was tested in the G10 and G12 transgenic Chinese hamster cell lines, which have a single bacterial gpt gene integrated into the genome at different sites, with its expression driven by a simian virus 40 (SV40) promoter. We show that the mutation frequencies following a 48-h exposure to different concentrations of 5-AzaC were 10 to 20 times higher than those of any of the other numerous mutagens that have been tested in the G10-G12 system. Moreover, the mutation frequencies were much higher in the G10 cell line than in the G12 cells. Detailed molecular analysis of the 6-thioguanine (6-TG)-resistant variants demonstrated that transgene silencing by de novo DNA methylation and increased chromatin condensation in the SV40 promoter was the major factor responsible for this high level of 6-TG resistance. As would be expected, exposure to 5-AzaC lowered the overall genomic DNA methylation levels, but it unexpectedly caused hypermethylation and increased chromatin condensation of the transgene in both the G10 and G12 cell lines. These results provide the first evidence that 5-AzaC may also induce transgene-specific DNA methylation, a phenomenon that can further be used for the elucidation of the mechanism that controls silencing of foreign DNA. PMID:10082586

  3. Heterologous expression of active human uridine diphosphate glucuronosyltransferase 1A3 in Chinese hamster lung cells

    Institute of Scientific and Technical Information of China (English)

    Ya-Kun Chen; Xin Li; Shu-Qing Chen; Su Zeng

    2005-01-01

    AIM: To obtain the active human recombinant uridine diphosphate glucuronosyltransferase 1A3 (UGT1A3) enzyme from Chinese hamster lung (CHL) cells.METHODS: The full-length UGT1A3 gene was amplified by reverse transcription-polymerase chain reaction (RT-PCR)using total RNA from human liver as template. The correct fragment confirmed by sequencing was subcloned into the mammalian expression vector pcDNA3.1 (+), and the recombinant vector was transfected into CHL cells using a calcium phosphate method. Expressed UGT1A3 protein was prepared from CHL cells resistant to neomycin (G418). Then the protein was added into a reaction mixture for glucuronidation of quercetin. The glucuronidation activity of UGT1A3 was determined by reverse phase-high performance liquid chromatography (RP-HPLC) coupled with a diode array detector (DAD). The quercetin glucuronide was confirmed by hydrolysis with β-glucuronidase. Control experiments were performed in parallel. The transcriptions of recombinants were also determined by RT-PCR.RESULTS: The gene was confirmed to be an allele (UGT1A3-3) of UGT1A3 by DNA sequencing. The fragment was introduced into pcDNA3.1 (+) successfully. Several colonies were obtained under the selection pressure of G418.The result of RT-PCR showed transcription of recombinants in mRNA level. Glucuronidation assay and HPLC analysis indicated UGT1A3 expressed heterologously in CHL cells was in an active form, and one of the gulcuronides corresponding to quercetin was also detected.CONCLUSION: Correct sequence of UGT1A3 gene can be obtained, and active UGT1A3 enzyme is expressed heterologously in CHL cells.

  4. Metabolic engineering of Chinese hamster ovary cells: towards a bioengineered heparin.

    Science.gov (United States)

    Baik, Jong Youn; Gasimli, Leyla; Yang, Bo; Datta, Payel; Zhang, Fuming; Glass, Charles A; Esko, Jeffrey D; Linhardt, Robert J; Sharfstein, Susan T

    2012-03-01

    Heparin is the most widely used pharmaceutical to control blood coagulation in modern medicine. A health crisis that took place in 2008 led to a demand for production of heparin from non-animal sources. Chinese hamster ovary (CHO) cells, commonly used mammalian host cells for production of foreign pharmaceutical proteins in the biopharmaceutical industry, are capable of producing heparan sulfate (HS), a related polysaccharide naturally. Since heparin and HS share the same biosynthetic pathway, we hypothesized that heparin could be produced in CHO cells by metabolic engineering. Based on the expression of endogenous enzymes in the HS/heparin pathways of CHO-S cells, human N-deacetylase/N-sulfotransferase (NDST2) and mouse heparan sulfate 3-O-sulfotransferase 1 (Hs3st1) genes were transfected sequentially into CHO host cells growing in suspension culture. Transfectants were screened using quantitative RT-PCR and Western blotting. Out of 120 clones expressing NDST2 and Hs3st1, 2 clones, Dual-3 and Dual-29, were selected for further analysis. An antithrombin III (ATIII) binding assay using flow cytometry, designed to recognize a key sugar structure characteristic of heparin, indicated that Hs3st1 transfection was capable of increasing ATIII binding. An anti-factor Xa assay, which affords a measure of anticoagulant activity, showed a significant increase in activity in the dual-expressing cell lines. Disaccharide analysis of the engineered HS showed a substantial increase in N-sulfo groups, but did not show a pattern consistent with pharmacological heparin, suggesting that further balancing the expression of transgenes with the expression levels of endogenous enzymes involved in HS/heparin biosynthesis might be necessary. PMID:22326251

  5. Bioactivation of mitomycin antibiotics by aerobic and hypoxic Chinese hamster ovary cells overexpressing DT-diaphorase.

    Science.gov (United States)

    Belcourt, M F; Hodnick, W F; Rockwell, S; Sartorelli, A C

    1996-06-28

    DT-Diaphorase catalyzes a two-electron reduction of mitomycin C (MC) and porfiromycin (POR) to reactive species. Many cell lines that overexpress DT-diaphorase and are sensitive to the mitomycins are protected from the aerobic cytotoxicity of these drugs by the DT-diaphorase inhibitor dicumarol. The cytoprotective properties of this relatively non-specific inhibitor, however, vanish under hypoxic conditions. To ascertain the role of DT-diaphorase in mitomycin bioactivation and cytotoxicity in living cells, a rat liver DT-diaphorase cDNA was transfected into Chinese hamster ovary cells. MC was equitoxic to the parental cells under oxygenated and hypoxic conditions. In contrast, POR was less toxic than MC to these cells under aerobic conditions, but significantly more toxic than MC under hypoxia. Two DT-diaphorase-transfected clones displayed increases in DT-diaphorase activity of 126- and 133-fold over parental cells. The activities of other oxidoreductases implicated in mitomycin bioreduction were unchanged. MC was more toxic to both DT-diaphorase-transfected lines than to parental cells; the toxicity of MC to the transfected lines was similar in air and hypoxia. POR was also more toxic to the DT-diaphorase-elevated clones than to parental cells under oxygenated conditions. Under hypoxia, however, the toxicity of POR to the transfected clones was unchanged from that of parental cells. The findings implicate DT-diaphorase in mitomycin bioactivation in living cells, but suggest that this enzyme does not contribute to the differential toxicity of MC or POR in air and hypoxia. PMID:8687482

  6. Isolation and characterization of a Chinese hamster ovary cell line deficient in fatty alcohol:NAD+ oxidoreductase activity.

    OpenAIRE

    James, P F; Rizzo, W B; Lee, J.; Zoeller, R A

    1990-01-01

    We have isolated a mutant Chinese hamster ovary cell line that is defective in long-chain fatty alcohol oxidation. The ability of the mutant cells to convert labeled hexadecanol to the corresponding fatty acid in vivo was reduced to 5% of the parent strain. Whole-cell homogenates from the mutant strain, FAA.1, were deficient in long-chain fatty alcohol:NAD+ oxidoreductase (FAO; EC 1.1.1.192) activity, which catalyzes the oxidation of hexadecanol to hexadecanoic acid, although the intermediate...

  7. [Experimental therapy in Chinese hamsters and rats infected with larval Echinococcus multilocularis by using mebendazole, albendazole and ivermectin with brief review of chemotherapy of human multilocular echinococcosis].

    Science.gov (United States)

    Inaoka, T; Nakao, M; Ohnishi, K; Kutsumi, H

    1987-01-01

    The effects of the mebendazole, albendazole and ivermectin on secondary multilocular echinococcosis in Chinese hamsters infected with intraperitoneal inoculation of protoscolices and in rats infected with transportal inoculation of protoscolices were investigated. A reduction in weight of the hydatids greater than 95% was recorded in Chinese hamsters intraperitoneally injected with mebendazole suspension. Oral administration of mebendazole moderately inhibited the development of the hydatids. Albendazole was less effective than mebendazole. Ivermectin was ineffective. The treatment with mebendazole of larval E. multilocularis inhibited the growth of the hydatids but it could not completely kill the parasite tissues. The present status of chemotherapy of the human multilocular echinococcosis was briefly discussed. PMID:3546045

  8. The subcellular distribution of 239Pu, 241Am and 59Fe in the liver of rat and Chinese hamster as dependent on time

    International Nuclear Information System (INIS)

    The subcellular distribution of monomeric 239Pu, 241Am and iron in rat and Chinese hamster liver has been investigated by sucrose-, metrizamide- and Percoll-density gradients. In rat liver, the transuranium elements become and remain bound to typical lysosomes up to several months after incorporation. Lysosomes are also the primary storage organelle in Chinese hamster liver. However, their apparent density in sucrose decreases with time, which possibly indicates transition into telolysomes. The transuranium nuclides show a subcellular distribution which is quite different from that of iron. (orig.)

  9. Conditionally lethal mutations in chinese hamster cells. Characterization of a cell line with a possible defect in the Krebs cycle.

    Science.gov (United States)

    DeFrancesco, L; Werntz, D; Scheffler, I E

    1975-04-01

    A variant Chinese hamster cell line has been isolated from a mutagenized population that has a markedly reduced ability to oxidize a variety of substrates via the Krebs cycle. The production of 14CO2 from 14C-labeled compounds was measured using pyruvate, acetate, beta-hydroxybutyrate, palmitate and glutamate, and in all cases it was neglibible in the mutant. In contrast to this, significant amounts of 14CO2 were produced from 14C-aspartate and 14C-succinate which suggest that some reactions of the Krebs cycle can take place and this conclusion is supported by tracer experiments with labeled compounds. The rate of respiration measured with a Clark oxygen electrode in the mutant was compared to several normal Chinese hamster cell lines and was found to be only 8%. Mitochondria appear to be present in normal numbers and with only minor differences in morphology. The measurement of difference spectra between oxidized and reduced states permits us to conclude that the cytochromes are all present and functional. These results lead us to believe that there may be a defect in the Krebs cycle between alpha-ketoglutarate and succinate. Alternatively a defect in a structural component of the mitochondria or in the electron-transport chain itself may be causing pleiotropic effects in the Krebs cycle and respiration.

  10. Understanding Transcriptional Enhancement in Monoclonal Antibody-Producing Chinese Hamster Ovary Cells

    Science.gov (United States)

    Nicoletti, Sarah E.

    With the demand for monoclonal antibody (mAB) therapeutics continually increasing, the need to better understand what makes a high productivity clone has gained substantial interest. Monoclonal antibody producing Chinese hamster ovary (CHO) cells with different productivities were provided by a biopharmaceutical company for investigation. Gene copy numbers, mRNA levels, and mAb productivities were previously determined for two low producing clones and their amplified progeny. These results showed an increase in mRNA copy number in amplified clones, which correlated to the observed increases in specific productivity of these clones. The presence of multiple copies of mRNA per one copy of DNA in the higher productivity clones has been coined as transcriptional enhancement. The methylation status of the CMV promoter as well as transcription factor/promoter interactions were evaluated to determine the cause of transcriptional enhancement. Methylation analysis via bisulfite sequencing revealed no significant difference in overall methylation status of the CMV promoter. These data did, however, reveal the possibility of differential interactions of transcription factors between the high and low productivity cell clones. This finding was further supported by chromatin immunoprecipitations previously performed in the lab, as well as literature studies. Transcription activator-like effector (TALE) binding proteins were constructed and utilized to selectively immunoprecipitate the CMV promoter along with its associated transcription factors in the different CHO cell clones. Cells were transfected with the TALE proteins, harvested and subjected to a ChIP-like procedure. Results obtained from the TALE ChIP demonstrated the lack of binding of the protein to the promoter and the need to redesign the TALE. Overall, results obtained from this study were unable to give a clear indication as to the causes of transcriptional enhancement in the amplified CHO cell clones. Further

  11. Coordinate amplification of metallothionein I and II genes in cadmium-resistant Chinese hamster cells: implications for mechanisms regulating metallothionein gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Crawford, B.D.; Enger, M.D.; Griffith, B.B.; Griffith, J.K.; Hanners, J.L.; Longmire, J.L.; Munk, A.C.; Stallings, R.L.; Tesmer, J.G.; Walters, R.A.; Hildebrand, C.E.

    1985-02-01

    The authors describe here the derivation, characterization, and use of clonal cadmium-resistance (Cd/sup r) strains of the Chinese hamster cell line CHO which differ in their metallothionein (MT) induction capacity. By nondenaturing polyacrylaminde gel electrophoresis, the authors showed that the stable Cd/sup r/ phenotype is correlated with the augmented expression of both isometallothioneins (MTI and MTII). In cells resistant to concentrations of CdCl2 exceeding 20 M, coordinate amplifications of genes encoding both isometallothioneins was demonstrated by using cDNA MT-coding sequence probes and probes specific for 3'-noncoding regions of Chinese hamster MTI and MTII genes. Molecular and in situ hybridization analyses supported close linkage of Chinese hamster MTI and MTII genes, which the authors have mapped previously to Chinese hamster chromosome 3. This suggests the existence of a functionally related MT gene cluster in this species. Amplified Cd/sup r/ variants expressing abundant MT and their corresponding Cd/sup s/ parental CHO cells should be useful for future studies directed toward elucidating the mechanisms that regulate expressions of the isometallothioneins. 59 references, 8 figures.

  12. Accelerated Homology-Directed Targeted Integration of Transgenes in Chinese Hamster Ovary Cells Via CRISPR/Cas9 and Fluorescent Enrichment

    DEFF Research Database (Denmark)

    Lee, Jae Seong; Grav, Lise Marie; Pedersen, Lasse Ebdrup;

    2016-01-01

    Targeted gene integration into site-specific loci can be achieved in Chinese hamster ovary (CHO) cells via CRISPR/Cas9 genome editing technology and the homology-directed repair (HDR) pathway. The low efficiency of HDR often requires antibiotic selection, which limits targeted integration...

  13. COMPARISON OF THE TOXICITY OF ACRYLAMIDE, CYCLOPHOSPHAMIDE, CHLRODECONE, AND DIETHYLSTILBESTROL IN CHINESE HAMSTER OVARY (CHO) CELLS WITH THEIR TOXICITY IN VIVO

    Science.gov (United States)

    In order to compare in vitro toxicity with in vivo toxicity, four chemicals that have been tested in the in vivo/in vitro toxicological screen proposed by the Health Effects Research Laboratory, EPA were tested in a Chinese Hamster Ovary (CHO) cytotoxicity assay. Viability index,...

  14. Influence of heterogenous alpha irradiation of Chinese hamster liver on survival and the induction of cancer. IV

    International Nuclear Information System (INIS)

    Estimation of risk to the human liver from deposited alpha-emitting radionuclides currently is based on epidemiological data accumulated from patients that received injections of the X-ray contrast medium Thorotrast. These exposures resulted in highly focal distributions of radiation dose, primarily around the liver sinusoids. It is, important to understand the applicability of these human data for extrapolating risk to people that are exposed to other liver-seeking alpha emitters, such as plutonium (Pu), where the distribution of alpha dose may be much more uniform and uncomplicated by the presence of large colloid masses in the liver tissue. In this study, Chinese hamsters received intravenous injections of Thorotrast (7.4, 1.5 or 0.30 Bq/g body weight) or monomeric 239Pu citrate (7.4 Bq/g), and were held for life-span observation. Using Cox proportional hazards analysis of the dose response for several neoplastic and hyperplastic lesions observed in the liver, it was found that the relative risk for each endpoint was increased in a dose related manner for all three dose levels of Thorotrast, and that the risks for the Pu-injected animals (7.4 Bq/g) were similar to those of the hamsters injected with 1.5 Bq/g Thorotrast. Dosimetry and pathological analyses are being continued to examine the dose-response relationships for these two patterns of alpha irradiation in greater detail, particularly as they affect the liver. (author)

  15. Influence of DMSO on Carbon K ultrasoft X-rays induced chromosome aberrations in V79 Chinese hamster cells

    International Nuclear Information System (INIS)

    Ultrasoft X-rays have been shown to be very efficient in inducing chromosomal aberrations in mammalian cells. The present study was aimed to evaluate the modifying effects of DMSO (a potent scavenger of free radicals) on the frequencies of chromosome aberrations induced by soft X-rays. Confluent held G1 Chinese hamster cells (V79) were irradiated with Carbon K ultrasoft X-rays in the presence and absence of 1 M DMSO and frequencies of chromosome aberrations in the first division cells were determined. DMSO reduced the frequencies of exchange types of aberrations (dicentrics and centric rings) by a factor of 2.1-3.5. The results indicate that free radicals induced by ultrasoft X-rays contribute to a great extent to the induction of chromosome aberrations. The possible implications of these results in interpreting the mechanisms involved in the high efficiency of ultrasoft X-rays in the induction of chromosome aberrations are discussed.

  16. Temperature dependence of anisotonic NaC1 effect on radiosensitization and ultrastructure of V79 Chinese hamster cells.

    Science.gov (United States)

    Szekely, J G; Raaphorst, G P; Lobreau, A U; Azzam, E I; Copps, T P

    1983-01-01

    Isodose radiation survival of V79 Chinese hamster cells, pretreated with strongly hypertonic concentrations of NaC1 at 22 degrees C, or at 37 degrees C, has been determined and correlated with ultrastructural changes within the nucleus. After an exposure of less than 10 min to 1.5 M NaC1, at both temperatures, the cells are radioprotected, but after longer exposures, the cells treated at 37 degrees C are radiosensitive, whereas those treated at 22 degrees C still show protection. The cells are radiosensitized at both temperatures by pretreatment with 0.5 M and 0.05 M NaC1. The ultrastructure of the nucleus observed after the anisotonic treatments suggests that contraction or swelling of chromatin may be associated with the observed variation in radiation sensitivity.

  17. Multi-omic profiling of EPO-producing Chinese hamster ovary cell panel reveals metabolic adaptation to heterologous protein production

    DEFF Research Database (Denmark)

    Ley, Daniel; Kazemi Seresht, Ali; Engmark, Mikael;

    2015-01-01

    Chinese hamster ovary (CHO) cells are the preferred production host for many therapeutic proteins. The production of heterologous proteins in CHO cells imposes a burden on the host cell metabolism and impact cellular physiology on a global scale. In this work, a multi-omics approach was applied...... the existence of production bottlenecks in energy metabolism (i.e., glycolytic metabolites, NAD(P)H/NAD(P)+ and ANPs) in batch culture or in the secretory protein production pathway (i.e., gene dosage, transcription and post-translational processing of EPO) in chemostat culture at specific productivities up...... to 5 pg/cell/day. Time-course analysis of high- and low-producing clones in chemostat culture revealed rapid adaptation of transcription levels of amino acid catabolic genes in favor of EPO production within nine generations. Interestingly, the adaptation was followed by an increase in specific EPO...

  18. The influence of non-uniform α-irradiation of Chinese hamster liver on chromosome damage and the induction of cancer

    International Nuclear Information System (INIS)

    In this study, Chinese hamsters received intravenous injections of Thorotrast (7.4, 1.5 or 0.30 Bq/g body weight) or monomeric 239Pu citrate (7.4 Bq/g), and were either sacrificed for cytogenetic analysis or held for lifespan dose-response observation. The frequency of chromosome aberrations observed in Thorotrast-exposed animals was 0.47 aberrations/cell Gy, similar to that in 239Pu citrate-injected hamsters. Using Cox proportional hazards analysis of the dose-response for several neoplastic and hyperplastic lesions observed in the liver, it was found that the relative risk for each endpoint was increased in a dose-related manner for all three dose levels of Thorotrast, and that risks for the plutonium-injected animals (7.4 Bq/g) were similar to those of hamsters injected with 1.5 Bq/g Thorotrast. (author)

  19. Cell growth stimulating effect of Ganoderma lucidum spores and their potential application for Chinese hamster ovary K1 cell cultivation.

    Science.gov (United States)

    Li, Ding; Zhong, Qi; Liu, Tingting; Wang, Jufang

    2016-06-01

    In this work, water-soluble extracts of Ganoderma lucidum spores (Gls), a Chinese medicinal herb that possesses cell growth stimulating function, were found to be an effective growth factor for Chinese hamster ovary (CHO) cell cultivation. The Gls extract was prepared and supplemented to CHO K1 cell culture media with various serum levels. Our results obtained from both the static culture and the spinner-flask suspension culture showed that use of small-amount Gls extract effectively promoted cell growth and suppressed cell apoptosis induced by serum deprivation with normal cell cycle maintained in a low-serum medium. The low-serum medium containing 1 % (v/v) fetal bovine serum (FBS) and 0.01 % (w/v) Gls extract showed a comparable performance on both cell growth and fusion protein productivity with the conventional CHO culture medium containing 10 % (v/v) FBS and a commercial serum-free medium. This is the first study of the potential of Gls extracts for use as an alternative cell growth factor and nutrient for CHO cells. The findings have presented a new approach to economic cultivation of CHO cells for therapeutic protein production.

  20. Cell growth stimulating effect of Ganoderma lucidum spores and their potential application for Chinese hamster ovary K1 cell cultivation.

    Science.gov (United States)

    Li, Ding; Zhong, Qi; Liu, Tingting; Wang, Jufang

    2016-06-01

    In this work, water-soluble extracts of Ganoderma lucidum spores (Gls), a Chinese medicinal herb that possesses cell growth stimulating function, were found to be an effective growth factor for Chinese hamster ovary (CHO) cell cultivation. The Gls extract was prepared and supplemented to CHO K1 cell culture media with various serum levels. Our results obtained from both the static culture and the spinner-flask suspension culture showed that use of small-amount Gls extract effectively promoted cell growth and suppressed cell apoptosis induced by serum deprivation with normal cell cycle maintained in a low-serum medium. The low-serum medium containing 1 % (v/v) fetal bovine serum (FBS) and 0.01 % (w/v) Gls extract showed a comparable performance on both cell growth and fusion protein productivity with the conventional CHO culture medium containing 10 % (v/v) FBS and a commercial serum-free medium. This is the first study of the potential of Gls extracts for use as an alternative cell growth factor and nutrient for CHO cells. The findings have presented a new approach to economic cultivation of CHO cells for therapeutic protein production. PMID:26921102

  1. In vitro neuroprotective action of recombinant rat erythropoietin produced by astrocyte cell lines and comparative studies with erythropoietin produced by Chinese hamster ovary cells

    OpenAIRE

    Masuda, Seiji; Kada, Emi; Nagao, Masaya; Sasaki, Ryuzo

    1999-01-01

    In the central nervous system, astrocytes produce erythropoietin (Epo) and neurons express its receptor. To examine whether or not the brain Epo protects the in vitro cultured neurons from glutamate-induced cell death, we established rat astrocyte cell lines containing the plasmid for production of recombinant rat Epo. Epo partially purified from the culture medium showed a neuroprotective effect similar to that of rat Epo produced by Chinese hamster ovary (CHO) cells. Comparison was made in ...

  2. Protective effect of enzymatic hydrolysates from highbush blueberry (Vaccinium corymbosum L.) against hydrogen peroxide-induced oxidative damage in Chinese hamster lung fibroblast cell line

    OpenAIRE

    Senevirathne, Mahinda; Kim, Soo-Hyun; Jeon, You-Jin

    2010-01-01

    Blueberry was enzymatically hydrolyzed using selected commercial food grade carbohydrases (AMG, Celluclast, Termamyl, Ultraflo and Viscozyme) and proteases (Alcalase, Flavourzyme, Kojizyme, Neutrase and Protamex) to obtain water soluble compounds, and their protective effect was investigated against H2O2-induced damage in Chinese hamster lung fibroblast cell line (V79-4) via various published methods. Both AMG and Alcalase hydrolysates showed higher total phenolic content as well as higher ce...

  3. The effect of dexamethasone on the radiation survival response and misonidazole-induced hypoxic-cell cytotoxicity in Chinese hamster cells V-79-753B in vitro

    International Nuclear Information System (INIS)

    Overnight exposure of Chinese hamster cells, V-79-753B, to microgram quantities of the synthetic corticosteroid, dexamethasone, resulted in a decrease in sensitivity towards radiation, both in air and in hypoxia. The effect was dose-modifying and the oxygen enhancement ratio did not change appreciably. Similarly, when dexamethasone-treated hypoxic cells were irradiated in the presence of misonidazole, a hypoxic cell radiosensitizer, there was a decrease in radiation sensitivity compared with untreated hypoxic cells irradiated with misonidazole. (author)

  4. Effect of Wortmannin on the repair profiles of DNA double-strand breaks in the whole genome and in interstitial telomeric sequences of Chinese hamster cells

    International Nuclear Information System (INIS)

    The DNA breakage detection-fluorescence in situ hybridization (DBD-FISH) procedure was applied to analyze the effect of Wortmannin (WM) in the rejoining kinetics of ionizing radiation-induced DNA double-strand breaks (DSBs) in the whole genome and in the long interstitial telomeric repeat sequence (ITRS) blocks from Chinese hamster cell lines. The results indicate that the ITRS blocks from wild-type Chinese hamster cell lines, CHO9 and V79B, exhibit a slower initial rejoining rate of ionizing radiation-induced DSBs than the genome overall. Neither Rad51C nor the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) activities, involved in homologous recombination (HR) and in non-homologous end-joining (NHEJ) pathways of DSB repair respectively, influenced the rejoining kinetics within ITRS in contrast to DNA sequences in the whole genome. Nevertheless, DSB removal rate within ITRS was decreased in the absence of Ku86 activity, though at a lower affectation level than in the whole genome, thus homogenizing both rejoining kinetics rates. WM treatment slowed down the DSB rejoining kinetics rate in ITRS, this effect being more pronounced in the whole genome, resulting in a similar pattern to that of the Ku86 deficient cells. In fact, no WM effect was detected in the Ku86 deficient Chinese hamster cells, so probably WM does not add further impairment in DSB rejoining than that resulted as a consequence of absence of Ku activity. The same slowing effect was also observed after treatment of Rad51C and DNA-PKcs defective hamster cells by WM, suggesting that: (1) there is no potentiation of the HR when the NHEJ is impaired by WM, either in the whole genome or in the ITRS, and (2) that this impairment may probably involve more targets than DNA-PKcs. These results suggest that there is an intragenomic heterogeneity in DSB repair, as well as in the effect of WM on this process

  5. Repair-deficient xeroderma pigmentosum cells made UV light resistant by fusion with X-ray-inactivated Chinese hamster cells

    International Nuclear Information System (INIS)

    Xeroderma pigmentosum (XP) is an autosomal recessive human disease, characterized by an extreme sensitivity to sunlight, caused by the inability of cells to repair UV light-induced damage to DNA. Cell fusion was used to transfer fragments of Chinese hamster ovary (CHO) chromosomes into XP cells. The hybrid cells exhibited UV resistance and DNA repair characteristics comparable to those expressed by CHO cells, and their DNA had greater homology with CHO DNA than did the DNA from XP cells. Control experiments consisted of fusion of irradiated and unirradiated XP cells and repeated exposure of unfused XP cells to UV doses used for hybrid selection. These treatments did not result in an increase in UV resistance, repair capability, or homology with CHO DNA. The hybrid cell lines do not, therefore, appear to be XP revertants. The establishment of these stable hybrid cell lines is an initial step toward identifying and cloning CHO DNA repair genes that complement the XP defect in human cells. The method should also be applicable to cloning genes for other diseases, such as ataxia-telangiectasia and Fanconi's anemia

  6. Characteristic element of matrix attachment region mediates vector attachment and enhances nerve growth factor expression in Chinese hamster ovary cells.

    Science.gov (United States)

    Wang, X Y; Zhang, J H; Sun, Q L; Yao, Z Y; Deng, B G; Guo, W Y; Wang, L; Dong, W H; Wang, F; Zhao, C P; Wang, T Y

    2015-01-01

    Preliminary studies have suggested that a characteristic element of the matrix attachment region (MAR) in human interferon-β mediates the adhesion of vectors to Chinese hamster ovary (CHO) cells. In this study, we investigated if vector adhesion increased nerve growth factor (NGF) expression in CHO cells. The MAR characteristic element sequence of human interferon-β was inserted into the multiple-cloning site of the pEGFP-C1 vector. The target NGF gene was inserted upstream of the MAR characteristic element sequence to construct the MAR/NGF expression vector. The recombinant plasmid was transfected into CHO cells and stable monoclonal cells were selected using G418. NGF mRNA and protein expression was detected by reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. Plasmid reduction experiments were used to determine the state of transfected plasmid in mammalian cells. The insertion of MAR into the vector increased NGF expression levels in CHO cells (1.93- fold) compared to the control. The recombinant plasmid expressing the MAR sequence was digested into a linear space vector. The inserted MAR and NGF sequences were consistent with those inserted into the plasmid before recombination. Therefore, we concluded that the MAR characteristic element mediates vector adhesion to CHO cells and enhances the stability and efficiency of the target gene expression. PMID:26345852

  7. Quantitative feature extraction from the Chinese hamster ovary bioprocess bibliome using a novel meta-analysis workflow.

    Science.gov (United States)

    Golabgir, Aydin; Gutierrez, Jahir M; Hefzi, Hooman; Li, Shangzhong; Palsson, Bernhard O; Herwig, Christoph; Lewis, Nathan E

    2016-01-01

    The scientific literature concerning Chinese hamster ovary (CHO) cells grows annually due to the importance of CHO cells in industrial bioprocessing of therapeutics. In an effort to start to catalogue the breadth of CHO phenotypes, or phenome, we present the CHO bibliome. This bibliographic compilation covers all published CHO cell studies from 1995 to 2015, and each study is classified by the types of phenotypic and bioprocess data contained therein. Using data from selected studies, we also present a quantitative meta-analysis of bioprocess characteristics across diverse culture conditions, yielding novel insights and addressing the validity of long held assumptions. Specifically, we show that bioprocess titers can be predicted using indicator variables derived from viable cell density, viability, and culture duration. We further identified a positive correlation between the cumulative viable cell density (VCD) and final titer, irrespective of cell line, media, and other bioprocess parameters. In addition, growth rate was negatively correlated with performance attributes, such as VCD and titer. In summary, despite assumptions that technical diversity among studies and opaque publication practices can limit research re-use in this field, we show that the statistical analysis of diverse legacy bioprocess data can provide insight into bioprocessing capabilities of CHO cell lines used in industry. The CHO bibliome can be accessed at http://lewislab.ucsd.edu/cho-bibliome/. PMID:26948029

  8. Increased recombinant protein production owing to expanded opportunities for vector integration in high chromosome number Chinese hamster ovary cells.

    Science.gov (United States)

    Yamano, Noriko; Takahashi, Mai; Ali Haghparast, Seyed Mohammad; Onitsuka, Masayoshi; Kumamoto, Toshitaka; Frank, Jana; Omasa, Takeshi

    2016-08-01

    Chromosomal instability is a characteristic of Chinese hamster ovary (CHO) cells. Cultures of these cells gradually develop heterogeneity even if established from a single cell clone. We isolated cells containing different numbers of chromosomes from a CHO-DG44-based human granulocyte-macrophage colony stimulating factor (hGM-CSF)-producing cell line and found that high chromosome number cells showed higher hGM-CSF productivity. Therefore, we focused on the relationship between chromosome aneuploidy of CHO cells and high recombinant protein-producing cell lines. Distribution and stability of chromosomes were examined in CHO-DG44 cells, and two cell lines expressing different numbers of chromosomes were isolated from the original CHO-DG44 cell line to investigate the effect of aneuploid cells on recombinant protein production. Both cell lines were stably transfected with a vector that expresses immunoglobulin G3 (IgG3), and specific antibody production rates were compared. Cells containing more than 30 chromosomes had higher specific antibody production rates than those with normal chromosome number. Single cell analysis of enhanced green fluorescent protein (Egfp)-gene transfected cells revealed that increased GFP expression was relative to the number of gene integration sites rather than the difference in chromosome numbers or vector locations. Our results suggest that CHO cells with high numbers of chromosomes contain more sites for vector integration, a characteristic that could be advantageous in biopharmaceutical production.

  9. Sensitization by wortmannin of heat- or X-ray induced cell death in cultured Chinese hamster V79 cells

    International Nuclear Information System (INIS)

    Here we found that wortmannin sensitized Chinese hamster V79 cells to hyperthermic treatment at 44.0 deg C as determined either by colony formation assay or by dye exclusion assay. Wortmannin enhanced heat-induced cell death accompanying cleavage of poly (ADP-ribose) polymerases (PARP). Additionally, the induction of heat shock protein HSP70 was suppressed and delayed in wortmannin-treated cells. Heat sensitizing effect of wortmannin was obvious at more than 5 or 10 μM of final concentrations, while radiosensitization was apparent at 5 μM. Requirement for high concentration of wortmannin, i.e., order of μM, suggests a possible role of certain protein kinases, such as DNA-PK and/or ATM among PI3-kinase family. The sensitization was minimal when wortmannin was added at the end of heat treatment. This was similar to the case of X-ray. Since heat-induced cell death and PARP cleavage preceded HSP70 induction phenomenon, the sensitization to the hyperthermic treatment was considered mainly caused by enhanced apoptotic cell death rather than secondary to suppression or delay by wortmannin of HSP70 induction. Further, in the present system radiosensitization by wortmannin was also at least partly mediated through enhancement of apoptotic cell death. (author)

  10. ¹H NMR spectroscopy profiling of metabolic reprogramming of Chinese hamster ovary cells upon a temperature shift during culture.

    Directory of Open Access Journals (Sweden)

    Jane L Wagstaff

    Full Text Available We report an NMR based approach to determine the metabolic reprogramming of Chinese hamster ovary cells upon a temperature shift during culture by investigating the extracellular cell culture media and intracellular metabolome of CHOK1 and CHO-S cells during culture and in response to cold-shock and subsequent recovery from hypothermic culturing. A total of 24 components were identified for CHOK1 and 29 components identified for CHO-S cell systems including the observation that CHO-S media contains 5.6 times the level of glucose of CHOK1 media at time zero. We confirm that an NMR metabolic approach provides quantitative analysis of components such as glucose and alanine with both cell lines responding in a similar manner and comparable to previously reported data. However, analysis of lactate confirms a differentiation between CHOK1 and CHO-S and that reprogramming of metabolism in response to temperature was cell line specific. The significance of our results is presented using principal component analysis (PCA that confirms changes in metabolite profile in response to temperature and recovery. Ultimately, our approach demonstrates the capability of NMR providing real-time analysis to detect reprogramming of metabolism upon cellular perception of cold-shock/sub-physiological temperatures. This has the potential to allow manipulation of metabolites in culture supernatant to improve growth or productivity.

  11. Dose dependence of the oxygen enhancement ratio (OER) in radiation inactivation of Chinese hamster V79-171 cells

    International Nuclear Information System (INIS)

    The dose dependence of the oxygen enhancement ratio (OER) has been examined through multiple measurements of the response of Chinese hamster V79-171 cells to low and high doses of radiation under aerobic and hypoxic conditions. In this series of experiments the cells were maintained at 37 degrees C throughout the gassing and irradiation periods, to simulate normal physiological conditions. Flow cytometry and cell sorting techniques were used to facilitate accurate measurement of cell survival throughout the dose range, but particularly at low dose. The OER was found to decrease significantly at low dose, qualitatively confirming earlier reports from this laboratory, though the decrease was somewhat smaller in the present series. This difference may be a temperature effect since in the earlier experiments irradiation was at 0 degree C. This report shows that the OER decreases from a value of 2.87 ± 0.16 (standard deviation of mean) at S = 0.01 to 2.36 ± 0.19 at S = 0.80. Both alpha and beta are altered by the presence of oxygen. The OER is presented as a function of dose in nitrogen

  12. Template free synthesis of silver-gold alloy nanoparticles and cellular uptake of gold nanoparticles in Chinese Hamster Ovary cell

    Energy Technology Data Exchange (ETDEWEB)

    Pal, Angshuman; Shah, Sunil [Department of Chemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara, Gujarat-390002 (India); Kulkarni, Vijay; Murthy, R.S.R. [G. H. Patel Pharmacy Building, TIFAC-CORE in NDDS, The Maharaja Sayajirao University of Baroda, Vadodara, Gujarat-390002 (India); Devi, Surekha [Department of Chemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara, Gujarat-390002 (India)], E-mail: surekha_devi@yahoo.com

    2009-01-15

    Gold-silver alloy nanoparticles were synthesized by simultaneous reduction of varying mole fractions of HAuCl{sub 4} and AgNO{sub 3} by sodium citrate in aqueous solution without using stabilizing agents such as surfactant or polymer. Appearance of single absorption peak in visible spectrum indicated formation of homogeneous gold-silver alloy nanoparticles. Transmission electron micrographs also support formation of alloy nanoparticles rather than core-shell particles. The plasmon absorption bands for Au-Ag nanoparticles show linear bathochromic shift with increasing Au content. No significant change in surface plasmon band was observed on storage of samples at 25 {+-} 2 deg. C for 6 months, indicating stability of the particles. Particle size distribution, zeta-potential and conduction of these colloidal suspensions were measured by dynamic light scattering along with Zetasizer. Gold and Au-Ag alloy nanoparticles exhibited fluorescence at 600 nm and in between 600 and 486 nm respectively depending on alloy composition. Gold nanoparticles were used for cell line study using liposome as a carrier. This liposome entrapped gold nanoparticles showed enhanced uptake by Chinese Hamster Ovary (CHO) cells compared to gold nanoparticles.

  13. Inhibition of DNA excision repair by methotrexate in Chinese hamster ovary cells following exposure to ultraviolet irradiation or ethylmethanesulfonate

    International Nuclear Information System (INIS)

    Previous results have suggested that methotrexate (MTX) could interfere with the repair of spontaneous DNA damage. To determine its effects on induced DNA damage, MTX was compared to hydroxyurea and arabinofuranosylcytosine (H/A), a drug combination known to block the DNA polymerase step of excision repair, for its ability to cause the accumulation of single-strand breaks (SSB) following exposure to either UV light or the alkylating agent ethylmethanesulfonate in Chinese hamster ovary cells. SSB were measured by alkaline elution 1, 2, and 6 h after exposure to either 1.8 mg/ml of ethylmethanesulfonate or 10 J/m2 of UV in cells pretreated with MTX or H/A. Following exposure to ethylmethanesulfonate, significant accumulation of SSB occurred in cells pretreated with either H/A or MTX. Coadministration of hypoxanthine and thymidine in MTX-treated cells prevented SSB accumulation, indicating that nucleotide depletion by MTX had inhibited repair synthesis. After UV irradiation, SSB accumulation was much less in MTX- than in H/A-treated cells. MTX was found to have no effect on the incision of UV damage. These results indicate that nucleotide depletion by MTX can affect the repair of DNA damage by exogenous agents, and that the extent of inhibition is dependent on the type of damage induced

  14. TOXICOLOGY STUDIES OF LEWISITE AND SULFUR MUSTARD AGENTS:GENETIC TOXICITY OF LEWISITE (L) IN CHINESE HAMSTER OVARY CELLS

    Energy Technology Data Exchange (ETDEWEB)

    Jostes,R.F. Jr.; Sasser, LB; Rausch, R.J.

    1989-05-31

    The cytotoxic clastogenic and mutagenic effects of the arsenic containing vesicant, Lewisite (L) [dichloro(2-chlorovinyl) arsine], have been investigated using Chinese hamster ovary cells. One hour exposures to Lewisite were cytotoxic in uM amounts. The cell survival response yields a D37 of 0.6 uM and an extrapolation number of 2.5. The mutagenic response at the hypoxantnine-guanine phosporibosyl transferase (HGPRT) locus was sporadic and not significantly greater than control values when cells were exposed over a range of 0.125 to2.0 uM. Sister chromatid exchange (SCE) induction, a measure of chromosomal rearrangement, was weakly positive over a range of 0.25 to 1.0 uM but the values were not significantly greater than the control response. Chromosomal aberrations were induced at 0.75 and 1.0 UMin one experiment and 0.5 and 0.75 uM in another experiment. The Induced values were significantly greater than the control values. Lewisite appears to be cytotoxic and clastogenic in our investigations but SCE and mutation at the HGPRT locus are not significantly greater than control values. Lewisita toxicity was in some ways similar to radiomimetic chemicals such as bleomycin.

  15. Chinese hamster ovary cell performance enhanced by a rational divide-and-conquer strategy for chemically defined medium development.

    Science.gov (United States)

    Liu, Yaya; Zhang, Weiyan; Deng, Xiancun; Poon, Hong Fai; Liu, Xuping; Tan, Wen-Song; Zhou, Yan; Fan, Li

    2015-12-01

    Basal medium design is considered one of the most important steps in process development. To optimize chemically defined (CD) media efficiently and effectively for the biopharmaceutical industry, a two-step rational strategy was applied to optimize four antibody producing Chinese hamster ovary (CHO) cell lines. In the first step, 48 of 52 components of our in-house medium were divided into three groups according to their characteristics. In the next step, these groups were optimized by spent medium analysis, response surface methodology and mixture design. Because these steps in our strategy involved dividing medium components into groups and subsequently adjusting the concentration of the components, we termed this medium development strategy "divide and conquer". By applying the strategy, we were able to improve the titers of CHO-S, CHO-DG44 and two CHO-K1 cell lines 1.92, 1.86, 2.92 and 1.62-fold, respectively, in 8 weeks with fewer than 60 tests. This divide-and-conquer strategy was efficient, effective, scalable and universal in our current study and offered a new approach to CD media development.

  16. Heterologous transmembrane signaling by a human insulin receptor-v-ros hybrid in Chinese hamster ovary cells

    Energy Technology Data Exchange (ETDEWEB)

    Ellis, L.; Morgan, D.O.; Jong, S.M.; Wang, L.H.; Roth, R.A.; Rutter, W.J.

    1987-08-01

    A hybrid receptor molecule composed of the extracellular ligand-binding domain of the human insulin receptor and the transmembrane and cytoplasmic (protein-tyrosine kinase) domains of the chicken sarcoma virus UR2 transforming protein p68/sup gag-ros/ has been constructed and expressed in Chinese hamster ovary (CHO) cells. The hybrid is processed normally into ..cap alpha.. and hybrid ..beta.. subunits, is expressed on the cell surface at high levels, and binds insulin with near-wild-type affinity. Furthermore, insulin stimulates the phosphorylation on tyrosine resides of the hybrid ..beta..-subunit in vivo and the phosphorylation of an exogeneous substrate (poly(Glu,Tyr)) in vitro. Thus the hybrid is capable of heterologous transmembrane signaling. However, the hybrid mediates neither the insulin-activated uptake of 2-deoxyglucose nor the incorporation of (/sup 3/H)thymidine into DNA, suggesting that the physiological response(s) mediated by ligand-activated protein-tyrosine kinases may utilize distinct intracellular mechanisms for postreceptor signaling

  17. Heterologous transmembrane signaling by a human insulin receptor-v-ros hybrid in Chinese hamster ovary cells

    International Nuclear Information System (INIS)

    A hybrid receptor molecule composed of the extracellular ligand-binding domain of the human insulin receptor and the transmembrane and cytoplasmic (protein-tyrosine kinase) domains of the chicken sarcoma virus UR2 transforming protein p68/sup gag-ros/ has been constructed and expressed in Chinese hamster ovary (CHO) cells. The hybrid is processed normally into α and hybrid β subunits, is expressed on the cell surface at high levels, and binds insulin with near-wild-type affinity. Furthermore, insulin stimulates the phosphorylation on tyrosine resides of the hybrid β-subunit in vivo and the phosphorylation of an exogeneous substrate [poly(Glu,Tyr)] in vitro. Thus the hybrid is capable of heterologous transmembrane signaling. However, the hybrid mediates neither the insulin-activated uptake of 2-deoxyglucose nor the incorporation of [3H]thymidine into DNA, suggesting that the physiological response(s) mediated by ligand-activated protein-tyrosine kinases may utilize distinct intracellular mechanisms for postreceptor signaling

  18. Increased recombinant protein production owing to expanded opportunities for vector integration in high chromosome number Chinese hamster ovary cells.

    Science.gov (United States)

    Yamano, Noriko; Takahashi, Mai; Ali Haghparast, Seyed Mohammad; Onitsuka, Masayoshi; Kumamoto, Toshitaka; Frank, Jana; Omasa, Takeshi

    2016-08-01

    Chromosomal instability is a characteristic of Chinese hamster ovary (CHO) cells. Cultures of these cells gradually develop heterogeneity even if established from a single cell clone. We isolated cells containing different numbers of chromosomes from a CHO-DG44-based human granulocyte-macrophage colony stimulating factor (hGM-CSF)-producing cell line and found that high chromosome number cells showed higher hGM-CSF productivity. Therefore, we focused on the relationship between chromosome aneuploidy of CHO cells and high recombinant protein-producing cell lines. Distribution and stability of chromosomes were examined in CHO-DG44 cells, and two cell lines expressing different numbers of chromosomes were isolated from the original CHO-DG44 cell line to investigate the effect of aneuploid cells on recombinant protein production. Both cell lines were stably transfected with a vector that expresses immunoglobulin G3 (IgG3), and specific antibody production rates were compared. Cells containing more than 30 chromosomes had higher specific antibody production rates than those with normal chromosome number. Single cell analysis of enhanced green fluorescent protein (Egfp)-gene transfected cells revealed that increased GFP expression was relative to the number of gene integration sites rather than the difference in chromosome numbers or vector locations. Our results suggest that CHO cells with high numbers of chromosomes contain more sites for vector integration, a characteristic that could be advantageous in biopharmaceutical production. PMID:26850366

  19. Size distribution of fullerenol nanoparticles in cell culture medium and their influence on antioxidative enzymes in Chinese hamster ovary cells

    Directory of Open Access Journals (Sweden)

    Srđenović Branislava U.

    2015-01-01

    Full Text Available Fullerenol (C60(OH24 nanoparticles (FNP have a significant role in biomedical research due to their numerous biological activities, some of which are cytoprotective and antioxidative properties. The aim of this study was to measure distribution of fullerenol nanoparticles and zeta potential in cell medium RPMI 1640 with 10% fetal bovine serum (FBS and to investigate the influence of FNP on Chinese hamster ovary cells (CHO-K1 survival, as well as to determine the activity of three antioxidative enzymes: superoxide-dismutase, glutathione-reductase and glutathione-S-transferase in mitomycin C-treated cell line. Our investigation implies that FNP, as a strong antioxidant, influence the cellular redox state and enzyme activities and thus may reduce cell proliferation, which confirms that FNP could be exploited for its use as a cytoprotective agent.[Projekat Ministarstva nauke Republike Srbije, br. III45005 i Pokrajinski Sekretarijat za nauku i tehnološki razvoj Vojvodine, grant number 114-451-2056/2011-01

  20. Interlaboratory studies with the Chinese hamster V79 cell metabolic cooperation assay to detect tumor-promoting agents

    Energy Technology Data Exchange (ETDEWEB)

    Bohrman, J.S.; Burg, J.R.; Elmore, E.; Gulati, D.K.; Barfknecht, T.R.; Niemeier, R.W.; Dames, B.L.; Toraason, M.; Langenbach, R.

    1988-01-01

    Three laboratories participated in an interlaboratory study to evaluate the usefulness of the Chinese hamster V79 cell metabolic cooperation assay to predict the tumor-promoting activity of selected chemical. Twenty-three chemicals of different chemical structures (phorbol esters, barbiturates, phenols, artificial sweeteners, alkanes, and peroxides) were chosen for testing based on in vivo promotion activities, as reported in the literature. Assay protocols and materials were standardized, and the chemicals were coded to facilitate unbiased evaluation. A chemical was tested only once in each laboratory, with one of the three laboratories testing only 15 out of 23 chemicals. Dunnett's test was used for statistical analysis. Chemicals were scored as positive (at least two concentration levels statistically different than control), equivocal (only one concentration statistically different), or negative. For 15 chemicals tested in all three laboratories, there was complete agreement among the laboratories for nine chemicals. For the 23 chemicals tested in only two laboratories, there was agreement on 16 chemicals. With the exception of the peroxides and alkanes, the metabolic cooperation data were in general agreement with in vivo data. However, an overall evaluation of the V79 cell system for predicting in vivo promotion activity was difficult because of the organ specificity of certain chemicals and/or the limited number of adequately tested nonpromoting chemicals.

  1. Expression of secreted recombinant human insulin-like growth factor-II (IGF-II) in Chinese hamster ovary cells.

    Science.gov (United States)

    Bekkari, H; Sekkat, D; Straczek, J; Hess, K; Belleville-Nabet, F; Nabet, P

    1994-07-29

    Chinese hamster ovary (CHO-KI) cells were cotransfected with a plasmid pcDNAI containing the human preproinsulin-like growth factor II cDNA linked downstream to the human cytomegalovirus promoter and with a plasmid containing the neomycin resistance gene (pMAM-neo). CHO neo+ were selected by growth in medium supplemented with G418 geneticin. After amplification, the neomycin-resistant clones were screened for IGF-II production. IGF-II produced was identified by dot blot and quantified by ELISA. The clones C24, C40 and C94 secreted IGF-II at about 350-400 ng per 10(6) cells per day. DNA analysis of C24 and C40 CHO cells by PCR demonstrated the presence of the IGF-II construct in the transfected cells, presumably integrated into the chromosomal DNA. IGF-II produced by CHO cells and purified by RP-HPLC was a mitogen for MCF-7 stimulating mitosis 2-fold. PMID:7765161

  2. Anticancer Effects of Fusion Protein CAtin on DMBA-induced Carcinogenesis in Buccal Pouch of Chinese Hamster

    Institute of Scientific and Technical Information of China (English)

    BAI Jie-ying; LI Xiao; LI Chang; ZHANG Xiao-fei; LI Zhi-xin; ZHAO Shuang; LIU Xiao; ZENG Lin; CHI Bao-rong

    2012-01-01

    Aberrant expression ofcarcinoembryonic antigen(CEA)is a common feature for multiple types of cancer,which makes it an attractive target for anticancer therapy.CAtin is a novel dual cancer-specific fusion protein,composed of an anti-CEA single-chain disulfide-stabilized Fv antibody(scdsFv)and Apoptin,a tumor-specific apoptosis-inducing protein.Oral squamous cell carcinoma(OSCC)is an important healthcare problem in the clinic.To evaluate the anticancer effects of CAtin on OSCC,7,12-dimethylbenz[a]anthracene(DMBA)was used to induce oral carcinogenesis and premalignant lesions in the buccal pouch of Chinese hamster,and the antitumor effects of CAtin were determined in pre-cancer,cancer and post-operatative cancer models,respectively.The results show that the administration of CAtin delayed the malignant transformation of early stage cancerous lesions,inhibited the growth of established solid oral tumors and reduced the post-operatative relapse of lesions,with no significant systemic toxicity.This study demonstrates that CAtin may have potential for the treatment of OSCC,and the development of preventive strategies based on CAtin may offer a practical approach for the treatment of human oral tumors.

  3. Effects of 2'-chlorothymidine on Chinese hamster cells irradiated with x-rays and ultraviolet light

    International Nuclear Information System (INIS)

    Effects of 2'-chlorothymidine (2'-Cl-TdR) and its mother compound, thymidine (TdR), on cell killing induced by X- and UV-irradiation have been investigated. Chinse hamster V-79 (TK+) cells as well as thymidine kinase deficient (TK-) variant cells, which were isolated from parental V-79 cells following stepwise treatment with BUdR, were incubated in a medium containing 2'-Cl-TdR and TdR after X- and UV-irradiation. In the TK+ cells, both 2'-Cl-TdR and TdR enhanced the killing efficiency of X-rays and ultraviolet light. On the other hand, in the TK- cells, only 2'-Cl-TdR enhanced the killing efficiency of X- and UV-irradiation, and no effect of TdR was observed. These results suggest that phosphorylation of TdR by the enzyme is essential for its ability to modify radiation response, while the enhancement of cell killing by 2'-Cl-TdR must be explained by a mechanism at least partly independent of phosphorylation. (author)

  4. Effects of turmeric and its active principle, curcumin, on bleomycin-induced chromosome aberrations in Chinese hamster ovary cells

    Directory of Open Access Journals (Sweden)

    Maria Cristina P. Araújo

    1999-09-01

    Full Text Available Naturally occurring antioxidants have been extensively studied for their capacity to protect organisms and cells from oxidative damage. Many plant constituents including turmeric and curcumin appear to be potent antimutagens and antioxidants. The effects of turmeric and curcumin on chromosomal aberration frequencies induced by the radiomimetic agent bleomycin (BLM were investigated in Chinese hamster ovary (CHO cells. Three concentrations of each drug, turmeric (100, 250 and 500 mg/ml and curcumin (2.5, 5 and 10 mg/ml, were combined with BLM (10 mg/ml in CHO cells treated during the G1/S, S or G2/S phases of the cell cycle. Neither turmeric nor curcumin prevented BLM-induced chromosomal damage in any phases of the cell cycle. Conversely, a potentiation of the clastogenicity of BLM by curcumin was clearly observed in cells treated during the S and G2/S phases. Curcumin was also clastogenic by itself at 10 µg/ml in two protocols used. However, the exact mechanism by which curcumin produced clastogenic and potentiating effects remains unknown.Antioxidantes de ocorrência natural têm sido exaustivamente estudados quanto a sua capacidade de proteger organimos e células contra danos oxidativos. Muitos constituintes das plantas, incluindo cúrcuma e curcumina, parecem ser potentes antimutágenos e antioxidantes. Os efeitos de cúrcuma e curcumina na freqüência de aberrações cromossômicas induzidas pelo agente radiomimético bleomicina (BLM foram investigados em células do ovário de hamster chinês (CHO. Três concentrações de cada droga, cúrcuma (100, 250 e 500 mg/ml e curcumina (2,5, 5,0 e 10 mg/ml, foram combinadas com BLM (10 mg/ml em células CHO tratadas durante as fases G1/S, S ou G2/S do ciclo celular. Nem cúrcuma nem curcumina evitaram o dano cromossômico induzido pela BLM em fase alguma do ciclo celular. Ao contrário, a potenciação da clastogenicidade da BLM pelo curcumina foi nitidamente observada em células tratadas

  5. Bystander responses in cells models; targets, dosimetry and mechanisms

    International Nuclear Information System (INIS)

    The use of microbeam approaches has been a major advance in probing the relevance of bystander responses in cell and tissue models. Our own studies at the Gray Cancer Institute have used both a charged particle microbeam, producing protons and helium ions and a soft X-ray microprobe, delivering focused carbon-K, aluminium-K and titanium-K soft X-rays. Using these techniques we have been able to build up a comprehensive picture of the underlying differences between bystander responses and direct effects in cell and tissue-like models. What is now clear is that bystander dose-response relationships, the underlying mechanisms of action and the targets involved are not the same as those observed for direct irradiation of DNA in the nucleus. Our recent studies have shown bystander responses induced in human or hamster cells even when radiation is deposited away from the nucleus in cytoplasmic targets either after charged particle or soft X-ray exposure. Importantly, the level of bystander effect, measured as cell killing was similar to that observed when the same amount of energy was deposited but targeted to the nucleus. In other studies, we have shown that underlying determination of the level of response is the energy deposited in a single cell rather than the number of cells hit. Also the overall response at low doses may be dominated by bystander signaling. These observations have significance for our understanding of radiation risk at low doses including those of environmental exposures and the applicability of the Linear Non Threshold model. The realization that cell to cell signaling is important for radiation response may also open up new therapeutic opportunities to either improve tumor cell kill or protect normal tissues if the pathways underpinning bystander signaling can be elucidated and controlled

  6. The effects of differential polyadenylation on expression of the dihydrofolate reductase-encoding gene in Chinese hamster lung cells.

    Science.gov (United States)

    Yang, H; Hussain, A; Melera, P W

    1995-10-01

    Three differently sized mRNAs are expressed from each of two DHFR (encoding dihydrofolate reductase) alleles present in the Chinese hamster lung (CHL) cell line, DC-3F. The relative abundancy of the transcripts produced from each allele differs dramatically as a result of differential utilization of the multiple poly(A) sites present in the DHFR DHFR gene and a genetic polymorphism located within the third poly(A) signal of one allele. We sought to determine whether such differences in polyadenylation affect the steady-state levels of DHFR and mRNAs expressed from either allele and, in a more general sense, to ask whether differences in 3' end RNA processing in a gene containing multiple poly(A) sites affects the final level of gene expression. An SV40 promoter-based transient expression system producing chimeric cat::DHFR transcripts was developed to regenerate the in vivo mRNA polyadenylation patterns associated with each of the two DHFR alleles. The results demonstrate that the total amount of polyadenylated RNA expressed from each of these constructs in vitro is the same regardless of the differential utilization of the poly(A) signals that occurs between them. Moreover, measurement of the individual turnover rates of the DHFR mRNAs expressed in vivo from each allele, as determined by pulse-chase labeling and actinomycin D inhibition studies, revealed no significant allele-specific differences in transcript half-lives. Finally, measuring the steady-state levels of DHFR poly(A)+ mRNA in parental DC-3F cells demonstrated that both alleles are expressed to the same extent during normal growth. Thus, even though dramatic allele-specific differences in 3' end processing of DHFR transcripts occur in vivo, such differences do not appear to influence the steady-state levels of DHFR gene expression. PMID:7590264

  7. Model-directed engineering of "difficult-to-express" monoclonal antibody production by Chinese hamster ovary cells.

    Science.gov (United States)

    Pybus, Leon P; Dean, Greg; West, Nathan R; Smith, Andrew; Daramola, Olalekan; Field, Ray; Wilkinson, Stephen J; James, David C

    2014-02-01

    Despite improvements in volumetric titer for monoclonal antibody (MAb) production processes using Chinese hamster ovary (CHO) cells, some "difficult-to-express" (DTE) MAbs inexplicably reach much lower process titers. These DTE MAbs require intensive cell line and process development activity, rendering them more costly or even unsuitable to manufacture. To rapidly and rationally identify an optimal strategy to improve production of DTE MAbs, we have developed an engineering design platform combining high-yielding transient production, empirical modeling of MAb synthesis incorporating an unfolded protein response (UPR) regulatory loop with directed expression and cell engineering approaches. Utilizing a panel of eight IgG1 λ MAbs varying >4-fold in volumetric titer, we showed that MAb-specific limitations on folding and assembly rate functioned to induce a proportionate UPR in host CHO cells with a corresponding reduction in cell growth rate. Derived from comparative empirical modeling of cellular constraints on the production of each MAb we employed two strategies to increase production of DTE MAbs designed to avoid UPR induction through an improvement in the rate/cellular capacity for MAb folding and assembly reactions. Firstly, we altered the transfected LC:HC gene ratio and secondly, we co-expressed a variety of molecular chaperones, foldases or UPR transactivators (BiP, CypB, PDI, and active forms of ATF6 and XBP1) with recombinant MAbs. DTE MAb production was significantly improved by both strategies, although the mode of action was dependent upon the approach employed. Increased LC:HC ratio or CypB co-expression improved cell growth with no effect on qP. In contrast, BiP, ATF6c and XBP1s co-expression increased qP and reduced cell growth. This study demonstrates that expression-engineering strategies to improve production of DTE proteins in mammalian cells should be product specific, and based on rapid predictive tools to assess the relative impact of

  8. Protective effect of propolis on radiation-induced chromosomal damage on Chinese hamster ovary cells (CHO-K1)

    International Nuclear Information System (INIS)

    In the last years, particular interest has been given to investigations concerning natural, effective and nontoxic compounds with radioprotective capacity in concert with increasing utilization of different types of ionizing radiation for various applications. Among them, propolis, a resinous mixture of substances collected by honey bees (Apis mellifera) has been considered promising since it presents several advantageous characteristics, i.e., antiinflammatory, anticarcinogenic, antimicrobial and free radical scavenging action. It is, therefore, a direct antioxidant that protects cells and organisms from the adverse effects of ionizing radiation. These relevant biological activities are mainly mediated by the flavonoids, present at relatively high concentrations in the propolis. Considering that the chemical composition and, consequently, the biological activity of propolis is variable according to the environmental plant ecology, the present study was conducted in order to evaluate the radioprotective capacity of Brazilian propolis, collected in the State of Rio Grande do Sul, against genotoxic damages induced by 60Co γ-radiation in Chinese hamster ovary cells (CHO-K1). for this purpose, micronucleus induction was analyzed concerning irreparable damage, specifically related to DNA double-strand breaks, that are potentially carcinogenic. CHO-K1 cells were submitted to different concentrations of propolis (3 - 33 μg/ml), 1 h before irradiation, with 1 Gy of γ radiation (0.722 Gy/min). The data obtained showed a decreasing tendency in the quantity of radioinduced damage on cells previously treated with propolis. The radioprotective effect was more prominent at higher propolis concentration. The treatment with propolis alone did not induce genotoxic effects on CHO-K1 cells. Beside that, the treatment with propolis, associated or not with radiation, did not influence the kinetics of cellular proliferation. (author)

  9. Activation of two new alpha(1,3)fucosyltransferase activities in Chinese hamster ovary cells by 5-azacytidine.

    Science.gov (United States)

    Potvin, B; Stanley, P

    1991-01-01

    Several mammalian alpha(1,3)fucosyltransferases (alpha[1,3]Fuc-T) that synthesize carbohydrates containing alpha(1,3)fucosylated lactosamine units have been identified. Although Chinese hamster ovary (CHO) cells do not express alpha(1,3)Fuc-T activity, the rare mutants LEC11 and LEC12, isolated after mutagenesis or DNA transfection, each express an alpha(1,3)Fuc-T that may be distinguished by several criteria. Two new CHO mutants possessing alpha(1,3)Fuc-T activity (LEC29 and LEC30) have now been isolated after treatment of a CHO cell population with 5-azacytidine (5-AzaC), ethylnitrosourea (ENU), or 5-AzaC followed by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Like LEC12, both mutants possess an N-ethylmaleimide-resistant alpha(1,3)Fuc-T activity that can utilize a variety of acceptors and both express the Lewis X (Lex) determinant (Gal beta[1,4](Fuc alpha[1,3])GlcNAc beta 1)) but not the sialyl alpha(2,3)Lex determinant on cell-surface carbohydrates. However, LEC29 and LEC30 may be distinguished from LEC11 and LEC12, as well as from each other, on the basis of their unique patterns of lectin resistance and their abilities to bind the VIM-2 monoclonal antibody that recognizes carbohydrates terminating in NeuNAc alpha(2,3)Gal beta(1,4)GlcNAc beta(1,3)Gal beta(1,4)(Fuc alpha[1,3])GlcNAc beta and also by the different in vitro substrate specificities and kinetic properties of their respective alpha(1,3)Fuc-T activities. The combined data provide good evidence that the LEC29 and LEC30 alpha(1,3)Fuc-Ts are novel transferases encoded by distinct gene products. PMID:1724918

  10. Conditional expression of full-length humanized anti-prion protein antibodies in Chinese hamster ovary cells.

    Science.gov (United States)

    Mueller, Daniel A; Heinig, Lars; Ramljak, Sanja; Krueger, Astrid; Schulte, Reiner; Wrede, Arne; Stuke, Andreas W

    2010-12-01

    Because of their high antigen specificity and metabolic stability, genetically engineered human monoclonal antibodies are on the way to becoming one of the most promising medical diagnostics and therapeutics. In order to establish an in vitro system capable of producing such biosimilar antibodies, we used human constant chain sequences to design the novel human antibody expressing vector cassette pMAB-ABX. A bidirectional tetracycline (tet)-controllable promotor was used for harmonized expression of immunoglobulin type G (IgG) heavy and light chains. As an example we used anti-prion protein (anti-PrP) IgGs. Therefore, the variable heavy (V(H)) and light chain (V(L)) sequences of anti-PrP antibodies, previously generated in our laboratory by DNA immunization of prion protein knock-out mice, were isolated from murine hybridoma cell lines and inserted into pMAB-ABX vector. After transfection of Chinese hamster ovary (CHO) cells, a number of stable antibody producing cell clones were selected. One cell line (pMAB-ABX-13F10/3B5) stably expressing the recombinant humanized antibody (rechuAb) 13F10/3B5 was selected for detailed characterization by Western blot, immunofluorescence, and flow cytometric analyses. The full-length recombinant humanized IgG antibody showed a high level of expression in the cytoplasm. In conclusion, the new cell system described here is a suitable tool to produce functional intact full-length humanized IgG antibodies. PMID:21087094

  11. Molecular structural analysis of HPRT mutations induced by thermal and epithermal neutrons in Chinese hamster ovary cells.

    Science.gov (United States)

    Kinashi, Y; Sakurai, Y; Masunaga, S; Suzuki, M; Takagaki, M; Akaboshi, M; Ono, K

    2000-09-01

    Chinese hamster ovary (CHO) cells were exposed to thermal and epithermal neutrons, and the occurrence of mutations at the HPRT locus was investigated. The Kyoto University Research Reactor (KUR), which has been improved for use in neutron capture therapy, was the neutron source. Neutron energy spectra ranging from nearly pure thermal to epithermal can be chosen using the spectrum shifters and thermal neutron filters. To determine mutant frequency and cell survival, cells were irradiated with thermal and epithermal neutrons under three conditions: thermal neutron mode, mixed mode with thermal and epithermal neutrons, and epithermal neutron mode. The mutagenicity was different among the three irradiation modes, with the epithermal neutrons showing a mutation frequency about 5-fold that of the thermal neutrons and about 1.5-fold that of the mixed mode. In the thermal neutron and mixed mode, boron did not significantly increase the frequency of the mutants at the same dose. Therefore, the effect of boron as used in boron neutron capture therapy (BNCT) is quantitatively minimal in terms of mutation induction. Over 300 independent neutron-induced mutant clones were isolated from 12 experiments. The molecular structure of HPRT mutations was determined by analysis of all nine exons by multiplex polymerase chain reaction. In the thermal neutron and mixed modes, total and partial deletions were dominant and the fraction of total deletions was increased in the presence of boron. In the epithermal neutron mode, more than half of the mutations observed were total deletions. Our results suggest that there are clear differences between thermal and epithermal neutron beams in their mutagenicity and in the structural pattern of the mutants that they induce. Mapping of deletion breakpoints of 173 partial-deletion mutants showed that regions of introns 3-4, 7/8-9 and 9-0 are sensitive to the induction of mutants by neutron irradiation.

  12. Oxygen and exposure kinetics as factors influencing the cytotoxicity of porfiromycin, a mitomycin C analogue, in Chinese hamster ovary cells.

    Science.gov (United States)

    Marshall, R S; Rauth, A M

    1988-10-15

    Some factors affecting the cytotoxicity of porfiromycin (PM), an analogue of mitomycin C (MMC), were investigated in suspension cultures of wild-type (AA8-4) and repair-deficient (UV-20) Chinese hamster ovary cells. Oxygen was an important modulator of PM toxicity in AA8-4 cells. The aerobic toxicity was significantly less, and toxicity under extremely hypoxic conditions was significantly greater for PM than MMC. Porfiromycin cytotoxicity at intermediate O2 levels was similar to that observed previously for MMC. While the aerobic/hypoxic ratio was greater for PM than MMC, survival at intermediate oxygen concentrations could limit the therapeutic utility of these drugs as adjuncts to radiotherapy. Ascorbic acid was found to increase the aerobic, but not hypoxic, cytotoxicity of PM in AA8-4 cells, as was observed previously for MMC. Investigation of various exposure times and drug concentrations revealed that drug toxicity for both aerobic and hypoxic cells was dependent on the product of drug concentration and time, and that the aerobic/hypoxic differential observed in AA8-4 cells was constant over a broad range of exposure conditions. The sensitivity of UV-20 cells was also a linear function of concentration and time, but no aerobic/hypoxic differential was observed in these cells. It is suggested that the sensitivity of UV-20 to PM and MMC, and its lack of an hypoxic/aerobic differential could result from lethality being due to a different lesion than in wild-type cells. PMID:3167822

  13. Up-regulation of ROS by mitochondria-dependent bystander signaling contributes to genotoxicity of bystander effects

    International Nuclear Information System (INIS)

    Genomic instability can be observed in bystander cells. However, the underlying mechanism(s) is still relatively unclear. In a previous study, we found that irradiated cells released mitochondria-dependent intracellular factor(s) which could lead to bystander γ-H2AX induction. In this paper, we used normal (ρ+) and mtDNA-depleted (ρ0) human-hamster hybrid cells to investigate mitochondrial effects on the genotoxicity in bystander effect through medium transfer experiments. Through the detection of DNA double-strand breaks with γ-H2AX, we found that the fraction of γ-H2AX positive cells changed with time when irradiation conditioned cell medium (ICCM) were harvested. ICCM harvested from irradiated ρ+ cells at 10 min post-irradiation (ρ+ ICCM10min) caused larger increases of bystander γ-H2AX induction comparing to ρ0 ICCM10min, which only caused a slight increase of bystander γ-H2AX induction. The ρ+ ICCM10min could also result in the up-regulation of ROS production (increased by 35% at 10 min), while there was no significant increase in cells treated with ρ0 ICCM10min. We treated cells with dimethyl sulfoxide (DMSO), the scavenger of ROS, and quenched γ-H2AX induction by ρ+ ICCM. Furthermore, after the medium had been transferred and the cells were continuously cultured for 7 days, we found significantly increased CD59- gene loci mutation (increased by 45.9%) and delayed cell death in the progeny of ρ+ ICCM-treated bystander cells. In conclusion, the work presented here suggested that up-regulation of the mitochondria-dependent ROS might be very important in mediating genotoxicity of bystander effects.

  14. Up-regulation of ROS by mitochondria-dependent bystander signaling contributes to genotoxicity of bystander effects

    Energy Technology Data Exchange (ETDEWEB)

    Chen Shaopeng [Key Laboratory of Ion Beam Bioengineering, Institute of Plasma Physics, Chinese Academy of Sciences, Hefei 230031 (China); Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong); Zhao Ye; Zhao Guoping [Key Laboratory of Ion Beam Bioengineering, Institute of Plasma Physics, Chinese Academy of Sciences, Hefei 230031 (China); Han Wei [Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong); Bao Lingzhi [Key Laboratory of Ion Beam Bioengineering, Institute of Plasma Physics, Chinese Academy of Sciences, Hefei 230031 (China); Yu, K.N., E-mail: peter.yu@cityu.edu.hk [Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong); Wu Lijun, E-mail: ljw@ipp.ac.cn [Key Laboratory of Ion Beam Bioengineering, Institute of Plasma Physics, Chinese Academy of Sciences, Hefei 230031 (China)

    2009-06-18

    Genomic instability can be observed in bystander cells. However, the underlying mechanism(s) is still relatively unclear. In a previous study, we found that irradiated cells released mitochondria-dependent intracellular factor(s) which could lead to bystander {gamma}-H2AX induction. In this paper, we used normal ({rho}{sup +}) and mtDNA-depleted ({rho}{sup 0}) human-hamster hybrid cells to investigate mitochondrial effects on the genotoxicity in bystander effect through medium transfer experiments. Through the detection of DNA double-strand breaks with {gamma}-H2AX, we found that the fraction of {gamma}-H2AX positive cells changed with time when irradiation conditioned cell medium (ICCM) were harvested. ICCM harvested from irradiated {rho}{sup +} cells at 10 min post-irradiation ({rho}{sup +} ICCM{sub 10min}) caused larger increases of bystander {gamma}-H2AX induction comparing to {rho}{sup 0} ICCM{sub 10min}, which only caused a slight increase of bystander {gamma}-H2AX induction. The {rho}{sup +} ICCM{sub 10min} could also result in the up-regulation of ROS production (increased by 35% at 10 min), while there was no significant increase in cells treated with {rho}{sup 0} ICCM{sub 10min}. We treated cells with dimethyl sulfoxide (DMSO), the scavenger of ROS, and quenched {gamma}-H2AX induction by {rho}{sup +} ICCM. Furthermore, after the medium had been transferred and the cells were continuously cultured for 7 days, we found significantly increased CD59{sup -} gene loci mutation (increased by 45.9%) and delayed cell death in the progeny of {rho}{sup +} ICCM-treated bystander cells. In conclusion, the work presented here suggested that up-regulation of the mitochondria-dependent ROS might be very important in mediating genotoxicity of bystander effects.

  15. Effects of clonal variation on growth, metabolism, and productivity in response to trophic factor stimulation: a study of Chinese hamster ovary cells producing a recombinant monoclonal antibody

    OpenAIRE

    Dahodwala, Hussain; Nowey, Mark; Mitina, Tatyana; Sharfstein, Susan T.

    2011-01-01

    The growth, metabolism, and productivity of five Chinese hamster ovary (CHO) clones were explored in response to stimulation with insulin (5 mg/L) and LONG®R3IGF-I (20 μg/L or 100 μg/L). All five clones were derived from the same parental CHO cell line (DG44) and produced the same recombinant monoclonal antibody, with varying specific productivities. There was no uniform response among the clones to stimulation with the different trophic factors. One of the high productivity clones (clone D) ...

  16. Restoration of Chinese hamster cell radiation resistance by the human repair gene ERCC-5 and progress in molecular cloning of this gene

    International Nuclear Information System (INIS)

    The uv-sensitive Chinese hamster cell uv-135 is being used to identify and isolate the human gene, ERCC-5, which corrects nucleotide excision repair in this incision-defective mutant. A cosmid library, constructed from a 30 transformant of uv-135, has been screened for transfected gpt and human Alu family sequences. An ordered physical map of overlapping positives cosmids has been determined. Molecular evidence suggests a region of this map of <40 Kbp contains the ERCC-5 gene. 10 refs., 2 figs

  17. Genetic determinants of growth phase-dependent and adenovirus 5-responsive expression of the Chinese hamster thymidine kinase gene are contained within thymidine kinase mRNA sequences.

    OpenAIRE

    Lewis, J. A.; Matkovich, D A

    1986-01-01

    We have constructed a chimeric thymidine kinase (TK) minigene, pHe delta 6Ha, which combines the complete coding and 3' noncoding regions of a Chinese hamster TK cDNA with the promoter region and 5' untranslated region of the TK gene of herpes simplex virus type 1. We have transformed rat 4 cells to Tk+ with this gene and analyzed the pattern of TK gene expression in these transformants under various conditions of in vitro cell culture. We find that TK gene expression in these Tk+ transforman...

  18. Differential toxicity of mitomycin C and porfiromycin to aerobic and hypoxic Chinese hamster ovary cells overexpressing human NADPH:cytochrome c (P-450) reductase.

    OpenAIRE

    Belcourt, M F; Hodnick, W F; Rockwell, S; Sartorelli, A C

    1996-01-01

    Purified NADPH:cytochrome c (P-450) reductase (FpT; NADPH-ferrihemoprotein oxidoreductase, EC 1.6.2.4) can reductively activate mitomycin antibiotics through a one-electron reduction to species that alkylate DNA. To assess the involvement of FpT in the intracellular activation of the mitomycins, transfectants overexpressing a human FpT cDNA were established from a Chinese hamster ovary cell line deficient in dihydrofolate reductase (CHO-K1/dhfr-). The parental cell line was equisensitive to t...

  19. Role of 239Pu-induced chromosome alterations and mutated Ki-v-ras oncogene during liver-cancer induction in Chinese hamsters and mice

    International Nuclear Information System (INIS)

    Chromosome aberrations and mutated oncogenes can cause important changes during carcinogenesis. Model systems are being studied in which defined cellular and molecular changes can be quantitated and altered, and tumor frequency, type, and time of appearance can be evaluated. Dose-response relationships for Pu Citrate-induced chromosome aberrations and liver cancer were measured in Chinese hamsters. Chromosome aberrations increased linearly according to dose, with a slope of 4.8 x 10-1 aberrations/cell/Gy; liver-tumor incidence was 1.1 x 10-1 tumors/animal/Gy. The dose was calculated at the 50% survival time. The interaction between Pu and Ki-v-ras, an altered, dominant-acting oncogene, on the induction of liver cancer was measured in B6C3F1 mice. The neo oncogene was used as a negative control in these studies. The Ki-v-ras oncogene was inserted into a viral vector and incorporated into the livers of mice either 30 days before or after the incorporation of 239Pu. Compared with both the controls and the mice injected with a single insult, mortality increased in groups of animals that received combined exposure to oncogenes, CCl4, and 239Pu. The relationships between molecular and cellular damage and the induction of cancer is being defined in both mice and Chinese hamsters

  20. Protective Effect of Boric Acid on Oxidative DNA Damage In Chinese Hamster Lung Fibroblast V79 Cell Lines

    Directory of Open Access Journals (Sweden)

    SezenYılmaz

    2016-02-01

    Full Text Available Objective: Many studies have been published on the antioxidative effects of boric acid (BA and sodium borates in in vitro studies. However, the boron (B concentrations tested in these in vitro studies have not been selected by taking into account the realistic blood B concentrations in humans due to the lack of comprehensive epidemiological studies. The recently published epidemiological studies on B exposure conducted in China and Turkey provided blood B concentrations for both humans in daily life and workers under extreme exposure conditions in occupational setting. The results of these studies have made it possible to test antioxidative effects of BA in in vitro studies within the concentration range relevant to humans. The aim of this study was to investigate the protective effects of BA against oxidative DNA damage in V79 (Chinese hamster lung fibroblast cells. The concentrations of BA tested for its protective effect was selected by taking the blood B concentrations into account reported in previously published epidemiological studies. Therefore, the concentrations of BA tested in this study represent the exposure levels for humans in both daily life and occupational settings. Materials and Methods: In this experimental study, comet assay and neutral red uptake (NRU assay methods were used to determinacy to toxicity and genotoxicity of BA and hydrogen peroxide (H2O2. Results: The results of the NRU assay showed that BA was not cytotoxic within the tested concentrations (3, 10, 30, 100 and 200 μM. These non-cytotoxic concentrations were used for comet assay. BA pre-treatment significantly reduced (P<0.05, one-way ANOVA the DNA damaging capacity of H2O2 at each tested BA concentrations in V79 cells. Conclusion: Consequently, pre-incubation of V79 cells with BA has significantly reduced the H2O2-induced oxidative DNA damage in V79 cells. The protective effect of BA against oxidative DNA damage in V79 cells at 5, 10, 50, 100 and 200 μM (54

  1. Establishment and Identification of Chinese Hamster Ovary Cell Lines with Stable Expression of Soluble CD40 Ligands

    Directory of Open Access Journals (Sweden)

    JIANG Hua-wei

    2014-09-01

    Full Text Available Objective: To establish the Chinese Hamster Ovary (CHO cell lines with stable expression of soluble CD40 ligands (sCD40L. Methods: Recombinant plasmid pIRES2-EGFP-sCD40L, enzyme digestion and sequencing identification were obtained by cloning sCD40L coding sequences into eukaryotic expression vector pIRES2-EGFP from carrier pDC316-sCD40 containing sCD40L. CHO cells were transfected by electroporation, followed by screening of resistant clones with G418, after which monoclones were obtained by limited dilution assay and multiply cultured. Flow cytometer and reverted fluorescence microscope were applied to observe the expression of green fluorescent protein, while sCD40L expression was detected by polymerase chain reaction (PCR, reverse transcription-polymerase chain reaction (RT-PCR and enzyme-linked immunosorbent assay (ELISA from aspects of deoxyribose nucleic acid (DNA, messenger ribonucleic acid (mRNA and protein, respectively. CHO-sCD40L was cultured together with MDA-MB-231 cells to compare the expression changes of surface molecule fatty acid synthase (Fas by flow cytometer and observe the apoptosis of MDA-MB-231 cells after Fas activated antibodies (CH-11 were added 24 h later. Results: Plasmid pIRES2-EGFP-sCD40L was successfully established, and cell lines with stable expression of sCD40L were obtained with cloned culture after CHO cell transfection, which was named as B11. Flow cytometer and reverted fluorescence microscope showed >90% expression of green fluorescent protein, while PCR, RT-PCR and ELISA suggested integration of sCD40L genes into cell genome DNA, transcription of sCD40L mRNA and sCD40L protein expression being (4.5±2.1 ng/mL in the supernatant of cell culture, respectively. After co-culture of B11 and MDA-MB-231 cells, the surface Fas expression of MDA-MB-231 cells was increased from (3±1.02 % to (34.8±8.75%, while the apoptosis rate 24 h after addition of CH11 from (5.4±1.32% to (20.7±5.24%, and the differences

  2. Lack of Bystander Effects From High LET Radiation For Early Cytogenetic Endpoints.

    Energy Technology Data Exchange (ETDEWEB)

    Groesser, Torsten; Cooper, Brian; Rydberg, Bjorn

    2008-05-07

    The aim of this work was to study radiation-induced bystander effects for early cytogenetic end points in various cell lines using the medium transfer technique after exposure to high- and low-LET radiation. Cells were exposed to 20 MeV/ nucleon nitrogen ions, 968 MeV/nucleon iron ions, or 575 MeV/nucleon iron ions followed by transfer of the conditioned medium from the irradiated cells to unirradiated test cells. The effects studied included DNA double-strand break induction, {gamma}-H2AX focus formation, induction of chromatid breaks in prematurely condensed chromosomes, and micronucleus formation using DNA repair-proficient and -deficient hamster and human cell lines (xrs6, V79, SW48, MO59K and MO59J). Cell survival was also measured in SW48 bystander cells using X rays. Although it was occasionally possible to detect an increase in chromatid break levels using nitrogen ions and to see a higher number of {gamma}-H2AX foci using nitrogen and iron ions in xrs6 bystander cells in single experiments, the results were not reproducible. After we pooled all the data, we could not verify a significant bystander effect for any of these end points. Also, we did not detect a significant bystander effect for DSB induction or micronucleus formation in these cell lines or for clonogenic survival in SW48 cells. The data suggest that DNA damage and cytogenetic changes are not induced in bystander cells. In contrast, data in the literature show pronounced bystander effects in a variety of cell lines, including clonogenic survival in SW48 cells and induction of chromatid breaks and micronuclei in hamster cells. To reconcile these conflicting data, it is possible that the epigenetic status of the specific cell line or the precise culture conditions and medium supplements, such as serum, may be critical for inducing bystander effects.

  3. Intracellular Transactivation of Epidermal Growth Factor Receptor by alpha(1A)-Adrenoceptor Is Mediated by Phosphatidylinositol 3-Kinase Independently of Activation of Extracellular Signal Regulated Kinases 1/2 and Serine-Threonine Kinases in Chinese Hamster Ovary Cells

    NARCIS (Netherlands)

    Ulu, Nadir; Henning, Robert H.; Guner, Sahika; Zoto, Teuta; Duman-Dalkilic, Basak; Duin, Marry; Gurdal, Hakan

    2013-01-01

    Transactivation of epidermal growth factor receptor (EGFR) by alpha(1)-adrenoceptor (alpha(1)-AR) is implicated in contraction and hypertrophy of vascular smooth muscle (VSM). We examine whether all alpha(1)-AR subtypes transactivate EGFR and explore the mechanism of transactivation. Chinese hamster

  4. Cytotoxicity and DNA lesions produced by mitomycin C and porfiromycin in hypoxic and aerobic EMT6 and Chinese hamster ovary cells.

    Science.gov (United States)

    Fracasso, P M; Sartorelli, A C

    1986-08-01

    Solid neoplasms may contain deficient or poorly functional vascular beds, a property that leads to the formation of hypoxic tumor cells, which form a therapeutically resistant cell population within the tumor that is difficult to eradicate by ionizing irradiation and most existing chemotherapeutic agents. As an approach to the therapeutic attack of hypoxic cells, we have measured the cytotoxicity and DNA lesions produced by the bioreductive alkylating agents mitomycin C and porfiromycin, two structurally similar antibiotics, in oxygen-deficient and aerobic cells. Mitomycin C and porfiromycin were preferentially cytotoxic to hypoxic EMT6 cells in culture, with porfiromycin producing a greater differential kill of hypoxic EMT6 cells relative to their oxygenated counterparts than did mitomycin C. Chinese hamster ovary cells were more resistant to these quinone antibiotics; although in this cell line, porfiromycin was significantly more cytotoxic to hypoxic cells than to aerobic cells, and the degree of oxygenation did not affect the toxicity of mitomycin C. Alkaline elution methodology was utilized to study the formation of DNA single-strand breaks and DNA interstrand cross-links produced by mitomycin C and porfiromycin in both EMT6 and Chinese hamster ovary cells. A negligible quantity of DNA single-strand breaks and DNA interstrand cross-links were produced in hypoxic and aerobic Chinese hamster ovary cells by exposure to mitomycin C or porfiromycin, a finding consistent with the considerably lower sensitivity of this cell line to these agents. In EMT6 tumor cells, no single-strand breaks appeared to be produced by these antitumor antibiotics under both hypoxic and aerobic conditions; however, a significant number of DNA interstrand cross-links were formed in this cell line following drug treatment, with substantially more DNA interstrand cross-linking being produced under hypoxic conditions. Mitomycin C and porfiromycin caused the same amount of cross-linking under

  5. Induction of apoptosis by ionizing radiation in Chinese hamster V79 cells and a radioresistant cell strain derived from V79.

    Science.gov (United States)

    Ghosh, R; Sengupta, S; Bhattacharyya, N P

    1996-09-01

    DNA fragmentation into nucleosome ladder, a hall mark of apoptosis, could be obtained by as low as 0.58 Gy of gamma irradiation within 6 hr of irradiation which increased appreciably after 48 hr in V79 cells. In the same condition condensation of the nucleus and marginalization of the cytoplasm the characteristic morphology of apoptotic death were observed. Unirradiated controls had approximately 2% apoptotic cells. When cells were irradiated with 0.58 Gy, approximately 10% of the cells had the apoptotic morphology. This number increased to approximately 29% at 3.5 Gy dose. At a higher dose, apoptotic and necrotic cells were visualized. In radio resistant cells higher doses were required to induce morphological changes. The results indicated that gamma irradiation can induce apoptosis in Chinese hamster V79, fibroblast cell line and the radioresistant cell strain derived from V79 cells is also resistant to induction of apoptosis.

  6. Toxicology Studies on Lewisite and Sulfur Mustard Agents: Genetic Toxicity of Sulfur Mustard (HD) in Chinese Hamster Ovary Cells Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Jostes, Jr., R. F.; Sasser, L. B.; Rausch, R. J.

    1989-05-01

    The cytotoxic, clastogenic and mutagenic effects of sulfur nustard in Chinese hamster ovary cells are described in this reoort. The cytotoxicity data indicate that micromolar amounts of HC are highly toxic in microrolar amounts. Chromosone aberration frequencies increased in a dose-dependent manner over a dose range of 0. 5 to 1.0 {micro}m and SCE increased in a dose-dependent fashion in the dose range of 0.0625 to 0.25 {micro}M. Mutation induction at the HGPRT locus was sporadic, but the majority of the exoosures resulted in mutation frequencies which were 1.2 to 4.3 fold higher than the spontaneous frequencies.

  7. Evaluation of cytogenetic effects of a naturally occurring non-ice-nucleation Pseudomonas fluorescens strain in Chinese hamster ovary (CHO) cells.

    Science.gov (United States)

    Caruso, P; Andreozzi, L; Motta, S; Mosesso, P

    1995-01-01

    One of the main methods for eliminating ice-nucleation-active (INA+) bacteria the micro-organisms responsible for frost injuries to plants at mild freezing temperatures, is the use, as competitors, of other naturally occurring non-nucleating strains (non-INA). In the present article we investigated the cytogenetic effects of a naturally occurring non-INA strain of Pseudomonas fluorescens (MS 1640 R3), evaluating the induction of chromosomal aberrations and sister chromatid exchanges (SCEs) in Chinese hamster ovary (CHO) cells in the absence and presence of rat S9 metabolism. The results obtained did not show any increase in either chromosomal aberrations or SCEs, both in the absence and presence of rat S9 metabolism when used as i) intact bacteria cells, ii) sonicated bacteria (i.e., potential endotoxins), or iii) metabolic bacterial products (i.e., potential exotoxins) released in the growth medium. PMID:8584981

  8. The effect of oxygen on low-dose hypersensitivity and increased radioresistance in Chinese hamster V79-379A cells

    International Nuclear Information System (INIS)

    Chinese hamster V79 cells irradiated in air are hypersensitive to X-ray doses less than 0.5 Gy and show an increased radioresistance over the dose range 0.5-1 Gy. Of considerable interest from both a mechanistic and clinical viewpoint is the response of hypoxic cells over this dose range. The data presented here indicate that hypoxic cells are also hypersensitive to low X-ray doses and exhibit an increased radioresistant response, albeit triggered at a somewhat higher dose (0.69 Gy, SEM ± 0.18 Gy) than observed in oxygenated cells (0.5 Gy, SEM ± 0.21 Gy). These data indicate that the triggering event for increased radioresistance may be independent of oxygen. As reported by others previously, the oxygen enhancement ratio was found to decrease with a decreasing X-ray dose. 21 refs., 3 figs., 1 tab

  9. Bystanders Are the Key to Stopping Bullying

    Science.gov (United States)

    Padgett, Sharon; Notar, Charles E.

    2013-01-01

    Bullying is the dominance over another. Bullying occurs when there is an audience. Peer bystanders provide an audience 85% of instances of bullying. If you remove the audience bullying should stop. The article is a review of literature (2002-2013) on the role of bystanders; importance of bystanders; why bystanders behave as they do; resources to…

  10. Species differences in the immunoreactive expression of oxytocin, vasopressin, tyrosine hydroxylase and estrogen receptor alpha in the brain of Mongolian gerbils (Meriones unguiculatus and Chinese striped hamsters (Cricetulus barabensis.

    Directory of Open Access Journals (Sweden)

    Yu Wang

    Full Text Available Species differences in neurochemical expression and activity in the brain may play an important role in species-specific patterns of social behavior. In the present study, we used immunoreactive (ir labeling to compare the regional density of cells containing oxytocin (OT, vasopressin (AVP, tyrosine hydroxylase (TH, or estrogen receptor alpha (ERα staining in the brains of social Mongolian gerbils (Meriones unguiculatus and solitary Chinese striped hamsters (Cricetulus barabensis. Multiple region- and neurochemical-specific species differences were found. In the anterior hypothalamus (AH, Mongolian gerbils had higher densities of AVP-ir and ERα-ir cells than Chinese striped hamsters. In the lateral hypothalamus (LH, Mongolian gerbils also had higher densities of AVP-ir and TH-ir cells, but a lower density of OT-ir cells, than Chinese striped hamsters. Furthermore, in the anterior nucleus of the medial preoptic area (MPOAa, Mongolian gerbils had higher densities of OT-ir and AVP-ir cells than Chinese striped hamsters, and an opposite pattern was found in the posterior nucleus of the MPOA (MPOAp. Some sex differences were also observed. Females of both species had higher densities of TH-ir cells in the MPOAa and of OT-ir cells in the intermediate nucleus of the MPOA (MPOAi than males. Given the role of these neurochemicals in social behaviors, our data provide additional evidence to support the notion that species-specific patterns of neurochemical expression in the brain may be involved in species differences in social behaviors associated with different life strategies.

  11. A fucan from the brown seaweed Spatoglossum schröederi inhibits Chinese hamster ovary cell adhesion to several extracellular matrix proteins

    Directory of Open Access Journals (Sweden)

    Rocha H.A.O.

    2001-01-01

    Full Text Available Fucans, a family of sulfated polysaccharides present in brown seaweed, have several biological activities. Their use as drugs would offer the advantage of no potential risk of contamination with viruses or particles such as prions. A fucan prepared from Spatoglossum schröederi was tested as a possible inhibitor of cell-matrix interactions using wild-type Chinese hamster ovary cells (CHO-K1 and the mutant type deficient in xylosyltransferase (CHO-745. The effect of this polymer on adhesion properties with specific extracellular matrix components was studied using several matrix proteins as substrates for cell attachment. Treatment with the polymer inhibited the adhesion of fibronectin to both CHO-K1 (2 x 10(5(and CHO-745 (2 x 10(5 and 5 x 10(5 cells. No effect was detected with laminin, using the two cell types. On the other hand, adhesion to vitronectin was inhibited in CHO-K1 cells and adhesion to type I collagen was inhibited in CHO-745 cells. In spite of this inhibition, the fucan did not affect either cell proliferation or cell cycle. These results demonstrate that this polymer is a new anti-adhesive compound with potential pharmacological applications.

  12. Effect of oxygen-radiosensitizer mixtures on the radiation response of Chinese hamster cells, line V-79-753B, in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Millar, B.C.; Fielden, E.M.; Steele, J.J.

    1980-07-01

    The present data show that the maximum yield of single-strand breaks (ssb) in the cellular DNA of Chinese hamster cells V-79-753B is produced at a concentration of oxygen that produces an enhancement ratio for cell survival of 1.9. The relationship between the oxygen concentration and enhancement ratio for survival in this cell line is biphasic with a plateau at ER = 1.9 over the range of 1.5 to 7 ..mu..M O/sub 2/. For concetrations of oxygen below 1.5 ..mu..M a linear relationship between 1/D/sub 0/ and the initial yield of ssb is found. Electron affinic and free radical radiosensitizers operate by different mechanisms which are reflected at the level of ssb production; electron affinic compounds increase the yield of ssb in anoxia and in the presence of low concentrations of oxygen, whereas free radical radiosensitizers do not. The observation that TMPN can compete with oxygen or misonidazole in reactions that lead to changes in radiosensitivity but not ssb production indicates that the relationship between the two parameters must be casual and not casual.

  13. The impact of homologous recombination repair deficiency on depleted uranium clastogenicity in Chinese hamster ovary cells: XRCC3 protects cells from chromosome aberrations, but increases chromosome fragmentation.

    Science.gov (United States)

    Holmes, Amie L; Joyce, Kellie; Xie, Hong; Falank, Carolyne; Hinz, John M; Wise, John Pierce

    2014-04-01

    Depleted uranium (DU) is extensively used in both industry and military applications. The potential for civilian and military personnel exposure to DU is rising, but there are limited data on the potential health hazards of DU exposure. Previous laboratory research indicates DU is a potential carcinogen, but epidemiological studies remain inconclusive. DU is genotoxic, inducing DNA double strand breaks, chromosome damage and mutations, but the mechanisms of genotoxicity or repair pathways involved in protecting cells against DU-induced damage remain unknown. The purpose of this study was to investigate the effects of homologous recombination repair deficiency on DU-induced genotoxicity using RAD51D and XRCC3-deficient Chinese hamster ovary (CHO) cell lines. Cells deficient in XRCC3 (irs1SF) exhibited similar cytotoxicity after DU exposure compared to wild-type (AA8) and XRCC3-complemented (1SFwt8) cells, but DU induced more break-type and fusion-type lesions in XRCC3-deficient cells compared to wild-type and XRCC3-complemented cells. Surprisingly, loss of RAD51D did not affect DU-induced cytotoxicity or genotoxicity. DU induced selective X-chromosome fragmentation irrespective of RAD51D status, but loss of XRCC3 nearly eliminated fragmentation observed after DU exposure in wild-type and XRCC3-complemented cells. Thus, XRCC3, but not RAD51D, protects cells from DU-induced breaks and fusions and also plays a role in DU-induced chromosome fragmentation. PMID:24561002

  14. Understanding the intracellular effects of yeast extract on the enhancement of Fc-fusion protein production in Chinese hamster ovary cell culture.

    Science.gov (United States)

    Hu, Dongdong; Sun, Yating; Liu, Xuping; Liu, Jintao; Zhang, Xintao; Zhao, Liang; Wang, Haibin; Tan, Wen-Song; Fan, Li

    2015-10-01

    Yeast extract (YE), as a non-animal source additive for mammalian cell culture medium, has been widely used for manufacturing of therapeutic proteins. In the present study, one particular YE was found to have significantly improved the specific productivity (q p) of Fc-fusion protein in recombinant Chinese hamster ovary (rCHO) cell culture. In order to elucidate the intracellular effects of YE on protein productivity, steps of the target protein synthesis process were investigated to unveil their variations caused by YE addition. Stepwise analysis on Fc-fusion protein synthesis process showed that YE enhanced Fc-fusion protein gene transcription with cell cycle arrest at G1 phase; mammalian target of rapamycin (mTOR) signaling pathway was activated to enhance the translation of Fc-fusion protein, and the block in post-translational steps of Fc-fusion protein was alleviated by YE addition as well. Our results revealed the responses of multiple protein production steps to the addition of YE and provided a practical guidance for the separation and application of active compounds from hydrolysates. PMID:26162671

  15. GeneOptimizer program-assisted cDNA reengineering enhances sRAGE autologous expression in Chinese hamster ovary cells.

    Science.gov (United States)

    Wei, Wen; Kim, Ji Min; Medina, Danny; Lakatta, Edward G; Lin, Li

    2014-03-01

    Soluble receptor for advanced glycation end products (sRAGE) is a secreted mammalian protein that functions as a decoy to counter-react RAGE signaling-resultant pathological conditions, and has high therapeutic potentials. Our prior studies showed that recombinant human sRAGE expressed in Chinese hamster, Ceanothus griseus, ovary (CHO) cells is modified by specific N-glycosylation, and exhibits higher bioactivity than that expressed in other host systems including insect Spodoptera frugiperda cells. Here, we show that GeneOptimizer software program-assisted, reengineered sRAGE cDNA enhances the recombinant protein expression in CHO cells. The cDNA sequence encoding human sRAGE was optimized for RNA structure, stability, and codon usages in CHO cells. We found that such optimization augmented sRAGE expression over 2 folds of its wild-type counterpart. We also studied how individual parameter impacted sRAGE autologous expression in CHO cells, and whether sRAGE bioactivity was compromised. We found that the enhanced expression appeared not to affect sRAGE N-glycosylation and bioactivity. Optimization of sRAGE expression provides a basis for future large-scale production of this protein to meet medical needs. PMID:24373844

  16. Transfection of Chinese hamster ovary DHFR/sup -/ cells with the gene coding for heat shock protein 70 from drosophila melanogaster

    International Nuclear Information System (INIS)

    Chinese hamster ovary DHFR/sup -/ cells (CHO-DHFR/sup -/) were transfected with the plasmid pSV2-dhfr expressing the mouse gene coding for dhfr or with the same plasmid containing the gene coding for the Drosophila melanogaster heat shock protein 70 (hsp70), pSVd-hsp70. Three subcloned cell lines selected for expression of the dhfr gene were shown to contain either the vector sequence (G cells) or varying copies of pSVd-hsp70 (H cells). One line of H cells was shown to contain > 30 copies of the D. melanogaster hsp70 gene and to express the hsp70 RNA at significant levels. No difference between G and H cells was observed in the rate of growth, in the development of thermotolerance, or in the sensitivity of actin microfilament bundles to heat shock. However, H cells containing the transfected hsp70 gene had an altered morphology when compared to the G cells and the parental CHO-DHFR/sup -/ cells being more fibroblastic. The adhesion properties of the H cells was also decreased when compared to the G cells. These results show that insertion of the D. melanogaster gene into CHO cells does not effect growth rates or heat shock responses but may alter cell morphology and adhesion

  17. The zinc ionophore clioquinol reverses autophagy arrest in chloroquine-treated ARPE-19 cells and in APP/mutant presenilin-1-transfected Chinese hamster ovary cells.

    Science.gov (United States)

    Seo, Bo-Ra; Lee, Sook-Jeong; Cho, Kyung Sook; Yoon, Young Hee; Koh, Jae-Young

    2015-12-01

    Arrested autophagy may contribute to the pathogenesis of Alzheimer's disease. Because we found that chloroquine (CQ) causes arrested autophagy but clioquinol (ClioQ), a zinc ionophore, activates autophagic flux, in the present study, we examined whether ClioQ can overcome arrested autophagy induced by CQ or mutant presenilin-1 (mPS1). CQ induced vacuole formation and cell death in adult retinal pigment epithelial (ARPE-19) cells, but co-treatment with ClioQ attenuated CQ-associated toxicity in a zinc-dependent manner. Increases in lysosome dilation and blockage of autophagic flux by CQ were also markedly attenuated by ClioQ treatment. Interestingly, CQ increased lysosomal pH in amyloid precursor protein (APP)/mPS1-expressing Chinese hamster ovary 7WΔE9 (CHO-7WΔE9) cell line, and ClioQ partially re-acidified lysosomes. Furthermore, accumulation of amyloid-β (Aβ) oligomers in CHO-7WΔE9 cells was markedly attenuated by ClioQ. Moreover, intracellular accumulation of exogenously applied fluorescein isothiocyanate-conjugated Aβ(1-42) was also increased by CQ but was returned to control levels by ClioQ. These results suggest that modulation of lysosomal functions by manipulating lysosomal zinc levels may be a useful strategy for clearing intracellular Aβ oligomers. PMID:26453000

  18. Sustained productivity in recombinant Chinese Hamster Ovary (CHO cell lines: proteome analysis of the molecular basis for a process-related phenotype

    Directory of Open Access Journals (Sweden)

    Gammell Patrick

    2011-07-01

    Full Text Available Abstract Background The ability of mammalian cell lines to sustain cell specific productivity (Qp over the full duration of bioprocess culture is a highly desirable phenotype, but the molecular basis for sustainable productivity has not been previously investigated in detail. In order to identify proteins that may be associated with a sustained productivity phenotype, we have conducted a proteomic profiling analysis of two matched pairs of monoclonal antibody-producing Chinese hamster ovary (CHO cell lines that differ in their ability to sustain productivity over a 10 day fed-batch culture. Results Proteomic profiling of inherent differences between the two sets of comparators using 2D-DIGE (Difference Gel Electrophoresis and LC-MS/MS resulted in the identification of 89 distinct differentially expressed proteins. Overlap comparisons between the two sets of cell line pairs identified 12 proteins (AKRIB8, ANXA1, ANXA4, EIF3I, G6PD, HSPA8, HSP90B1, HSPD1, NUDC, PGAM1, RUVBL1 and CNN3 that were differentially expressed in the same direction. Conclusion These proteins may have an important role in sustaining high productivity of recombinant protein over the duration of a fed-batch bioprocess culture. It is possible that many of these proteins could be useful for future approaches to successfully manipulate or engineer CHO cells in order to sustain productivity of recombinant protein.

  19. Chromium(VI)-induced Production of Reactive Oxygen Species, Change of Plasma Membrane Potential and Dissipation of Mitochondria Membrane Potential in Chinese Hamster Lung Cell Cultures

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective To examine whether Reactive Oxygen Species (ROS) is generated, and whether plasma membrane potential and mitochondrial membrane potential are depolarized in Chinese Hamster Lung (CHL) cell lines exposed to Cr (VI). Methods CHL cells were incubated with Cr(VI) at 10 μmol/L, 2.5 μmol/L, 0.65 μmol/L for 3 and 6 hours, respectively. The production of ROS was performed by using 2,7_dichlorofluorescin diacetate; The changes in plasma membrane potential were estimated using fluorescent cationic dye DiBAC4; And the changes in mitochondria membrane potential were estimated using fluorescent dye Rhodamine 123. Results The ROS levels in CHL cells increased in all treated groups compared with the control group (P<0.01); The plasma membrane potential and mitochondrial membrane potential in CHL cells dissipated after incubated with Cr(VI) at 10 μmol/L for 3 hours and 6 hours (P<0.01), at 2.5 μmol/L for 6 hours (P<0.01 or 0.05). Conclusion Cr(VI) causes the dissipation of plasma membrane potential and mitochondrial membrane potential in CHL cell cultures, and Cr(VI)_induced ROS may play a role in the injuries.

  20. Chromium(VI)—induces Production of Reactive Oxygen Species,Change of Plasma Membrane Potential and Dissipation of Mitochondria Membrane otential in Chinese Hamster Lung Cell Cultures

    Institute of Scientific and Technical Information of China (English)

    XIEYI; ZHUANGZHI-XIONG

    2001-01-01

    Objective:To examine whether Reactive Oxygen Species(ROS) is generated,and whether plasma membrane potential and mitochnodrial membrane potential are depolarized in Chinese Hamster Lung(CHL)cell lines exposed to Cr(VI),Methods:CHL Cells were incubated with Cr(VI) at 10 umol/L,2.5umol/L,0.65umol/L for 3 and 6 hours,respectively.The rpoduction of ROS was performed by using 2,7-dichlorofluorescin discetate;The changes in plasma membrane potential were performed by using 2,7-dichlorofluorescin discetate;The changes in plasma membrane potential were performed by using 2,7-dichlorofluorescin diacetate;The changes in plasma membrane potential were estimated using fluorescent cationic dye DiBAC4;And the changes in mitochondria membrane potential were estimated using fluorescent dye Rhodamine 123,Results:The ROS levels in CHL cells increased in all treated groups compared with the control group(P<0.01);The plasma membrane potential and mitochondrial membrane potential in CHL cells dissipated after incubated with Cr(VI) at 10umol/L for 3 hours and 6 hours(P<0.01),at 2.5umol/L for 6 hours(P<0.01 or 0.05),Conclusion:Cr(VI) causes the dissipation of plasma membrane potential and mitochnodrial membrane otential in CHL cell cultrues,and Cr(VI)-induced ROS may play a role in the injuries.

  1. The effects of captan and captafol on different bacterial strains and on c-mitosis in V79 Chinese hamster fibroblasts.

    Science.gov (United States)

    Rahden-Staroń, I; Szumiło, M; Ziemkiewicz, P

    1994-01-01

    The mutagenic activity of captan and captafol was tested using Ames strains and strains showing an SOS response. Captafol was mutagenic in S. typhimurium strain TA102 (uvr+) and captan in strain TA104 (uvrB). Both captan and captafol elicit damages in DNA recognized by correndonuclease II, as shown by the repair test, and induced the SOS repair system in E. coli PQ37 (uvrA) strain. Only captafol induced the SOS system in PQ35 (uvr+). The lack of induction of beta-galactosidase at nonpermissive temperature in E. coli MD332 (dnaCs uvrA) strain showed that neither chemical was able to produce DNA breaks. In V79 Chinese hamster fibroblasts higher induction of c-mitosis by captafol than by captan (22% and 15% over the control, respectively) was accompanied by a higher decrease in nonprotein sulfhydryl groups, mainly GSH (41% and 77%, respectively). The content of protein sulfhydryl groups was decreased by either fungicide to a similar extent.

  2. Comparative study of the cytotoxic and genotoxic effects of titanium oxide and aluminium oxide nanoparticles in Chinese hamster ovary (CHO-K1) cells

    International Nuclear Information System (INIS)

    The aim of this study was to analyze the cytotoxicity and genotoxicity of titanium oxide (TiO2) and aluminium oxide (Al2O3) nanoparticles (NPs) on Chinese hamster ovary (CHO-K1) cells using neutral red (NR), mitochondrial activity (by MTT assay), sister chromatid exchange (SCE), micronucleus (MN) formation, and cell cycle kinetics techniques. Results showed a dose-related cytotoxic effect evidenced after 24 h by changes in lysosomal and mitochondrial dehydrogenase activity. Interestingly, transmission electronic microscopy (TEM) showed the formation of perinuclear vesicles in CHO-K1 cells after treatment with both NPs during 24 h but no NP was detected in the nuclei. Genotoxic effects were shown by MN frequencies which significantly increased at 0.5 and 1 μg/mL TiO2 and 0.5-10 μg/mL Al2O3. SCE frequencies were higher for cells treated with 1-5 μg/mL TiO2. The absence of metaphases evidenced cytotoxicity for higher concentrations of TiO2. No SCE induction was achieved after treatment with 1-25 μg/mL Al2O3. In conclusion, findings showed cytotoxic and genotoxic effects of TiO2 and Al2O3 NPs on CHO-K1 cells. Possible causes of controversial reports are discussed further on.

  3. Sustained productivity in recombinant Chinese Hamster Ovary (CHO) cell lines: proteome analysis of the molecular basis for a process-related phenotype

    LENUS (Irish Health Repository)

    Meleady, Paula

    2011-07-24

    Abstract Background The ability of mammalian cell lines to sustain cell specific productivity (Qp) over the full duration of bioprocess culture is a highly desirable phenotype, but the molecular basis for sustainable productivity has not been previously investigated in detail. In order to identify proteins that may be associated with a sustained productivity phenotype, we have conducted a proteomic profiling analysis of two matched pairs of monoclonal antibody-producing Chinese hamster ovary (CHO) cell lines that differ in their ability to sustain productivity over a 10 day fed-batch culture. Results Proteomic profiling of inherent differences between the two sets of comparators using 2D-DIGE (Difference Gel Electrophoresis) and LC-MS\\/MS resulted in the identification of 89 distinct differentially expressed proteins. Overlap comparisons between the two sets of cell line pairs identified 12 proteins (AKRIB8, ANXA1, ANXA4, EIF3I, G6PD, HSPA8, HSP90B1, HSPD1, NUDC, PGAM1, RUVBL1 and CNN3) that were differentially expressed in the same direction. Conclusion These proteins may have an important role in sustaining high productivity of recombinant protein over the duration of a fed-batch bioprocess culture. It is possible that many of these proteins could be useful for future approaches to successfully manipulate or engineer CHO cells in order to sustain productivity of recombinant protein.

  4. Cytogenetic response to 1,2-dicarbonyls and hydrogen peroxide in Chinese hamster ovary AUXB1 cells and human peripheral lymphocytes.

    Science.gov (United States)

    Tucker, J D; Taylor, R T; Christensen, M L; Strout, C L; Hanna, M L; Carrano, A V

    1989-10-01

    Mutagenic 1,2-dicarbonyls have been reported to occur in coffee and other beverages and in various foods. We have measured the induction of sister-chromatid exchanges (SCEs) and endoreduplicated cells (ERCs) to determine the genotoxicity of various 1,2-dicarbonyl compounds in Chinese hamster ovary (CHO) AUXB1 cells and human peripheral lymphocytes. The 1,2-dicarbonyls glyoxal, methylglyoxal and kethoxal each induced highly significant increases in both SCEs and ERCs in AUXB1 cells. Glyoxal and kethoxal induced SCEs but not ERCs in human peripheral lymphocytes. In addition, hydrogen peroxide induced highly significant levels of SCEs and ERCs in AUXB1 cells. Bisulfite, which reacts with carbonyl groups to form addition products, significantly reduced the frequency of SCEs and the proportion of ERCs when glyoxal, methylglyoxal, kethoxal and diacetyl were administered to AUXB1 cells. In addition, bisulfite blocked the formation of ERCs, but not SCEs, induced by hydrogen peroxide. These in vitro results suggest that 1,2-dicarbonyls may play an important role in the genotoxicity of some foods and beverages.

  5. Monitoring utilizations of amino acids and vitamins in culture media and Chinese hamster ovary cells by liquid chromatography tandem mass spectrometry.

    Science.gov (United States)

    Qiu, Jinshu; Chan, Pik Kay; Bondarenko, Pavel V

    2016-01-01

    Monitoring amino acids and vitamins is important for understanding human health, food nutrition and the culture of mammalian cells used to produce therapeutic proteins in biotechnology. A method including ion pairing reversed-phase liquid chromatography with tandem mass spectrometry was developed and optimized to quantify 21 amino acids and 9 water-soluble vitamins in Chinese hamster ovary (CHO) cells and culture media. By optimizing the chromatographic separation, scan time, monitoring time window, and sample preparation procedure, and using isotopically labeled (13)C, (15)N and (2)H internal standards, low limits of quantitation (≤0.054 mg/L), good precision (amino acids showed a zigzag pattern with maxima at the feeding days, and 9 non-essential amino acids displayed a smoothly changing profile as they were mainly products of cellular metabolism. Five of 9 vitamins accumulated continuously during the culture period, suggesting that they were fed in access. The method serves as an effective tool for the development and optimization of mammalian cell cultures.

  6. Differential toxicity of mitomycin C and porfiromycin to aerobic and hypoxic Chinese hamster ovary cells overexpressing human NADPH:cytochrome c (P-450) reductase.

    Science.gov (United States)

    Belcourt, M F; Hodnick, W F; Rockwell, S; Sartorelli, A C

    1996-01-01

    Purified NADPH:cytochrome c (P-450) reductase (FpT; NADPH-ferrihemoprotein oxidoreductase, EC 1.6.2.4) can reductively activate mitomycin antibiotics through a one-electron reduction to species that alkylate DNA. To assess the involvement of FpT in the intracellular activation of the mitomycins, transfectants overexpressing a human FpT cDNA were established from a Chinese hamster ovary cell line deficient in dihydrofolate reductase (CHO-K1/dhfr-). The parental cell line was equisensitive to the cytotoxic action of mitomycin C under oxygenated and hypoxic conditions. In contrast, porfiromycin was considerably less cytotoxic to wild-type parental cells than was mitomycin C in air and markedly more cytotoxic under hypoxia. Two FpT-transfected clones were selected that expressed 19- and 27-fold more FpT activity than the parental line. Levels of other oxidoreductases implicated in the activation of the mitomycins were unchanged. Significant increases in sensitivity to mitomycin C and porfiromycin in the two FpT-transfected clones were seen under both oxygenated and hypoxic conditions, with the increases in toxicity being greater under hypoxia than in air. These findings demonstrate that FpT can bioreductively activate the mitomycins in living cells and implicate FpT in the differential aerobic/hypoxic toxicity of the mitomycins. PMID:8552660

  7. The intracellular location of NADH:cytochrome b5 reductase modulates the cytotoxicity of the mitomycins to Chinese hamster ovary cells.

    Science.gov (United States)

    Belcourt, M F; Hodnick, W F; Rockwell, S; Sartorelli, A C

    1998-04-10

    NADH:cytochrome b5 reductase activates the mitomycins to alkylating intermediates in vitro. To investigate the intracellular role of this enzyme in mitomycin bioactivation, Chinese hamster ovary cell transfectants overexpressing rat NADH:cytochrome b5 reductase were generated. An NADH:cytochrome b5 reductase-transfected clone expressed 9-fold more enzyme than did parental cells; the levels of other mitomycin-activating oxidoreductases were unchanged. Although this enzyme activates the mitomycins in vitro, its overexpression in living cells caused decreases in sensitivity to mitomycin C in air and decreases in sensitivity to porfiromycin under both air and hypoxia. Mitomycin C cytotoxicity under hypoxia was similar to parental cells. Because NADH:cytochrome b5 reductase resides predominantly in the mitochondria of these cells, this enzyme may sequester these drugs in this compartment, thereby decreasing nuclear DNA alkylations and reducing cytotoxicity. A cytosolic form of NADH:cytochrome b5 reductase was generated. Transfectants expressing the cytosolic enzyme were restored to parental line sensitivity to both mitomycin C and porfiromycin in air with marked increases in drug sensitivity under hypoxia. The results implicate NADH:cytochrome b5 reductase in the differential bioactivation of the mitomycins and indicate that the subcellular site of drug activation can have complex effects on drug cytotoxicity. PMID:9535868

  8. A simple and reliable in vitro test system for the analysis of induced aneuploidy as well as other cytogenetic end-points using Chinese hamster cells

    International Nuclear Information System (INIS)

    Although aneuploidy is a serious human health problem, the experimental methodology devised until now to study the mechanisms involved in the induction of aneuploidy and for the screening of aneuploidy-inducing agents has not been so much employed to have the necessary validation. A procedure using primary cell cultures of Chinese hamster embryo cells grown on cover glasses is described. To avoid the excessive scattering and subsequent loss of chromosomes, a hypotonic treatment with a 0.17% sodium chloride solution, at room temperature, followed by in situ fixation has been standardized. This procedure improves the method through the reduction of the spontaneous frequency of aneuploid cells. Experiments carried out with cells treated with X-rays, X-rays plus caffeine, and the synthetic estrogen diethylstilbestrol (DES) demonstrated the accuracy of the system since the average chromosome number remained constant in spite of the induction of high frequencies of aneuploid cells. Moreover, the method allows for the analysis of other cytogenetic endpoints such as anaphase-telophase alterations, structural chromosome aberrations or sister chromatid exchanges. (author)

  9. Moral Disengagement Among Bystanders to School Bullying

    DEFF Research Database (Denmark)

    Obermann, Marie-Louise

    2011-01-01

    This study examined the use of moral disengagement among children indirectly involved in bullying (bystanders). A sample of Danish adolescents (N = 660, M age 12.6 years) were divided into four groups depending on their bystander status: (a) outsiders, who did not experience bullying among...... their peers; (b) defenders, who were likely to help the victims in bullying episodes; (c) guilty bystanders, who did nothing to help bullied peers but felt guilty about it; and (d) unconcerned bystanders, who witnessed peers being bullied, without feeling responsible. Results indicated that, besides from...... active personal involvement in bullying others, being an unconcerned bystander to bullying also associates with moral disengagement. Unconcerned bystanders had significantly higher moral disengagement than guilty bystanders and defenders. Outsiders also showed significant higher disengagement than...

  10. Hyper-radiosensitivity and induced radioresistance and bystander effects in rodent and human cells as a function of radiation quality

    International Nuclear Information System (INIS)

    In the past two decades, a body of experimental evidences in vitro has shown the presence of a plethora of phenomena occurring after low-dose irradiation [including hypersensitivity and induced radioresistance (IRR), adaptive response, bystander effect (BE) and genomic instability], which might imply a non-linear behaviour of cancer risk curves in the low-dose region and question the validity of the linear no-threshold model for cancer risk assessment in such a dose region. In this framework, a systematic investigation have been undertaken on non-linear effects at low doses as a function of different radiation quality and cellular radiosensitivity and in terms of different biological end points. The present article reports the recent results on hyper-radiosensitivity and IRR and BE phenomena, in terms of clonogenic survival in V79 Chinese hamster cells and T98G human glioblastoma cells irradiated with protons and carbon ions with different energy, as a function of dose (and fluence). (authors)

  11. Comparative study of the cytotoxic and genotoxic effects of titanium oxide and aluminium oxide nanoparticles in Chinese hamster ovary (CHO-K1) cells

    Energy Technology Data Exchange (ETDEWEB)

    Di Virgilio, A.L. [Instituto de Investigaciones Fisicoquimicas Teoricas y Aplicadas (INIFTA), Diag. 113 y 64, Correo 16, Suc. 4, La Plata (1900) (Argentina); Reigosa, M. [Instituto Multidisciplinario de Biologia Celular (IMBICE), Calle 526 y Camino Gral. Belgrano (entre 10 y 11), La Plata 1900 (Argentina); Arnal, P.M. [Instituto de Investigaciones Fisicoquimicas Teoricas y Aplicadas (INIFTA), Diag. 113 y 64, Correo 16, Suc. 4, La Plata 1900 (Argentina); Fernandez Lorenzo de Mele, M., E-mail: mmele@inifta.unlp.edu.ar [Instituto de Investigaciones Fisicoquimicas Teoricas y Aplicadas (INIFTA), Diag. 113 y 64, Correo 16, Suc. 4, La Plata 1900 (Argentina)

    2010-05-15

    The aim of this study was to analyze the cytotoxicity and genotoxicity of titanium oxide (TiO{sub 2}) and aluminium oxide (Al{sub 2}O{sub 3}) nanoparticles (NPs) on Chinese hamster ovary (CHO-K1) cells using neutral red (NR), mitochondrial activity (by MTT assay), sister chromatid exchange (SCE), micronucleus (MN) formation, and cell cycle kinetics techniques. Results showed a dose-related cytotoxic effect evidenced after 24 h by changes in lysosomal and mitochondrial dehydrogenase activity. Interestingly, transmission electronic microscopy (TEM) showed the formation of perinuclear vesicles in CHO-K1 cells after treatment with both NPs during 24 h but no NP was detected in the nuclei. Genotoxic effects were shown by MN frequencies which significantly increased at 0.5 and 1 {mu}g/mL TiO{sub 2} and 0.5-10 {mu}g/mL Al{sub 2}O{sub 3}. SCE frequencies were higher for cells treated with 1-5 {mu}g/mL TiO{sub 2}. The absence of metaphases evidenced cytotoxicity for higher concentrations of TiO{sub 2}. No SCE induction was achieved after treatment with 1-25 {mu}g/mL Al{sub 2}O{sub 3}. In conclusion, findings showed cytotoxic and genotoxic effects of TiO{sub 2} and Al{sub 2}O{sub 3} NPs on CHO-K1 cells. Possible causes of controversial reports are discussed further on.

  12. Predicting the expression of recombinant monoclonal antibodies in Chinese hamster ovary cells based on sequence features of the CDR3 domain.

    Science.gov (United States)

    Pybus, Leon P; James, David C; Dean, Greg; Slidel, Tim; Hardman, Colin; Smith, Andrew; Daramola, Olalekan; Field, Ray

    2014-01-01

    Despite the development of high-titer bioprocesses capable of producing >10 g L(-1) of recombinant monoclonal antibody (MAb), some so called "difficult-to-express" (DTE) MAbs only reach much lower process titers. For widely utilized "platform" processes the only discrete variable is the protein coding sequence of the recombinant product. However, there has been little systematic study to identify the sequence parameters that affect expression. This information is vital, as it would allow us to rationally design genetic sequence and engineering strategies for optimal bioprocessing. We have therefore developed a new computational tool that enables prediction of MAb titer in Chinese hamster ovary (CHO) cells based on the recombinant coding sequence of the expressed MAb. Model construction utilized a panel of MAbs, which following a 10-day fed-batch transient production process varied in titer 5.6-fold, allowing analysis of the sequence features that impact expression over a range of high and low MAb productivity. The model identified 18 light chain (LC)-specific sequence features within complementarity determining region 3 (CDR3) capable of predicting MAb titer with a root mean square error of 0.585 relative expression units. Furthermore, we identify that CDR3 variation influences the rate of LC-HC dimerization during MAb synthesis, which could be exploited to improve the production of DTE MAb variants via increasing the transfected LC:HC gene ratio. Taken together these data suggest that engineering intervention strategies to improve the expression of DTE recombinant products can be rationally implemented based on an identification of the sequence motifs that render a recombinant product DTE.

  13. Changes in the Number of Double-Strand DNA Breaks in Chinese Hamster V79 Cells Exposed to γ-Radiation with Different Dose Rates

    Directory of Open Access Journals (Sweden)

    Andreyan N. Osipov

    2013-07-01

    Full Text Available A comparative investigation of the induction of double-strand DNA breaks (DSBs in the Chinese hamster V79 cells by γ-radiation at dose rates of 1, 10 and 400 mGy/min (doses ranged from 0.36 to 4.32 Gy was performed. The acute radiation exposure at a dose rate of 400 mGy/min resulted in the linear dose-dependent increase of the γ-H2AX foci formation. The dose-response curve for the acute exposure was well described by a linear function y = 1.22 + 19.7x, where “y” is an average number of γ-H2AX foci per a cell and “x” is the absorbed dose (Gy. The dose rate reduction down to 10 mGy/min lead to a decreased number of γ-H2AX foci, as well as to a change of the dose-response relationship. Thus, the foci number up to 1.44 Gy increased and reached the “plateau” area between 1.44 and 4.32 Gy. There was only a slight increase of the γ-H2AX foci number (up to 7 in cells after the protracted exposure (up to 72 h to ionizing radiation at a dose rate of 1 mGy/min. Similar effects of the varying dose rates were obtained when DNA damage was assessed using the comet assay. In general, our results show that the reduction of the radiation dose rate resulted in a significant decrease of DSBs per cell per an absorbed dose.

  14. Multiplex polymerase chain reaction analysis of UV-A- and UV-B-induced delayed and early mutations in V79 Chinese hamster cells.

    Science.gov (United States)

    Dahle, Jostein; Noordhuis, Paul; Stokke, Trond; Svendsrud, Debbie Hege; Kvam, Egil

    2005-01-01

    We previously reported that approximately 10% of V79 Chinese hamster fibroblast populations clonally derived from single cells immediately after irradiation with either ultraviolet B (UV-B, 290-320 nm, mainly 311 nm) or ultraviolet A (UV-A, 320-400 nm, mainly 350-390 nm) radiation exhibit genomic instability. The instability is revealed by relatively high mutation frequencies in the hypoxanthine phosphoribosyl transferase (hprt) gene up to 23 cell generations after irradiation. These delayed mutant clones exhibited higher levels of oxidative stress than normal cells. Therefore, persistently increased oxidative stress has been proposed as a mechanism for UV-induced genomic instability. This study investigates whether this mechanism is reflected in the deletion spectrum of delayed mutant clones. Eighty-eight percent of the delayed mutant clones derived from UV-A-irradiated populations were found to have total deletion of the hprt gene. Correspondingly, 81% of UV-A-induced early mutations (i.e. detected shortly after irradiation) also had total deletions. Among delayed UV-B-induced mutant clones, 23% had total deletions and 8% had deletion of one exon, whereas all early UV-B events were either point mutations or small deletions or insertions. In conclusion, the multiplex polymerase chain reaction deletion screen showed that there were explicit differences in the occurrence of large gene alterations between early and delayed mutations induced by UV-B radiation. For UV-A radiation the deletion spectra were similar for delayed and early mutations. UV-A radiation is, in contrast to UV-B radiation, only weakly absorbed by DNA and probably induces mutation almost solely via production of reactive oxygen species. Therefore, the present results support the hypothesis that persistent increase in oxidative stress is involved in the mechanism of UV-induced genomic instability.

  15. Inhibition of serine palmitoyltransferase in vitro and long-chain base biosynthesis in intact Chinese hamster ovary cells by. beta. -chloroalanine

    Energy Technology Data Exchange (ETDEWEB)

    Medlock, K.A.; Merrill, A.H. Jr.

    1988-09-06

    The effects of ..beta..-chloroalanine (..beta..-Cl-alanine) on the serine palmitoyltransferase activity and the de novo biosynthesis of sphinganine and sphingenine were investigated in vitro with rat liver microsomes and in vivo with intact Chinese hamster ovary (CHO) cells. The inhibition in vitro was rapid, irreversible, and concentration and time dependent and apparently involved the active site because inactivation only occurred with ..beta..-Cl-L-alanine and was blocked by L-serine. These are characteristics of mechanism-based (suicide) inhibition. Serine palmitoyltransferase (SPT) was also inhibited when intact CHO cells were incubated with ..beta..-Cl-alanine and this treatment inhibited (/sup 14/C)serine incorporation into long-chain bases by intact cells. The concentration dependence of the loss of SPT activity and of long-chain base synthesis was identical. The effects of ..beta..-Cl-alanine appeared to occur with little perturbation of other cell functions: the cells exhibited no loss in cell viability, (/sup 14/C)serine uptake was not blocked, total lipid biosynthesis from (/sup 14/C)acetic acid was not decreased (nor was the appearance of radiolabel in cholesterol and phosphatidylcholine), and (/sup 3/H)thymidine incorporation into DNA was not affected. There appeared to be little effect on protein synthesis based on the incorporation of (/sup 3/H)leucine, which was only decreased by 14%. Although ..beta..-Cl-L-alanine is known to inhibit other pyridoxal 5'-phosphate dependent enzymes, alanine and aspartate transaminases were not inhibited under these conditions. These results establish the close association between the activity of serine palmitoyltransferase and the cellular rate of long-chain base formation and indicate that ..beta..-Cl-alanine and other mechanism-based inhibitors might be useful to study alterations in cellular long-chain base synthesis.

  16. Purification and characterization of chimeric human IgA1 and IgA2 expressed in COS and Chinese hamster ovary cells.

    Science.gov (United States)

    Morton, H C; Atkin, J D; Owens, R J; Woof, J M

    1993-11-01

    Ag-specific chimeric human IgA molecules, of the two human subclasses, IgA1 and IgA2, have been expressed in two mammalian cell systems. Analysis of the secreted IgA molecules, purified in milligram quantities from stable Chinese hamster ovary transfectants by Ag affinity chromatography, has allowed a direct comparison of the biologic properties of the two subclasses. HPLC gel filtration analysis revealed that in both subclasses, the IgA molecules associate predominantly into dimers. The monomer units are presumed to interact noncovalently, inasmuch as no dimers are evident when the antibodies are subjected to SDS-PAGE. The recombinant antibodies are glycosylated, inasmuch as a lectin blotting procedure revealed that the H chains of both subclasses are recognized by Con A. When subjected to digestion by preparations of IgA1-specific proteases secreted by two pathogenic streptococcal strains, Streptococcus sanguis and Streptococcus oralis, the recombinant IgA molecules behave just as their natural equivalents. Thus, only the chimeric IgA1 molecule is cleaved, with the IgA2 remaining intact. In terms of interaction with natural effector molecules, both recombinant IgA isotypes were shown to interact with Fc alpha receptors on calcitriol-stimulated HL-60 cells with similar affinity, but neither antibody was found to interact with human C1q. The expression system described readily permits manipulation of the human IgA genes, which should lead to a fuller molecular understanding of how this important antibody mediates its function. PMID:8409433

  17. Down-regulation of cold-inducible RNA-binding protein does not improve hypothermic growth of Chinese hamster ovary cells producing erythropoietin.

    Science.gov (United States)

    Hong, Jong Kwang; Kim, Yeon-Gu; Yoon, Sung Kwan; Lee, Gyun Min

    2007-03-01

    Discovery of the cold-inducible RNA-binding protein (CIRP) in mouse fibroblasts suggests that growth suppression at hypothermic conditions is due to an active response by the cell rather than due to passive thermal effects. To determine the effect of down-regulated CIRP expression on cell growth and erythropoietin (EPO) production in recombinant Chinese hamster ovary (rCHO) cells at low culture temperature, stable CHO cell clones with reduced CIRP expression level were established by transfecting (rCHO) cells with the CIRP siRNA vector with a target sequence of TCGTCCTTCCATGGCTGTA. For comparison of the degree of specific growth rate (micro) reduction at low culture temperature, three CIRP-reduced clones with different mu and three control clones transfected with null vector were cultivated at two different temperatures, 32 degrees C and 37 degrees C. Unlike mouse fibroblasts, alleviation of hypothermic growth arrest of rCHO cells by CIRP down-regulation was insignificant, as shown by statistical analysis using the t-test (P<0.18, n=3). The ratios of mu at 32 degrees C to micro at 37 degrees C of CIRP-reduced clones and control clones were 0.29+/-0.03 and 0.25+/-0.03 on an average, respectively. Furthermore, it was also found that overexpression of CIRP did not inhibit rCHO cell growth significantly at 37 degrees C. Taken together, the data obtained show that down-regulation of only CIRP in rCHO cells, unlike mouse fibroblasts, is not sufficient to recover growth arrest at low-temperature culture (32 degrees C). PMID:17239640

  18. Molecular polygamy: The promiscuity of l-phenylalanyl-tRNA-synthetase triggers misincorporation of meta- and ortho-tyrosine in monoclonal antibodies expressed by Chinese hamster ovary cells.

    Science.gov (United States)

    Popp, Oliver; Larraillet, Vincent; Kettenberger, Hubert; Gorr, Ingo H; Hilger, Maximiliane; Lipsmeier, Florian; Zeck, Anne; Beaucamp, Nicola

    2015-06-01

    In-depth analytical characterization of biotherapeutics originating from different production batches is mandatory to ensure product safety and consistent molecule efficacy. Previously, we have shown unintended incorporation of tyrosine (Tyr) and leucine/isoleucine (Leu/Ile) at phenylalanine (Phe) positions in a recombinant produced monoclonal antibody (mAb) using an orthogonal MASCOT/SIEVE based approach for mass spectrometry data analysis. The misincorporation could be avoided by sufficient supply of phenylalanine throughout the process. Several non-annotated signals in the primarily chromatographic peptide separation step for apparently single Phe→Tyr sequence variants (SVs) suggest a role for isobar tyrosine isoforms. Meta- and ortho-Tyr are spontaneously generated during aerobic fed-batch production processes using Chinese hamster ovary (CHO) cell lines. Process induced meta- and ortho-Tyr but not proteinogenic para-Tyr are incorporated at Phe locations in Phe-starved CHO cultures expressing a recombinant mAb. Furthermore, meta- and ortho-Tyr are preferably misincorporated over Leu. Structural modeling of the l-phenylalanyl-tRNA-synthetase (PheRS) substrate activation site indicates a possible fit of non-cognate ortho-Tyr and meta-Tyr substrates. Dose-dependent misincorporations of Tyr isoforms support the hypothesis that meta- and ortho-Tyr are competing, alternative substrates for PheRS in CHO processes. Finally, easily accessible at-line surrogate markers for Phe→Tyr SV formation in biotherapeutic production were defined by the calculation of critical ratios for meta-Tyr/Phe and ortho-Tyr/Phe to support early prediction of SV probability, and finally, to allow for immediate process controlled Phe→Tyr SV prevention.

  19. Cell killing, nuclear damage and apoptosis in Chinese hamster V79 cells after irradiation with heavy-ion beams of (16)O, (12)C and (7)Li.

    Science.gov (United States)

    Pathak, Rupak; Dey, Subrata Kumar; Sarma, Asiti; Khuda-Bukhsh, Anisur Rahman

    2007-08-15

    Chinese hamster V79 cells were exposed to high LET (linear energy transfer) (16)O-beam (625keV/mum) radiation in the dose range of 0-9.83Gy. Cell survival, micronuclei (MN), chromosomal aberrations (CA) and induction of apoptosis were studied as a follow up of our earlier study on high LET radiations ((7)Li-beam of 60keV/mum and (12)C-beam of 295keV/mum) as well as (60)Co gamma-rays. Dose dependent decline in surviving fraction was noticed along with the increase of MN frequency, CA frequency as well as percentage of apoptosis as detected by nuclear fragmentation assay. The relative intensity of DNA ladder, which is a useful marker for the determination of the extent of apoptosis induction, was also increased in a dose dependent manner. Additionally, expression of tyrosine kinase lck-1 gene, which plays an important role in response to ionizing radiation induced apoptosis, was increased with the increase of radiation doses and also with incubation time. The present study showed that all the high LET radiations were generally more effective in cell killing and inflicting other cytogenetic damages than that of low LET gamma-rays. The dose response curves revealed that (7)Li-beam was most effective in cell killing as well as inducing other nuclear damages followed by (12)C, (16)O and (60)Co gamma-rays, in that order. The result of this study may have some application in biological dosimetry for assessment of genotoxicity in heavy ion exposed subjects and in determining suitable doses for radiotherapy in cancer patients where various species of heavy ions are now being generally used.

  20. Follicle-stimulating Hormone (FSH) Induced Internalization of Porcine FSH Receptor in Cultured Porcine Granulosa Cells and Chinese Hamster Ovary Cells Transfected with Recombinant Porcine FSH Receptor cDNA

    Institute of Scientific and Technical Information of China (English)

    ZHU Changhong; TIAN Hong; XIONG Zhongming; XIA Huizhu

    2001-01-01

    In order to study the fate of human follicle-stimulating hormone (FSH) when hormone binds to its receptor, a quick biochemical method that can differentiate between the surface-bound and internalized hormone was used to determine the internalization induced by FSH in cultured both porcine granulosa cells and Chinese hamster ovary (CHO) cells expressing recombinant porcine FSH receptor. The results showed that FSH was slowly internalized, and the internalized radioactivity (acid resistant) reached a peak 10-12 h after addition of 125I-hFSH. It was suggested that FSHR do not get internalized rapidly under physiological circumstances precisely because the appropriate sequences are absent.

  1. Evidence for cross-talk between M2 and M3 muscarinic acetylcholine receptors in the regulation of second messenger and extracellular signal-regulated kinase signalling pathways in Chinese hamster ovary cells

    OpenAIRE

    Hornigold, David C; Mistry, Rajendra; Raymond, Pamela D; Blank, Jonathan L; John Challiss, R A

    2003-01-01

    We have examined possible mechanisms of cross-talk between the Gq/11-linked M3 muscarinic acetylcholine (mACh) receptor and the Gi/o-linked M2 mACh receptor by stable receptor coexpression in Chinese hamster ovary (CHO) cells. A number of second messenger (cyclic AMP, Ins(1,4,5)P3) and mitogen-activated protein kinase (ERK and JNK) responses stimulated by the mACh receptor agonist methacholine were examined in CHO-m2m3 cells and compared to those stimulated in CHO-m2 and CHO-m3 cell-lines, ex...

  2. Bioprocess development for the production of mouse-human chimeric anti-epidermal growth factor receptor vIII antibody C12 by suspension culture of recombinant Chinese hamster ovary cells

    OpenAIRE

    Hu, Suwen; Deng, Lei; Wang, Huamao; Zhuang, Yingping; Chu, Ju; Zhang, Siliang; Li, Zhonghai; Guo, Meijin

    2011-01-01

    The mouse-human chimeric anti-epidermal growth factor receptor vIII (EGFRvIII) antibody C12 is a promising candidate for the diagnosis of hepatocellular carcinoma (HCC). In this study, 3 processes were successfully developed to produce C12 by cultivation of recombinant Chinese hamster ovary (CHO-DG44) cells in serum-free medium. The effect of inoculum density was evaluated in batch cultures of shaker flasks to obtain the optimal inoculum density of 5 × 105 cells/mL. Then, the basic metabolic ...

  3. Overleeft de hamster?

    NARCIS (Netherlands)

    Apeldoorn, van R.C.; Klein Douwel, C.; Thomas, P.

    1999-01-01

    Een analyse van de achteruitgang van de hamster (Cricetus cricetus) in Europa en Limburg, de oorzaken (veranderingen in de landbouw; versnippering van leefgebieden), en oplossingsrichtingen voor een duurzaam overleven van de hamster in Limburg (kernpopulaties in duurzame populatienetwerken)

  4. In vitro genotoxic and cytotoxic effects of ivermectin and its formulation ivomec on Chinese hamster ovary (CHO{sub K1}) cells

    Energy Technology Data Exchange (ETDEWEB)

    Molinari, G.; Soloneski, S.; Reigosa, M.A. [Catedra de Citologia, Facultad de Ciencias Naturales y Museo, Universidad Nacional de La Plata, La Plata (Argentina); Larramendy, M.L., E-mail: m_larramendy@hotmail.com [Catedra de Citologia, Facultad de Ciencias Naturales y Museo, Universidad Nacional de La Plata, La Plata (Argentina)

    2009-06-15

    The effects of ivermectin (IVM) and its commercial formulation ivomec (IVM 1.0%) were studied on Chinese hamster ovary (CHO{sub K1}) cells by several genotoxicity [sister chromatid exchange (SCE) and single cell gel electrophoresis (SCGE)] and cytotoxicity [cell-cycle progression (CCP), mitotic index (MI), proliferative replication index (PRI), 3(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), and neutral red (NR)] bioassays within the 1.0-250 {mu}g/ml concentration-range. While IVM and ivomec did not modified SCE frequencies, they induced DNA-strand breaks revealed by SCGE. An enhancement of slightly damaged cells and a decrease in undamaged cells were observed in IVM-treated cultures with 5.0-50.0 {mu}g/ml. In ivomec-treated cells, while an increase in slightly damaged cells was induced with 5.0-50.0 {mu}g/ml, the damaged and undamaged cells increased and decreased only with 50.0 {mu}g/ml. Both compounds exerted a delay in CCP and a reduction in PRI when 25.0 {mu}g/ml was employed whereas cytotoxicity was observed at higher concentration than 50.0 {mu}g/ml. No MI alteration was observed with 1.0-10.0 and 1.0-5.0 {mu}g/ml of IVM and ivomec, respectively. A concentration-related trend to an increase in MI was achieved within 1.0-10.0 {mu}g/ml. An increase in the MI was induced in 10.0 {mu}g/ml ivomec-treated cultures. A marked reduction of about 89% and 62% in regard to controls was observed with 25.0 {mu}g/ml of IVM and ivomec, respectively. NR and MTT assays revealed a cell growth inhibition when 0.25-250.0 {mu}g/ml of both compounds was employed. The results highlighted that IVM and ivomec exert both genotoxicity and cytotoxicity in mammalian cells in vitro, at least in CHO{sub K1} cells.

  5. Evaluation of the radio modifier effect of propolis on chinese hamster ovary (CHO-K1) and human prostate cancer (PC3) cells, irradiated with 60-CO

    International Nuclear Information System (INIS)

    In the last decades, it has been given a great interest to investigations concerning natural, effective, nontoxic compounds with radioprotective potential together with the increasing utilization of different types of ionizing radiation for various applications. Among them propolis, a resinous compound produced by honeybees (Apis mellifera), has been considered quite promising, since it presents several advantageous biological characteristics, i. e., anti-inflammatory, antimicrobial, anticarcinogenic, antioxidant and also free radical scavenging action. The purpose of the present study was to evaluate the effect of Brazilian propolis, collected in the State of Rio Grande do Sul, on Chinese hamster ovary (CHO-K1) and human prostate cancer (PC3) cells, irradiated with 60Co γ radiation. For this purpose, three interlinked parameters were analyzed: micronucleus induction, cell viability and clonogenic death. The choice of these parameters was justified by their biological significance, in addition to the fact that they are readily observable and measurable in irradiated cells. The cytogenetic data obtained showed a radioprotective effect of propolis (5-100 μg/ml) in the induction of DNA damage for both cell lines, irradiated with doses of 1 - 4 Gy. The cytotoxicity assay, however, showed a prominent antiproliferative effect of propolis (50 - 400μ/ml) in PC3 cells irradiated with 5 Gγ. The survival curves obtained were adequately fitted by a linear-quadratic model, where the α coefficient was higher in CHO-K1 cells. Concerning the clonogenic capacity, PC3 cells were more radiosensitive than CHO-K1 cells at the higher doses of the survival curve. Propolis at the concentrations of 30 - 100 μg/ml, did not influence the clonogenic potential of PC3 cells, since the survival curves, associated or not with propolis, were found similar, although the combined treatment in CHO-K1 cells exhibited a stimulating proliferative effect. The data obtained in vitro showed a

  6. Recombinant expression of human microsomal epoxide hydrolase protects V79 Chinese hamster cells from styrene oxide- but not from ethylene oxide-induced DNA strand breaks.

    Science.gov (United States)

    Herrero, M E; Arand, M; Hengstler, J G; Oesch, F

    1997-01-01

    Styrene 7,8-oxide and ethylene oxide are widely used genotoxic bulk chemicals, which have been associated with potential carcinogenic hazard for occupationally exposed workers. Both epoxides alkylate DNA preferentially at the N-7 position of guanine and consequently produce single-strand breaks and alkali labile sites in the DNA of exposed cells. In order to study the role of human microsomal epoxide hydrolase (hmEH) in protecting cells against genotoxicity of styrene 7,8-oxide and ethylene oxide, we expressed the cDNA of hmEH in V79 Chinese hamster cells. We obtained a number of cell clones that expressed functionally active epoxide hydrolase. Among these, the clone 92hmEH-V79 revealed an especially high enzymatic mEH activity toward styrene 7,8-oxide (10 nmol converted per mg of protein per min, measured in the 9,000 x g supernatant of the cell homogenate), that was 100 times higher than that determined in mock-transfected cells and within the range of mEH activity in human liver. Styrene 7,8-oxide-induced DNA single-strand breaks/alkali labile sites (dose range 10 microM to 1 mM styrene 7,8-oxide) measured by the alkaline elution technique were significantly lower in the 92hmEH-V79 cells as compared to the mock-transfected cells. The protection against styrene 7,8-oxide genotoxicity in 92hmEH-V79 cells could be abolished by addition of valpromide, a selective inhibitor of microsomal epoxide hydrolase. These results clearly show that the metabolism of styrene 7,8-oxide by hmEH in 92hmEH-V79 cells was responsible for the protection against styrene 7,8-oxide genotoxicity. On the other hand, no protective effect of epoxide hydrolase expression could be observed on ethylene oxide-induced DNA damage with the recombinant cell line over a dose range of 0.5-2.5 mM ethylene oxide. This selectivity of the protective effect on epoxide genotoxicity thus appears to be an important factor that must be taken into account for the prediction of the genotoxic risk of epoxides

  7. Moral Disengagement among Bystanders to School Bullying

    Science.gov (United States)

    Obermann, Marie-Louise

    2011-01-01

    This study examined the use of moral disengagement among children indirectly involved in bullying (bystanders). A sample of Danish adolescents (N = 660, M age 12.6 years) were divided into four groups depending on their bystander status: (a) outsiders, who did not experience bullying among their peers; (b) defenders, who were likely to help the…

  8. Evaluation of a bystander education program.

    Science.gov (United States)

    Amar, Angela Frederick; Sutherland, Melissa; Kesler, Erin

    2012-12-01

    Sexual and partner violence are widespread problems on college campuses. By changing attitudes, beliefs, and behavior, bystander education programs have been found to prevent sexual and partner violence and improve the responses of peers to survivors. The purpose of this study is to evaluate the effectiveness and feasibility of a bystander education program that was adapted to a specific university setting. A convenience sample of 202, full-time undergraduate students aged 18-22 years participated in the bystander education program and completed pre- and post-test measures of attitudes related to sexual and partner violence and willingness to help. Paired sample t-tests were used to examine changes in scores between pre- and post-test conditions. After the program, participants' reported decreased rape myth acceptance and denial of interpersonal violence, and increased intention to act as a bystander and an increased sense of responsibility to intervene. Mental health nurses can use principles of bystander education in violence prevention programs and in providing support to survivors. PMID:23215986

  9. 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

    Energy Technology Data Exchange (ETDEWEB)

    Kramer, J.M. (Miami Univ., Oxford, OH (USA). Dept. of Zoology)

    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.

  10. 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)

    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

  11. The role of non-protein sulphydryls in determining the chemical repair rates of free radical precursors of DNA damage and cell killing in Chinese hamster V79 cells

    International Nuclear Information System (INIS)

    Chinese hamster V79 fibroblasts were irradiated in the gas explosion apparatus and the chemical repair rates of the oxygen-dependent free radical precursors of DNA double-strand breaks (dsb) and lethal lesions measured using filter elution (pH 9.6) and a clonogenic assay. Depletion of cellular GSH levels, from 4.16 fmol/cell to 0.05 fmol/cell, by treatment with buthionine sulphoximine (50 μmol dm-3; 18 h), led to sensitization as regards DNA dsb induction and cell killing. This was evident at all time settings but was particularly pronounced when the oxygen shot was given 1 ms after the irradiation pulse. A detailed analysis of the chemical repair kinetics showed that depletion of GSH led to a reduction in the first-order rate constant for dsb precursors from 385 s-1 to 144 s-1, and for lethal lesion precursors from 533 s-1 to 165 s-1. (Author)

  12. THINDOWN IN RADIOBIOLOGY:E.COLI B/r,Bs—1,B.SUBTILUS SPORES,AND V—79 CHINESE HAMSTER CELLS

    Institute of Scientific and Technical Information of China (English)

    张纯祥; RobertKatz

    1995-01-01

    Track theory rested on the foundation of the radial distribution of dose from δ rays as the central contribution of atomic physics to heavy ion radiobiology,Here,a new calculation of the radial distribution of dose is applied,in which the classical angular distribtuion of dose of delta rays and a logarithmic polynomial representation of the electron range-energy relation are used.to form the basis of the present thindown calculation.Calculations of inactivation cross sections for heavy ions in the track width regime displaying thindown for E.Coli B/r and Bs-1,and for Bacillus Subtilus are straightforward for these are 1-hit detectors.Calculations for V-79 hamster cells are more complex.They follow the orginal development of this model for eucaryotic cells,and make use of the cross sections calculated for hypothetical internal targets which are then asserted to be proportional to the measured ceelular inactivation cross sections.The results are in reasonable agreement with experimental ,data.

  13. Brief report: The bystander effect in cyberbullying incidents.

    Science.gov (United States)

    Machackova, Hana; Dedkova, Lenka; Mezulanikova, Katerina

    2015-08-01

    This study examined the bystander effect in cyberbullying. Using self-reported data from 257 Czech respondents who had witnessed a cyberbullying attack, we tested whether provided help decreased with increased number of other bystanders. We controlled for several individual and contextual factors, including empathy, social self-efficacy, empathic response to victimization, and relationship to the victim. Results showed that participants tend to help the victims more in incidents with only one or two other bystanders. We also found that, as in the "offline" realm, bystander effect is not linear: no significant differences were found between incidents with a moderate number (3-10) and a larger number of total bystanders. Our findings, thus, provide support for the presence of the bystander effect in cyberbullying.

  14. Neutron induced bystander effect among zebrafish embryos

    Science.gov (United States)

    Ng, C. Y. P.; Kong, E. Y.; Kobayashi, A.; Suya, N.; Uchihori, Y.; Cheng, S. H.; Konishi, T.; Yu, K. N.

    2015-12-01

    The present paper reported the first-ever observation of neutron induced bystander effect (NIBE) using zebrafish (Danio rerio) embryos as the in vivo model. The neutron exposure in the present work was provided by the Neutron exposure Accelerator System for Biological Effect Experiments (NASBEE) facility at the National Institute of Radiological Sciences (NIRS), Chiba, Japan. Two different strategies were employed to induce NIBE, namely, through directly partnering and through medium transfer. Both results agreed with a neutron-dose window (20-50 mGy) which could induce NIBE. The lower dose limit corresponded to the threshold amount of neutron-induced damages to trigger significant bystander signals, while the upper limit corresponded to the onset of gamma-ray hormesis which could mitigate the neutron-induced damages and thereby suppress the bystander signals. Failures to observe NIBE in previous studies were due to using neutron doses outside the dose-window. Strategies to enhance the chance of observing NIBE included (1) use of a mono-energetic high-energy (e.g., between 100 keV and 2 MeV) neutron source, and (2) use of a neutron source with a small gamma-ray contamination. It appeared that the NASBEE facility used in the present study fulfilled both conditions, and was thus ideal for triggering NIBE.

  15. Evaluation of the radio modifier effect of propolis on chinese hamster ovary (CHO-K1) and human prostate cancer (PC3) cells, irradiated with 60-CO; Avaliacao do efeito radiomodificador da propolis em celulas de ovario de hamster chines (CHO-K1) e em celulas tumorais de prostata (PC3), irradiadas com CO-60

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Geyza Spigoti

    2011-07-01

    In the last decades, it has been given a great interest to investigations concerning natural, effective, nontoxic compounds with radioprotective potential together with the increasing utilization of different types of ionizing radiation for various applications. Among them propolis, a resinous compound produced by honeybees (Apis mellifera), has been considered quite promising, since it presents several advantageous biological characteristics, i. e., anti-inflammatory, antimicrobial, anticarcinogenic, antioxidant and also free radical scavenging action. The purpose of the present study was to evaluate the effect of Brazilian propolis, collected in the State of Rio Grande do Sul, on Chinese hamster ovary (CHO-K1) and human prostate cancer (PC3) cells, irradiated with {sup 60}Co {gamma} radiation. For this purpose, three interlinked parameters were analyzed: micronucleus induction, cell viability and clonogenic death. The choice of these parameters was justified by their biological significance, in addition to the fact that they are readily observable and measurable in irradiated cells. The cytogenetic data obtained showed a radioprotective effect of propolis (5-100 {mu}g/ml) in the induction of DNA damage for both cell lines, irradiated with doses of 1 - 4 Gy. The cytotoxicity assay, however, showed a prominent antiproliferative effect of propolis (50 - 400{mu}/ml) in PC3 cells irradiated with 5 G{gamma}. The survival curves obtained were adequately fitted by a linear-quadratic model, where the {alpha} coefficient was higher in CHO-K1 cells. Concerning the clonogenic capacity, PC3 cells were more radiosensitive than CHO-K1 cells at the higher doses of the survival curve. Propolis at the concentrations of 30 - 100 {mu}g/ml, did not influence the clonogenic potential of PC3 cells, since the survival curves, associated or not with propolis, were found similar, although the combined treatment in CHO-K1 cells exhibited a stimulating proliferative effect. The data

  16. The influence of melanin on bystander effect

    International Nuclear Information System (INIS)

    The influence of melanin on bystander effect has been studied. Melanin is known to be a natural substance with proved radioprotective properties. It is effective only against low dose radiation. The observed result in colony-forming activity of HPV-G cells may be due to the potential radioprotective effect of melanin. HPV-G cells (human keratinocyte line, immortalised by transfection with the HVP virus) are cultured in Dulbecco's MEM: F12 (1:1) Medium. In addition, 50 ml of Fetal Calf Serum, 5 ml penicillin-streptomycin, 5 ml L-glutamine and 1 g/ml of hydrocortisone were added to medium. Cells were maintained in an incubator at 37 degrees Celsius, with 95% humidity and 5% Carbon Dioxide and routinely subcultured every 8-10 days. Melanin was isolated from animal hair (Belarus Pharmaceutical Association, Minsk). Melanin was added to cell medium at 1 mg/l concentration. Cell suspension after dilution was counted using a Coulter counter. Appropriate cell numbers were plated according to the Puck and Marcus technique in 5 ml medium in 25cm2 NUNC flasks. There were 3 types of flasks: direct irradiation, bystander donor and bystander recipient. Each of 3 them had 4 triplet sets: control, melanin, irradiated cells 0,5 Gy and irradiated cells 0,5 Gy with melanin added. Melanin is added into flasks 30 min - 1 hour before irradiation. Bystander donor and direct flasks are irradiated and replaced back in the incubator at 37 degree centigrade for one hour. Culture flasks are irradiated at room temperature using a Co 60 teletherapy source, delivering approximately 2 Gy per minute at a source-to cell distance of 80 cm. 1 hour after irradiation the medium from bystander donor flasks is removed and filtered through NALGENE 0,2 m sterile syringe filter to ensure that no cells are present in the medium. This filtered medium is used to replace the medium from bystander recipient flasks. All flasks are left for 9-10 days (until colonies are visible) and then stained with Carbol Fusion

  17. Rape Myth Beliefs and Bystander Attitudes among Incoming College Students

    Science.gov (United States)

    McMahon, Sarah

    2010-01-01

    Objective: The bystander approach to rape prevention is gaining popularity on college campuses, although research is limited. This study explored bystander attitudes and their relationship with rape myths in a sample of college students. Participants: Surveys from 2,338 incoming undergraduate students at a large, northeastern university were…

  18. When bystanders become bothersome: The negative consequences of bystander conflict and the moderating role of resilience

    NARCIS (Netherlands)

    Erp, van Kim J.P.M; Rispens, Sonja; Gevers, Josette M.P.; Demerouti, Evangelia

    2014-01-01

    Bystander conflict is a situation in which employees are hindered in their work by parties not involved in the primary process. Public service employees and emergency care workers, such as ambulance employees and firefighters, often encounter this kind of conflict with potentially far-reaching detri

  19. The Bystander-Effect: A Meta-Analytic Review on Bystander Intervention in Dangerous and Non-Dangerous Emergencies

    Science.gov (United States)

    Fischer, Peter; Krueger, Joachim I.; Greitemeyer, Tobias; Vogrincic, Claudia; Kastenmuller, Andreas; Frey, Dieter; Heene, Moritz; Wicher, Magdalena; Kainbacher, Martina

    2011-01-01

    Research on bystander intervention has produced a great number of studies showing that the presence of other people in a critical situation reduces the likelihood that an individual will help. As the last systematic review of bystander research was published in 1981 and was not a quantitative meta-analysis in the modern sense, the present…

  20. Radioiodinated 4-iodo-L-meta-tyrosine, a system L selective artificial amino acid: molecular design and transport characterization in Chinese hamster ovary cells (CHO-K1 cells)

    International Nuclear Information System (INIS)

    Introduction: High expression of the system L amino acid transporter has been observed in clinically important tissues including tumors and the blood-brain barrier. We examined amino acid transport system L selectivity of 14C(U)-L-tyrosine (14C-Tyr), 125I-4-iodo-L-meta-tyrosine (4-125I-mTyr), 125I-6-iodo-L-meta-tyrosine (6-125I-mTyr), 125I-3-iodo-α-methyl-L-tyrosine (125I-IMT) and 125I-3-iodo-L-tyrosine (3-125I-Tyr) using Chinese hamster ovary cells (CHO-K1). Methods: Cells in the exponential growth phase were incubated with 18.5 kBq of labeled amino acid in 2 mL of phosphate-buffered saline-based uptake solution and an uptake solution with/without Na+ at 37oC or 4oC. We examined the effects of the following compounds (1.0 mM) on transport: 2-(methylamino)isobutyric acid (a specific inhibitor of system A, in Na+-containing uptake solution); 2-amino-bicyclo[2,2,1]heptane-2-carboxylic acid (a specific inhibitor of system L, in Na+-free uptake solution); sodium azide and 2,4-dinitrophenol (NaN3 and DNP, inhibitors of the generation of adenosine triphosphate); p-aminohippurate and tetraethylammonium (PAH and TEA, inhibitors of organic anion and cation transporters); and L- and D-isomers of natural amino acids. Results: 14C-Tyr exhibited affinity for systems L, A and ASC. 4-125I-mTyr and 3-125I-Tyr exhibited high specificity for system L, whereas 6-125I-mTyr and 125I-IMT exhibited affinity for both systems L and ASC. Uptake of 4-125I-mTyr was markedly reduced by incubation at 4 oC, and was not significantly inhibited by NaN3, DNP, PAH or TEA. The inhibition profiles of the L- and D-isomers of natural amino acids indicated that system L mediates the transport of 4-125I-mTyr. Conclusions: 4-125I-mTyr exhibited the greatest system L specificity (93.46±0.13%) of all of the tested amino acids.

  1. Intracellular transactivation of epidermal growth factor receptor by α1A-adrenoceptor is mediated by phosphatidylinositol 3-kinase independently of activation of extracellular signal regulated kinases 1/2 and serine-threonine kinases in Chinese hamster ovary cells.

    Science.gov (United States)

    Ulu, Nadir; Henning, Robert H; Guner, Sahika; Zoto, Teuta; Duman-Dalkilic, Basak; Duin, Marry; Gurdal, Hakan

    2013-10-01

    Transactivation of epidermal growth factor receptor (EGFR) by α1-adrenoceptor (α1-AR) is implicated in contraction and hypertrophy of vascular smooth muscle (VSM). We examine whether all α1-AR subtypes transactivate EGFR and explore the mechanism of transactivation. Chinese hamster ovary (CHO) cells stably expressing one subtype of α1-AR were transiently transfected with EGFR. The transactivation mechanism was examined both by coexpression of a chimeric erythropoietin (EPO)-EGFR with an extracellular EPO and intracellular EGFR domain, and by pharmacologic inhibition of external and internal signaling routes. All three α1-AR subtypes transactivated EGFR, which was dependent on the increase in intracellular calcium. The EGFR kinase inhibitor AG1478 [4-(3'-chloroanilino)-6,7-dimethoxyquinazoline] abrogated α1A-AR and α1D-AR induced phosphorylation of EGFR, but both the inhibition of matrix metalloproteinases by GM6001 [(R)-N4-hydroxy-N(1)-[(S)-2-(1H-indol-3-yl)-1-methylcarbamoyl-ethyl]-2-isobutyl-succinamide] or blockade of EGFR by cetuximab did not. Stimulation of α1A-AR and α1D-AR also induced phosphorylation of EPO-EGFR chimeric receptors. Moreover, α1A-AR stimulation enhanced phosphorylation of extracellular signal regulated kinase (ERK) 1/2 and serine-threonine kinases (Akt), which were both unaffected by AG1478, indicating that ERK1/2 and Akt phosphorylation is independent of EGFR transactivation. Accordingly, inhibitors of ERK1/2 or Akt did not influence the α1A-AR-mediated EGFR transactivation. Inhibition of calcium/calmodulin-dependent kinase II (CaMKII), phosphatidylinositol 3-kinase (PI3K), and Src, however, did block EGFR transactivation by α1A-AR and α1D-AR. These findings demonstrate that all α1-AR subtypes transactivate EGFR, which is dependent on an intracellular signaling route involving an increase in calcium and activation of CaMKII, PI3K, and Src, but not the of ERK1/2 and Akt pathways.

  2. Enteropathogenic Escherichia coli: foe or innocent bystander?

    Science.gov (United States)

    Hu, J; Torres, A G

    2015-08-01

    Enteropathogenic Escherichia coli (EPEC) remain one the most important pathogens infecting children and they are one of the main causes of persistent diarrhoea worldwide. Historically, typical EPEC (tEPEC), defined as those isolates with the attaching and effacement (A/E) genotype (eae(+)), which possess bfpA(+) and lack the stx(-) genes are found strongly associated with diarrhoeal cases. However, occurrence of atypical EPEC (aEPEC; eae(+)bfpA(-)stx(-)) in diarrhoeal and asymptomatic hosts has made investigators question the role of these pathogens in human disease. Current epidemiological data are helping to answer the question of whether EPEC is mainly a foe or an innocent bystander during infection.

  3. Mitochondrial mutagenesis induced by tumor-specific radiation bystander effects.

    LENUS (Irish Health Repository)

    Gorman, Sheeona

    2012-02-01

    The radiation bystander effect is a cellular process whereby cells not directly exposed to radiation display cellular alterations similar to directly irradiated cells. Cellular targets including mitochondria have been postulated to play a significant role in this process. In this study, we utilized the Random Mutation Capture assay to quantify the levels of random mutations and deletions in the mitochondrial genome of bystander cells. A significant increase in the frequency of random mitochondrial mutations was found at 24 h in bystander cells exposed to conditioned media from irradiated tumor explants (p = 0.018). CG:TA mutations were the most abundant lesion induced. A transient increase in the frequency of random mitochondrial deletions was also detected in bystander cells exposed to conditioned media from tumor but not normal tissue at 24 h (p = 0.028). The increase in both point mutations and deletions was transient and not detected at 72 h. To further investigate mitochondrial dysfunction, mitochondrial membrane potential and reactive oxygen species were assessed in these bystander cells. There was a significant reduction in mitochondrial membrane potential and this was positively associated with the frequency of random point mutation and deletions in bystander cells treated with conditioned media from tumor tissue (r = 0.71, p = 0.02). This study has shown that mitochondrial genome alterations are an acute consequence of the radiation bystander effect secondary to mitochondrial dysfunction and suggests that this cannot be solely attributable to changes in ROS levels alone.

  4. Radiation-induced bystander effects in vivo are sex specific

    Energy Technology Data Exchange (ETDEWEB)

    Koturbash, Igor; Kutanzi, Kristy; Hendrickson, Karl; Rodriguez-Juarez, Rocio; Kogosov, Dmitry [Department of Biological Sciences, University of Lethbridge, Alberta T1K 3M4 (Canada); Kovalchuk, Olga [Department of Biological Sciences, University of Lethbridge, Alberta T1K 3M4 (Canada)], E-mail: olga.kovalchuk@uleth.ca

    2008-07-03

    Ionizing radiation (IR) effects span beyond the area of direct exposure and can be observed in neighboring and distant naive cells and organs. This phenomenon is termed a 'bystander effect'. IR effects in directly exposed tissue in vivo are epigenetically mediated and distinct in males and females. Yet, IR-induced bystander effects have never been explored in a sex-specificity domain. We used an in vivo mouse model, whereby the bystander effects are studied in spleen of male and female animals subjected to head exposure when the rest of the body is protected by a medical-grade lead shield. We analyzed the induction of DNA damage and alterations in global DNA methylation. Molecular parameters were correlated with cellular proliferation and apoptosis levels. The changes observed in bystander organs are compared to the changes in unexposed animals and animals exposed to predicted and measured scatter doses. We have found the selective induction of DNA damage levels, global DNA methylation, cell proliferation and apoptosis in exposed and bystander spleen tissue of male and female mice. Sex differences were significantly diminished in animals subjected to a surgical removal of gonads. These data constitute the first evidence of sex differences in radiation-induced bystander effects in mouse spleen in vivo. We show the role of sex hormones in spleen bystander responses and discuss implications of the observed changes.

  5. The positive bystander effect: passive bystanders increase helping in situations with high expected negative consequences for the helper.

    Science.gov (United States)

    Fischer, Peter; Greitemeyer, Tobias

    2013-01-01

    The present field study investigated the interplay between the presence of a passive bystander (not present versus present) in a simulated bike theft and expected negative consequences (low versus high) in predicting intervention behavior when no physical victim is present. It was found that an additional bystander increases individual intervention in situations where the expected negative consequences for the helper in case of intervention were high (i.e., when the bike thief looks fierce) compared to situations where the expected negative consequences for the helper were low (i.e., when the bike thief does not look fierce). In contrast, no such effect for high vs. low expected negative consequences was observed when no additional bystander observed the critical situation. The results are discussed in light of previous laboratory findings on expected negative consequences and bystander intervention. PMID:23421000

  6. Radioprotection of targeted and bystander cells by methylproamine

    Energy Technology Data Exchange (ETDEWEB)

    Burdak-Rothkamm, Susanne [Queen' s University Belfast, Centre for Cancer Research and Cell Biology, Belfast (United Kingdom); Oxford University Hospitals, Cellular Pathology, Oxford (United Kingdom); Smith, Andrea; Lobachevsky, Pavel; Martin, Roger [Peter MacCallum Cancer Centre, Molecular Radiation Biology Laboratory, Melbourne (Australia); University of Melbourne, The Sir Peter MacCallum Department of Oncology, Melbourne (Australia); Prise, Kevin M. [Queen' s University Belfast, Centre for Cancer Research and Cell Biology, Belfast (United Kingdom)

    2014-09-23

    Radioprotective agents are of interest for application in radiotherapy for cancer and in public health medicine in the context of accidental radiation exposure. Methylproamine is the lead compound of a class of radioprotectors which act as DNA binding anti-oxidants, enabling the repair of transient radiation-induced oxidative DNA lesions. This study tested methylproamine for the radioprotection of both directly targeted and bystander cells. T98G glioma cells were treated with 15 μM methylproamine and exposed to {sup 137}Cs γ-ray/X-ray irradiation and He{sup 2+} microbeam irradiation. Radioprotection of directly targeted cells and bystander cells was measured by clonogenic survival or γH2AX assay. Radioprotection of directly targeted T98G cells by methylproamine was observed for {sup 137}Cs γ-rays and X-rays but not for He{sup 2+} charged particle irradiation. The effect of methylproamine on the bystander cell population was tested for both X-ray irradiation and He{sup 2+} ion microbeam irradiation. The X-ray bystander experiments were carried out by medium transfer from irradiated to non-irradiated cultures and three experimental designs were tested. Radioprotection was only observed when recipient cells were pretreated with the drug prior to exposure to the conditioned medium. In microbeam bystander experiments targeted and nontargeted cells were co-cultured with continuous methylproamine treatment during irradiation and postradiation incubation; radioprotection of bystander cells was observed. Methylproamine protected targeted cells from DNA damage caused by γ-ray or X-ray radiation but not He{sup 2+} ion radiation. Protection of bystander cells was independent of the type of radiation which the donor population received. (orig.) [German] Radioprotektive Agenzien sind sowohl in der Strahlentherapie von Krebserkrankungen als auch im Strahlenschutz im Zusammenhang mit akzidenteller Exposition von Bedeutung. Methylproamine ist die Leitsubstanz einer Klasse von

  7. Recursive mentalizing and common knowledge in the bystander effect.

    Science.gov (United States)

    Thomas, Kyle A; De Freitas, Julian; DeScioli, Peter; Pinker, Steven

    2016-05-01

    The more potential helpers there are, the less likely any individual is to help. A traditional explanation for this bystander effect is that responsibility diffuses across the multiple bystanders, diluting the responsibility of each. We investigate an alternative, which combines the volunteer's dilemma (each bystander is best off if another responds) with recursive theory of mind (each infers what the others know about what he knows) to predict that actors will strategically shirk when they think others feel compelled to help. In 3 experiments, participants responded to a (fictional) person who needed help from at least 1 volunteer. Participants were in groups of 2 or 5 and had varying information about whether other group members knew that help was needed. As predicted, people's decision to help zigzagged with the depth of their asymmetric, recursive knowledge (e.g., "John knows that Michael knows that John knows help is needed"), and replicated the classic bystander effect when they had common knowledge (everyone knowing what everyone knows). The results demonstrate that the bystander effect may result not from a mere diffusion of responsibility but specifically from actors' strategic computations.

  8. Gender differences in attitudes and beliefs associated with bystander behavior and sexual assault.

    Science.gov (United States)

    Amar, Angela F; Sutherland, Melissa; Laughon, Kathryn

    2014-01-01

    Sexual violence is a significant problem on many college campuses. Bystander education programs have been found to train individuals to act to prevent sexual and partner violence and improve the responses of peers to survivors. Limited evidence suggests that gender differences exist between males and females regarding both attitudes toward, and use of, bystander behavior, with females reporting more supportive attitudes and greater use of bystander behavior. The purpose of this study is to compare male and female college students on attitudes toward date rape, bystander efficacy, intention to act as a bystander, and actual use of bystander behaviors. A secondary aim explored gender differences in theoretically driven bystander behaviors and barriers to acting as a bystander. A convenience sample of 157 full-time undergraduate students aged 18-24 years completed survey measures of attitudes related to sexual and partner violence and willingness to help. Analysis of variance and chi-square were used to compare gender differences in scores. Significant gender differences were found for date rape attitudes, efficacy, and intention to act as a positive bystander. Men reported more rape-supportive attitudes and greater intention to act as a bystander than women, whereas women reported greater levels of bystander efficacy than men. The findings can be used in tailoring gender-specific components of bystander education programs for sexual assault prevention and intervention. PMID:24762431

  9. DMPD: TLR3 in antiviral immunity: key player or bystander? [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 16027039 TLR3 in antiviral immunity: key player or bystander? Schroder M, Bowie AG.... Trends Immunol. 2005 Sep;26(9):462-8. (.png) (.svg) (.html) (.csml) Show TLR3 in antiviral immunity: key pl...ayer or bystander? PubmedID 16027039 Title TLR3 in antiviral immunity: key player or bystander? Authors Schr

  10. Caffeine Markedly Enhanced Radiation-Induced Bystander Effects

    Institute of Scientific and Technical Information of China (English)

    JIANG Erkang; WU Lijun

    2009-01-01

    A bstract In this paper it is shown that incubation with 2 mM caffeine enhanced significantly the MN (micronucleus) formation in both the 1 cGy a-particle irradiated and non-irradiated by- stander regions. Moreover, caffeine treatment made the non-irradiated bystander cells more sensi- tive to damage signals. Treated by c-PTIO(2-(4-carboxy-phenyl)-4,4,5,5-tetramethyl-imidazoline- 1-oxyl-3-oxide), a nitric oxide (NO) scavenger, the MN frequencies were effectively inhibited, showing that nitric oxide might be very important in mediating the enhanced damage. These results indicated that caffeine enhanced the low dose a-particle radiation-induced damage in ir- radiated and non-irradiated bystander regions, and therefore it is important to investigate the relationship between the radiosensitizer and radiation-induced bystander effects (RIBE).

  11. Who intervenes against homophobic behavior? Attributes that distinguish active bystanders.

    Science.gov (United States)

    Poteat, V Paul; Vecho, Olivier

    2016-02-01

    Research on homophobic behavior has focused on students engaging in this behavior or students toward whom this behavior is directed. There has been little attention to the large segment of students who observe this behavior, including active bystanders who defend or support students when homophobic behavior occurs. Among 722 high school students (55% female, 87% white, 86% heterosexual), 66.8% had observed at least one instance of homophobic behavior in the past 30 days. Gender (in this case, girls more so than boys), leadership, courage, altruism, justice sensitivity, and number of LGBT friends were associated with engagement in more active bystander behavior in response to observing homophobic behavior. Further, gender, courage, altruism, and number of LGBT friends each made unique contributions in accounting for variability in students' defending behavior in a comprehensive regression model. Findings highlight qualities that interventionists should cultivate in students that could lead to more active bystander engagement against homophobic behavior. PMID:26790700

  12. Mechanism of bystander-blaming: defensive attribution, counterfactual thinking, and gender.

    Science.gov (United States)

    Levy, Inna; Ben-David, Sarah

    2015-01-01

    Contemporary victimology recognizes that an understanding of the mechanism of blaming requires a comprehensive approach that includes the victim, the offender, and the bystander. However, most of the existing research on blaming focuses on the victim and the offender, ignoring the issue of bystander-blaming. This study highlights the bystander and investigates bystander-blaming by exploring some theoretical explanations, including counterfactual thinking, defensive attribution, and gender differences. The study included 363 young male and female participants, who read vignettes describing the behavior of the victim and the bystander in a rape scenario and answered questions regarding bystander-blaming. The results show that both counterfactual thinking and defensive attribution play a role in bystander-blaming. This article addresses the theoretical and practical implications of these findings.

  13. Bullying victimization and the social and emotional maladjustment of bystanders: A propensity score analysis.

    Science.gov (United States)

    Werth, Jilynn M; Nickerson, Amanda B; Aloe, Ariel M; Swearer, Susan M

    2015-08-01

    This study investigated how bystanders, who have and have not been bullied, perceive their social and emotional maladjustment depending on the form of bullying (physical or verbal) they witness. Using propensity score matching, equivalent groups of 270 victimized and 270 non-victimized bystander groups were created based on middle school students' responses on the Bully Survey-Student Version (BYS-S; Swearer, 2001). Victimized bystanders experienced higher social maladjustment than non-victimized bystanders. Path analysis results suggest that social and emotional maladjustment as a bystander is related not only to social-emotional maladjustment as victim, but to gender and the form of bullying witnessed. The way in which bystanders are influenced by their personal victimization may be a critical factor in predicting, understanding, and increasing active bystander intervention. PMID:26270274

  14. 2-Amino-3,8-dimethylimidazo-[4,5-f]quinoxaline-induced DNA adduct formation and mutagenesis in DNA repair-deficient Chinese hamster ovary cells expressing human cytochrome P4501A1 and rapid or slow acetylator N-acetyltransferase 2.

    Science.gov (United States)

    Bendaly, Jean; Zhao, Shuang; Neale, Jason R; Metry, Kristin J; Doll, Mark A; States, J Christopher; Pierce, William M; Hein, David W

    2007-07-01

    2-Amino-3,8-dimethylimidazo-[4,5-f]quinoxaline (MeIQx) is one of the most potent and abundant mutagens in the western diet. Bioactivation includes N-hydroxylation catalyzed by cytochrome P450s followed by O-acetylation catalyzed by N-acetyltransferase 2 (NAT2). In humans, NAT2*4 allele is associated with rapid acetylator phenotype, whereas NAT2*5B allele is associated with slow acetylator phenotype. We hypothesized that rapid acetylator phenotype predisposes humans to DNA damage and mutagenesis from MeIQx. Nucleotide excision repair-deficient Chinese hamster ovary cells were constructed by stable transfection of human cytochrome P4501A1 (CYP1A1) and a single copy of either NAT2*4 (rapid acetylator) or NAT2*5B (slow acetylator) alleles. CYP1A1 and NAT2 catalytic activities were undetectable in untransfected Chinese hamster ovary cell lines. CYP1A1 activity did not differ significantly (P > 0.05) among the CYP1A1-transfected cell lines. Cells transfected with NAT2*4 had 20-fold significantly higher levels of sulfamethazine N-acetyltransferase (P = 0.0001) and 6-fold higher levels of N-hydroxy-MeIQx O-acetyltransferase (P = 0.0093) catalytic activity than cells transfected with NAT2*5B. Only cells transfected with both CYP1A1 and NAT2*4 showed concentration-dependent cytotoxicity and hypoxanthine phosphoribosyl transferase mutagenesis following MeIQx treatment. Deoxyguanosine-C8-MeIQx was the primary DNA adduct formed and levels were dose dependent in each cell line and in the following order: untransfected < transfected with CYP1A1 < transfected with CYP1A1 and NAT2*5B < transfected with CYP1A1 and NAT2*4. MeIQx DNA adduct levels were significantly higher (P < 0.001) in CYP1A1/NAT2*4 than CYP1A1/NAT2*5B cells at all concentrations of MeIQx tested. MeIQx-induced DNA adduct levels correlated very highly (r2 = 0.88) with MeIQx-induced mutants. These results strongly support extrahepatic activation of MeIQx by CYP1A1 and a robust effect of human NAT2 genetic polymorphism

  15. An “Intention-Focused” paradigm for improving bystander CPR performance□

    OpenAIRE

    Panchal, Ashish R.; Fishman, Jessica; Camp-Rogers, Teresa; Starodub, Roksolana; Merchant, Raina M.

    2014-01-01

    Despite public education campaigns and a chest compression-only initiative, bystander cardiopulmonary resuscitation (CPR) is provided in approximately 30–40% of out of hospital cardiac arrests in the United States. Bystander CPR rates may not improve without addressing factors influencing bystanders’ probability of performing CPR. We propose an “intention-focused” model for the bystander CPR performance utilizing validated behavioral theory. This model describes a framework that may predict C...

  16. Role of ATM in bystander signaling between human monocytes and lung adenocarcinoma cells.

    Science.gov (United States)

    Ghosh, Somnath; Ghosh, Anu; Krishna, Malini

    2015-12-01

    The response of a cell or tissue to ionizing radiation is mediated by direct damage to cellular components and indirect damage mediated by radiolysis of water. Radiation affects both irradiated cells and the surrounding cells and tissues. The radiation-induced bystander effect is defined by the presence of biological effects in cells that were not themselves in the field of irradiation. To establish the contribution of the bystander effect in the survival of the neighboring cells, lung carcinoma A549 cells were exposed to gamma-irradiation, 2Gy. The medium from the irradiated cells was transferred to non-irradiated A549 cells. Irradiated A549 cells as well as non-irradiated A549 cells cultured in the presence of medium from irradiated cells showed decrease in survival and increase in γ-H2AX and p-ATM foci, indicating a bystander effect. Bystander signaling was also observed between different cell types. Phorbol-12-myristate-13-acetate (PMA)-stimulated and gamma-irradiated U937 (human monocyte) cells induced a bystander response in non-irradiated A549 (lung carcinoma) cells as shown by decreased survival and increased γ-H2AX and p-ATM foci. Non-stimulated and/or irradiated U937 cells did not induce such effects in non-irradiated A549 cells. Since ATM protein was activated in irradiated cells as well as bystander cells, it was of interest to understand its role in bystander effect. Suppression of ATM with siRNA in A549 cells completely inhibited bystander effect in bystander A549 cells. On the other hand suppression of ATM with siRNA in PMA stimulated U937 cells caused only a partial inhibition of bystander effect in bystander A549 cells. These results indicate that apart from ATM, some additional factor may be involved in bystander effect between different cell types. PMID:26653982

  17. When being a bystander is not so innocent

    OpenAIRE

    Cox, Andrea L.; Siliciano, Robert F.

    2014-01-01

    A new mechanism to explain massive depletion of CD4+ T cells in HIV-1 infection despite the low frequency of productively infected cells involves innate immune sensing of HIV 1 by abortively infected “bystander” CD4+ T cells. The result is death of the bystander cells through an inflammatory process known as pyroptosis. These findings may provide long sought explanations for both CD4+ T cell depletion and HIV-associated inflammation. See Article on page X.

  18. Identifiable images of bystanders extracted from corneal reflections.

    Directory of Open Access Journals (Sweden)

    Rob Jenkins

    Full Text Available Criminal investigations often use photographic evidence to identify suspects. Here we combined robust face perception and high-resolution photography to mine face photographs for hidden information. By zooming in on high-resolution face photographs, we were able to recover images of unseen bystanders from reflections in the subjects' eyes. To establish whether these bystanders could be identified from the reflection images, we presented them as stimuli in a face matching task (Experiment 1. Accuracy in the face matching task was well above chance (50%, despite the unpromising source of the stimuli. Participants who were unfamiliar with the bystanders' faces (n = 16 performed at 71% accuracy [t(15 = 7.64, p<.0001, d = 1.91], and participants who were familiar with the faces (n = 16 performed at 84% accuracy [t(15 = 11.15, p<.0001, d = 2.79]. In a test of spontaneous recognition (Experiment 2, observers could reliably name a familiar face from an eye reflection image. For crimes in which the victims are photographed (e.g., hostage taking, child sex abuse, reflections in the eyes of the photographic subject could help to identify perpetrators.

  19. Do Sexual Assault Bystander Interventions Change Men's Intentions? Applying the Theory of Normative Social Behavior to Predicting Bystander Outcomes.

    Science.gov (United States)

    Mabry, Amanda; Turner, Monique Mitchell

    2016-01-01

    The high prevalence of sexual assault on college campuses has led to the implementation of health communication programs to prevent sexual assault. A few novel programs focus on primary prevention by targeting social norms related to gender and masculinity among men through bystander intervention. Guided by the theory of normative social behavior, this study sought to examine the relative effect of campaigns communicating positive versus negative injunctive norms and the interaction between exposure to such campaign messages and perceived descriptive norms and relevant cognitive moderators (e.g., outcome expectations, injunctive norms, group identity, ego involvement) among men. A 2 (high/low descriptive norms) × 2 (high/low moderator) × 3 (public service announcement) independent groups quasi-experimental design (N = 332) was used. Results indicated that messages communicating positive injunctive norms were most effective among men who were least likely to engage in bystander intervention. Furthermore, descriptive norms played a significant role in behavioral intentions, such that those with stronger norms were more likely to report intentions to engage in bystander behaviors in the future. Similarly, the moderators of aspiration, injunctive norms, social approval, and ego involvement had a significant positive effect on behavioral intentions. These findings have important implications for future message design strategy and audience segmentation. PMID:26716826

  20. Do Sexual Assault Bystander Interventions Change Men's Intentions? Applying the Theory of Normative Social Behavior to Predicting Bystander Outcomes.

    Science.gov (United States)

    Mabry, Amanda; Turner, Monique Mitchell

    2016-01-01

    The high prevalence of sexual assault on college campuses has led to the implementation of health communication programs to prevent sexual assault. A few novel programs focus on primary prevention by targeting social norms related to gender and masculinity among men through bystander intervention. Guided by the theory of normative social behavior, this study sought to examine the relative effect of campaigns communicating positive versus negative injunctive norms and the interaction between exposure to such campaign messages and perceived descriptive norms and relevant cognitive moderators (e.g., outcome expectations, injunctive norms, group identity, ego involvement) among men. A 2 (high/low descriptive norms) × 2 (high/low moderator) × 3 (public service announcement) independent groups quasi-experimental design (N = 332) was used. Results indicated that messages communicating positive injunctive norms were most effective among men who were least likely to engage in bystander intervention. Furthermore, descriptive norms played a significant role in behavioral intentions, such that those with stronger norms were more likely to report intentions to engage in bystander behaviors in the future. Similarly, the moderators of aspiration, injunctive norms, social approval, and ego involvement had a significant positive effect on behavioral intentions. These findings have important implications for future message design strategy and audience segmentation.

  1. The Influence of Parental Mental Health and Family Psychosocial Functioning on Bystander Behavior of Elementary School Children

    OpenAIRE

    Jenkins, Joanna C.

    2014-01-01

    Being the victim of school bullying is associated with many negative outcomes, including depression, anxiety, substance abuse, school refusal, and suicide. Peer bystanders are present in the majority of bullying situations and bystander intervention has been found to be very important in ending a bullying incident. However, most of the time bystanders do not step in to help the victim. The present study investigated the impact of parent and family influences on children’s bystander behavior. ...

  2. Student Voices: What Can Bystanders Do to Prevent Bullying of Students Who Are Different (or Perceived as Different) from Others?

    Science.gov (United States)

    Nordseth, Anna; Vepachedu, Vikas; Shipman, Grant; Alayachew, David

    2012-01-01

    In this article, four students share their ideas on what bystanders can do to prevent bullying of students who are different or perceived as different from others. Anna Nordseth says what bystanders need to realize is how to recognize bullying and what a lasting effect it can have on the individuals involved. One bold, compassionate bystander can…

  3. Establishment of a hamster lymphoma cell line

    Directory of Open Access Journals (Sweden)

    Abe,Shinji

    1974-08-01

    Full Text Available The establishment of a hamster lymphoma cell line was attempted. Simple mincing and trypsinization of lymphoma tissue resulted in a high degree of cell degeneration. The ascitic tumor cells produced by intraperitoneal transplantation of lymphoma tissue gave a better result. These ascitic cells grew and were cultured successively in medium consisting of RPMI 1640 and 20% fetal calf serum. Cells were round and grew in suspension. Accelerated cell growth was observed one month after starting the culture. In the stained preparations, cells were lymphoblastic. Cells were transplantable into new-born hamsters and produced tumors, but not in young adult hamsters.

  4. Individual Motivations and Characteristics Associated with Bystander Intervention during Bullying Episodes among Children and Youth

    Science.gov (United States)

    Cappadocia, M. Catherine; Pepler, Debra; Cummings, Joanne G.; Craig, Wendy

    2012-01-01

    The aim of the current study was to explore bystander experiences during bullying episodes among children and youth attending a residential summer camp by investigating rates of witnessing and intervention, as well as individual motivations and characteristics associated with bystander intervention. The majority of children had witnessed bullying…

  5. Effects of a Rape Awareness Program on College Women: Increasing Bystander Efficacy and Willingness to Intervene

    Science.gov (United States)

    Foubert, John D.; Langhinrichsen-Rohling, Jennifer; Brasfield, Hope; Hill, Brent

    2010-01-01

    An experimental study evaluated the efficacy of a sexual assault risk-reduction program on 279 college women that focused on learning characteristics of male perpetrators and teaching bystander intervention techniques. After seeing The Women's Program, participants reported significantly greater bystander efficacy and significantly greater…

  6. What Would You Do? Strategies for Bystander Intervention to Prevent Sexual Violence by College Students

    Science.gov (United States)

    McMahon, Sarah; Hoffman, Melanie Lowe; McMahon, Sheila M.; Zucker, Sharon; Koenick, Ruth Anne

    2013-01-01

    Bystander education is an increasingly utilized strategy for addressing sexual assault prevention and intervention on U.S. college campuses. Given the paramount importance of peers among college students, what types of pro-social bystander interventions do students themselves deem feasible in the campus context? Drawing on self-reports from…

  7. On Standby? A Comparison of Online and Offline Witnesses to Bullying and Their Bystander Behaviour

    Science.gov (United States)

    Quirk, Roslynn; Campbell, Marilyn

    2015-01-01

    Given their ubiquitous presence as witnesses to school-yard bullying, the role of the "bystander" has been studied extensively. The prevalence and behaviour of bystanders to "cyberbullying," however, is less understood. In an anonymous, school-based questionnaire, 716 secondary school students from South-East Queensland…

  8. Contributions of Personal and Situational Factors to Bystanders' Reactions to School Bullying

    Science.gov (United States)

    Oh, Insoo; Hazler, Richard J.

    2009-01-01

    The intent of this study was to explore bystanders' personal and situational variables predicting their behavioural reactions to school bullying by investigating a sample of 298 college students who had witnessed bullying during middle or high school. Results indicated that the bystander personal variables, gender and past experience as a bully or…

  9. Booze, Bars, and Bystander Behavior: People Who Consumed Alcohol Help Faster in the Presence of Others

    NARCIS (Netherlands)

    Bommel, van Marco; Prooijen, Jan-Willem; Elffers, Henk; Lange, van Paul A.M.

    2016-01-01

    People help each other less often and less quickly when bystanders are present. In this paper, we propose that alcohol consumption could attenuate or reverse this so-called bystander effect. Alcohol impairs people cognitively and perceptually, leading them to think less about the presence of others

  10. 人源靶向补体抑制物CR2-CD59在中国仓鼠卵巢细胞中的稳定表达%Stable expression of targeting complement inhibitor CR2-CD59 in Chinese hamster ovary cells

    Institute of Scientific and Technical Information of China (English)

    郭彦; 周育森; 寇志华; 孙世惠; 张传福; 赵光宇; 于虹; 宋宏彬; 乔飞; 陈万荣

    2010-01-01

    目的 构建人源靶向补体抑制物CR2-CD59,并筛选中国仓鼠卵巢细胞(Chinese hamster ovary cell,CHO)高效表达细胞株. 方法 运用FuGENE 6转染试剂,将含有人CR2-CD59的重组PEE14.1质粒转入CHO细胞,蛋氨酸亚氨基代砜(MSX)筛选出阳性克隆,并利用无血清培养基对CHO细胞表达株进行培养获得重组蛋白,以ELISA、SDS-PAGE和Western blot对表达蛋白进行鉴定. 结果 成功构建PEE14.1-CR2-CD59重组质粒,获得CHO细胞稳定表达株.SDS-PAGE结果 表明,重组蛋白CR2-CD59的相对分子质量同预期结果 一致.ELISA和Western blot鉴定重组蛋白CR2-CD59可与CR2、CD59多克隆抗体特异性结合.且与含血清培养基相比,无血清培养基能明显提高CHO细胞的蛋白表达量(P<0.05).结论 在CHO细胞中成功表达人源靶向补体抑制物CR2-CD59.

  11. Measurement of the bystander intervention model for bullying and sexual harassment.

    Science.gov (United States)

    Nickerson, Amanda B; Aloe, Ariel M; Livingston, Jennifer A; Feeley, Thomas Hugh

    2014-06-01

    Although peer bystanders can exacerbate or prevent bullying and sexual harassment, research has been hindered by the absence of a validated assessment tool to measure the process and sequential steps of the bystander intervention model. A measure was developed based on the five steps of Latané and Darley's (1970) bystander intervention model applied to bullying and sexual harassment. Confirmatory factor analysis with a sample of 562 secondary school students confirmed the five-factor structure of the measure. Structural equation modeling revealed that all the steps were influenced by the previous step in the model, as the theory proposed. In addition, the bystander intervention measure was positively correlated with empathy, attitudes toward bullying and sexual harassment, and awareness of bullying and sexual harassment facts. This measure can be used for future research and to inform intervention efforts related to the process of bystander intervention for bullying and sexual harassment. PMID:24793386

  12. Adolescent bystanders' perspectives of aggression in the online versus school environments.

    Science.gov (United States)

    Patterson, Lisa J; Allan, Alfred; Cross, Donna

    2016-06-01

    Researchers' understanding of bystanders' perspectives in the cyber-environment fails to take young people's perceptions into account and remains imperfect. Interventions encouraging adolescents to help targets of cyber-aggression are therefore typically based upon traditional school-based aggression research. Twenty-four in-depth interviews with Australian 13-16 year-olds revealed two themes that reflect how young bystanders perceive differences between aggression online and at school. The physical presence theme suggests that young bystanders struggle to determine online intentions in the absence of body language, leading to hesitancy in reactions and furthermore make it easier for them to ignore online transgressions and avoid becoming involved. The authority theme indicates young bystanders perceive that, compared to the school environment, the online environment lacks clearly established rules, authority figures and formal reporting mechanisms. These differences indicate that unique strategies should be developed to encourage young bystanders to intervene in cyber-aggression situations.

  13. Measurement of the bystander intervention model for bullying and sexual harassment.

    Science.gov (United States)

    Nickerson, Amanda B; Aloe, Ariel M; Livingston, Jennifer A; Feeley, Thomas Hugh

    2014-06-01

    Although peer bystanders can exacerbate or prevent bullying and sexual harassment, research has been hindered by the absence of a validated assessment tool to measure the process and sequential steps of the bystander intervention model. A measure was developed based on the five steps of Latané and Darley's (1970) bystander intervention model applied to bullying and sexual harassment. Confirmatory factor analysis with a sample of 562 secondary school students confirmed the five-factor structure of the measure. Structural equation modeling revealed that all the steps were influenced by the previous step in the model, as the theory proposed. In addition, the bystander intervention measure was positively correlated with empathy, attitudes toward bullying and sexual harassment, and awareness of bullying and sexual harassment facts. This measure can be used for future research and to inform intervention efforts related to the process of bystander intervention for bullying and sexual harassment.

  14. Induction of lyme arthritis in LSH hamsters

    Energy Technology Data Exchange (ETDEWEB)

    Schmitz, J.L.; Schell, R.F.; Hejka, A.; England, D.M.; Konick, L.

    1988-09-01

    In studies of experimental Lyme disease, a major obstacle has been the unavailability of a suitable animal model. We found that irradiated LSH/Ss Lak hamsters developed arthritis after injection of Borrelia burgdorferi in the hind paws. When nonirradiated hamsters were injected in the hind paws with B. burgdorferi, acute transient synovitis was present. A diffuse neutrophilic infiltrate involved the synovia and periarticular structures. The inflammation was associated with edema, hyperemia, and granulation tissue. Numerous spirochetes were seen in the synovial and subsynovial tissues. The histopathologic changes were enhanced in irradiated hamsters. The onset and duration of the induced swelling were dependent on the dose of radiation and the inoculum of spirochetes. Inoculation of irradiated hamsters with Formalin-killed spirochetes or medium in which B. burgdorferi had grown for 7 days failed to induce swelling. This animal model should prove useful for studies of the immune response to B. burgdorferi and the pathogenesis of Lyme arthritis.

  15. Induction of lyme arthritis in LSH hamsters

    International Nuclear Information System (INIS)

    In studies of experimental Lyme disease, a major obstacle has been the unavailability of a suitable animal model. We found that irradiated LSH/Ss Lak hamsters developed arthritis after injection of Borrelia burgdorferi in the hind paws. When nonirradiated hamsters were injected in the hind paws with B. burgdorferi, acute transient synovitis was present. A diffuse neutrophilic infiltrate involved the synovia and periarticular structures. The inflammation was associated with edema, hyperemia, and granulation tissue. Numerous spirochetes were seen in the synovial and subsynovial tissues. The histopathologic changes were enhanced in irradiated hamsters. The onset and duration of the induced swelling were dependent on the dose of radiation and the inoculum of spirochetes. Inoculation of irradiated hamsters with Formalin-killed spirochetes or medium in which B. burgdorferi had grown for 7 days failed to induce swelling. This animal model should prove useful for studies of the immune response to B. burgdorferi and the pathogenesis of Lyme arthritis

  16. Mycoplasma pneumoniae-induced hydrocephalus in hamsters.

    OpenAIRE

    Kohn, D F; Chinookoswong, N; Wang, J

    1984-01-01

    Hydrocephalus was induced in neonatal hamsters after intracerebral inoculation of Mycoplasma pneumoniae. Examination of the ependyma from affected animals by electron microscopy did not reveal mycoplasma. However, in an ependymal organ culture system, M. pneumoniae cytadsorbed to ependymal cells.

  17. Personal distress and the influence of bystanders on responding to an emergency.

    Science.gov (United States)

    Hortensius, Ruud; Schutter, Dennis J L G; de Gelder, Beatrice

    2016-08-01

    Spontaneous helping behavior during an emergency is influenced by the personality of the onlooker and by social situational factors such as the presence of bystanders. Here, we sought to determine the influences of sympathy, an other-oriented response, and personal distress, a self-oriented response, on the effect of bystanders during an emergency. In four experiments, we investigated whether trait levels of sympathy and personal distress predicted responses to an emergency in the presence of bystanders by using behavioral measures and single-pulse transcranial magnetic stimulation. Sympathy and personal distress were expected to be associated with faster responses to an emergency without bystanders present, but only personal distress would predict slower responses to an emergency with bystanders present. The results of a cued reaction time task showed that people who reported higher levels of personal distress and sympathy responded faster to an emergency without bystanders (Exp. 1). In contrast to our predictions, perspective taking but not personal distress was associated with slower reaction times as the number of bystanders increased during an emergency (Exp. 2). However, the decrease in motor corticospinal excitability, a direct physiological measure of action preparation, with the increase in the number of bystanders was solely predicted by personal distress (Exp. 3). Incorporating cognitive load manipulations during the observation of an emergency suggested that personal distress is linked to an effect of bystanders on reflexive responding to an emergency (Exp. 4). Taken together, these results indicate that the presence of bystanders during an emergency reduces action preparation in people with a disposition to experience personal distress. PMID:27126708

  18. Risk Factors Associated with Peer Victimization and Bystander Behaviors among Adolescent Students

    Science.gov (United States)

    Huang, Zepeng; Liu, Zhenni; Liu, Xiangxiang; Lv, Laiwen; Zhang, Yan; Ou, Limin; Li, Liping

    2016-01-01

    Despite the prevalence of the phenomena of peer victimization and bystander behaviors, little data has generated to describe their relationships and risk factors. In this paper, a self-administered survey using a cross-sectional cluster-random sampling method in a sample of 5450 participants (2734 girls and 2716 boys) between 4th and 11th grades was conducted at six schools (two primary schools and four middle schools) located in Shantou, China. Self-reported peer victimization, bystander behaviors and information regarding parents’ risky behaviors and individual behavioral factors were collected. Multinomial logistic regression analysis was applied to evaluate risk factors affecting peer victimization and bystander behaviors. The results indicated that urban participants were more likely to become bullying victims but less likely to become passive bystanders. Contrarily, bullying victimization was related to the increasing of passive bystander behaviors. Father drinking and mother smoking as independent factors were risk factors for peer victimization. Participants who were smoking or drinking had a tendency to be involved in both peer victimization and passive bystander behaviors. This study suggested that bystander behaviors, victims’ and parents’ educations play a more important role in peer victimization than previously thought. PMID:27472354

  19. Risk Factors Associated with Peer Victimization and Bystander Behaviors among Adolescent Students.

    Science.gov (United States)

    Huang, Zepeng; Liu, Zhenni; Liu, Xiangxiang; Lv, Laiwen; Zhang, Yan; Ou, Limin; Li, Liping

    2016-01-01

    Despite the prevalence of the phenomena of peer victimization and bystander behaviors, little data has generated to describe their relationships and risk factors. In this paper, a self-administered survey using a cross-sectional cluster-random sampling method in a sample of 5450 participants (2734 girls and 2716 boys) between 4th and 11th grades was conducted at six schools (two primary schools and four middle schools) located in Shantou, China. Self-reported peer victimization, bystander behaviors and information regarding parents' risky behaviors and individual behavioral factors were collected. Multinomial logistic regression analysis was applied to evaluate risk factors affecting peer victimization and bystander behaviors. The results indicated that urban participants were more likely to become bullying victims but less likely to become passive bystanders. Contrarily, bullying victimization was related to the increasing of passive bystander behaviors. Father drinking and mother smoking as independent factors were risk factors for peer victimization. Participants who were smoking or drinking had a tendency to be involved in both peer victimization and passive bystander behaviors. This study suggested that bystander behaviors, victims' and parents' educations play a more important role in peer victimization than previously thought. PMID:27472354

  20. Bystander effect induced by UV radiation; why should we be interested?

    Science.gov (United States)

    Widel, Maria

    2012-11-14

    The bystander effect, whose essence is an interaction of cells directly subjected to radiation with adjacent non-subjected cells, via molecular signals, is an important component of ionizing radiation action. However, knowledge of the bystander effect in the case of ultraviolet (UV) radiation is quite limited. Reactive oxygen and nitrogen species generated by UV in exposed cells induce bystander effects in non-exposed cells, such as reduction in clonogenic cell survival and delayed cell death, oxidative DNA damage and gene mutations, induction of micronuclei, lipid peroxidation and apoptosis. Although the bystander effect after UV radiation has been recognized in cell culture systems, its occurrence in vivo has not been studied. However, solar UV radiation, which is the main source of UV in the environment, may induce in human dermal tissue an inflammatory response and immune suppression, events which can be considered as bystander effects of UV radiation. The oxidative damage to DNA, genomic instability and the inflammatory response may lead to carcinogenesis. UV radiation is considered one of the important etiologic factors for skin cancers, basal- and squamous-cell carcinomas and malignant melanoma. Based on the mechanisms of actions it seems that the UV-induced bystander effect can have some impact on skin damage (carcinogenesis?), and probably on cells of other tissues. The paper reviews the existing data about the UV-induced bystander effect and discusses a possible implication of this phenomenon for health risk. 

  1. Radiation-induced bystander effect in non-irradiated glioblastoma spheroid cells

    International Nuclear Information System (INIS)

    Radiation-induced bystander effects (RIBEs) are detected in cells that are not irradiated but receive signals from treated cells. The present study explored these bystander effects in a U87MG multicellular tumour spheroid model. A medium transfer technique was employed to induce the bystander effect, and colony formation assay was used to evaluate the effect. Relative changes in expression of BAX, BCL2, JNK and ERK genes were analysed using RT-PCR to investigate the RIBE mechanism. A significant decrease in plating efficiency was observed for both bystander and irradiated cells. The survival fraction was calculated for bystander cells to be 69.48% and for irradiated cells to be 34.68%. There was no change in pro-apoptotic BAX relative expression, but anti-apoptotic BCL2 showed downregulation in both irradiated and bystander cells. Pro-apoptotic JNK in bystander samples and ERK in irradiated samples were upregulated. The clonogenic survival data suggests that there was a classic RIBE in U87MG spheroids exposed to 4 Gy of X-rays, using a medium transfer technique. Changes in the expression of pro- and anti-apoptotic genes indicate involvement of both intrinsic apoptotic and MAPK pathways in inducing these effects. (author)

  2. Spatio-temporal analysis of tamoxifen-induced bystander effects in breast cancer cells using microfluidics.

    Science.gov (United States)

    Rios-Mondragon, Ivan; Wang, Xiang; Gerdes, Hans-Hermann

    2012-06-01

    The bystander effect in cancer therapy is the inhibition or killing of tumor cells that are adjacent to those directly affected by the agent used for treatment. In the case of chemotherapy, little is known as to how much and by which mechanisms bystander effects contribute to the elimination of tumor cells. This is mainly due to the difficulty to distinguish between targeted and bystander cells since both are exposed to the pharmaceutical compound. We here studied the interaction of tamoxifen-treated human breast cancer MCF-7 cells with their neighboring counterparts by exploiting laminar flow patterning in a microfluidic chip to ensure selective drug delivery. The spatio-temporal evolution of the bystander response in non-targeted cells was analyzed by measuring the mitochondrial membrane potential under conditions of free diffusion. Our data show that the bystander response is detectable as early as 1 hour after drug treatment and reached effective distances of at least 2.8 mm. Furthermore, the bystander effect was merely dependent on diffusible factors rather than cell contact-dependent signaling. Taken together, our study illustrates that this microfluidic approach is a promising tool for screening and optimization of putative chemotherapeutic drugs to maximize the bystander response in cancer therapy. PMID:23750189

  3. The development of bystander intentions and social-moral reasoning about intergroup verbal aggression.

    Science.gov (United States)

    Palmer, Sally B; Rutland, Adam; Cameron, Lindsey

    2015-11-01

    A developmental intergroup approach was taken to examine the development of prosocial bystander intentions among children and adolescents. Participants as bystanders (N = 260) aged 8-10 and 13-15 years were presented with scenarios of direct aggression between individuals from different social groups (i.e., intergroup verbal aggression). These situations involved either an ingroup aggressor and an outgroup victim or an outgroup aggressor and an ingroup victim. This study focussed on the role of intergroup factors (group membership, ingroup identification, group norms, and social-moral reasoning) in the development of prosocial bystander intentions. Findings showed that prosocial bystander intentions declined with age. This effect was partially mediated by the ingroup norm to intervene and perceived severity of the verbal aggression. However, a moderated mediation analysis showed that only when the victim was an ingroup member and the aggressor an outgroup member did participants become more likely with age to report prosocial bystander intentions due to increased ingroup identification. Results also showed that younger children focussed on moral concerns and adolescents focussed more on psychological concerns when reasoning about their bystander intention. These novel findings help explain the developmental decline in prosocial bystander intentions from middle childhood into early adolescence when observing direct intergroup aggression.

  4. Prosocial Bystander Behavior in Bullying Dynamics: Assessing the Impact of Social Capital.

    Science.gov (United States)

    Evans, Caroline B R; Smokowski, Paul R

    2015-12-01

    Individuals who observe a bullying event, but are not directly involved as a bully or victim, are referred to as bystanders. Prosocial bystanders are those individuals who actively intervene in bullying dynamics to support the victim and this prosocial behavior often ends the bullying. The current study examines how social capital in the form of social support, community engagement, mental health functioning, and positive school experiences and characteristics is associated with the likelihood of engaging in prosocial bystander behavior in a large sample (N = 5752; 51.03% female) of racially/ethnically diverse rural youth. It was hypothesized that social capital would be associated with an increased likelihood of engaging in prosocial bystander behavior. Following multiple imputation, an ordered logistic regression with robust standard errors was run. The hypothesis was partially supported and results indicated that social capital in the form of friend and teacher support, ethnic identity, religious orientation, and future optimism were significantly associated with an increased likelihood of engaging in prosocial bystander behavior. Contrary to the hypothesis, a decreased rate of self-esteem was significantly associated with an increased likelihood of engaging in prosocial bystander behavior. The findings highlight the importance of positive social relationships and community engagement in increasing prosocial bystander behavior and ultimately decreasing school bullying. Implications were discussed.

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

    Science.gov (United States)

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

    2015-07-01

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

  6. A three-step purification strategy for isolation of hamster TIG2 from CHO cells: characterization of two processed endogenous forms.

    Science.gov (United States)

    Busmann, Annette; Walden, Michael; Wendland, Martin; Kutzleb, Christian; Forssmann, Wolf-Georg; John, Harald

    2004-11-25

    We have recently isolated a bioactive, circulating protein of human tazarotene-induced gene-2 (TIG2) as the natural ligand of the orphan receptor ChemR23. Here we describe a simplified method for the isolation of hamster TIG2 protein from Chinese hamster ovary (CHO) cell supernatant. Using a heparin-affinity column followed by two reversed phase chromatography steps resulted in the isolation of pure biologically active material. Two processed bioactive forms of Chinese hamster TIG2 were identified by Edman sequencing and matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF-MS) mass fingerprint analysis, representing the amino acid residues T20 to F156, and T20 to A155 of the 163 amino acid propeptide. Comparison with the predicted aa-sequence indicates a mutation or modification within the C-terminal end of the peptide. PMID:15522723

  7. 胞外唾液酸酶造成工程中国仓鼠卵巢细胞株所产人源重组促红素唾液酸含量降低%Extracellular sialidase degrades sialic acid in recombinant human erythropoietin produced by an industrial Chinese hamster ovary cell strain

    Institute of Scientific and Technical Information of China (English)

    刘颖慰; 周祥山; 刘海峰; 宋志伟; 张元兴

    2012-01-01

    To investigate the N-glycosylation characteristics of recombinant human erythropoietin (rhEPO) produced by an industrial Chinese hamster ovary (CHO) cell line that is currently used in a large scale manufacturing process, we cultured this cell strain in static mode. The produced rhEPO in the culture supernatant was analyzed using isoelectric focusing (IEF) and Ricinus communis agglutinin-I (RCA-I) lectin precipitation. The lactate dehydrogenase (LDH) and sialidase activity in the serum-free supernatant were assayed as well. The analyses revealed that this cell strain could produce rhEPO with high sialic acid content, but during prolonged culture, cell viability decreased with time whilst the activity of sialidase present in the supernatant increased. The loss in rhEPO quality was due to a decrease in terminal sialic acid on the N-glycans, caused by sialidase degradation. The methods and findings in this paper serve as basis for further investigation of industrial production process.%为了对工程中国仓鼠卵巢(CHO)细胞所产人源重组促红素(rhEPO)的N-糖基化特点进行考察,静置培养工程细胞后,通过等电聚焦和凝集素共沉淀对培养上清中的rhEPO进行分析,并对无血清培养上清中乳酸脱氢酶(LDH)和唾液酸酶活性进行检测,发现这株CHO细胞可以表达唾液酸含量较高的rhEPO蛋白.但是随着培养时间的延长,细胞的存活率逐渐降低,死亡的细胞将胞内的唾液酸酶释放到胞外,唾液酸酶的降解作用会造成N-糖链分枝末端的唾液酸占有率降低,导致rhEPO蛋白糖基化形态的变化.所使用的方法及得到的结果为进一步对工业过程进行分析提供了参考.

  8. 重组乙型肝炎疫苗(中国仓鼠卵巢细胞)免疫12年的效果研究%12 Years Immunological Effects of Hepatitis B Vaccine Made by Recombinant Deoxyribonucleic Acid Techniques in Chinese Hamster Ovary Cell

    Institute of Scientific and Technical Information of China (English)

    齐顺祥; 王锋; 张勇; 毕胜利; 张新江; 张建立; 张志勇; 郝志勇; 陈吉朝; 褚娟; 马景臣; 赵玉良

    2010-01-01

    目的 研究1997~1999年出生人群,接种重组乙型肝炎(乙肝)疫苗[Hepatitis B Vaccine Made by Recombinant Deoxyrlbonucleic Acid(DNA)Techniques in Chinese Hamster Ovary(CHO)Cell,HepB(CHO)]的免疫效果.方法 将正定县1997~1999年出生人群接种重组HepB(CHO)的三个乡作为研究现场,以户籍登记在册的全部儿童为研究对象,核实重组HepB(CHO)接种史,采集静脉血5ml,无菌分离血清,使用固相放射免疫试剂检测乙肝病毒表面抗原[Hepatitis B Virus(HBV)Surface Antigen,HBsAg]和抗乙肝病毒核心抗原抗体(Anti-HBV Core Antibody,Anti-HBc):抗乙肝病毒表面抗原抗体(Anti-HBV Surface Antibody,Anti-HBs)使用Abbott公司生产的微粒子酶免疫测定(Microparticle Enzyme lmmunoassay,MEIA)试剂定量检测.结果 免疫后10~12年的AntiHBs阳性率分别为71.0%、72.1%、68.2%,平均70.3%;Anti-HBs的几何平均浓度(Geometric Mean Concentration,GMC)分别为197.9mIU/ml(毫国际单位/毫升)、296.0mIU/ml、158.0mIU/ml,平均207.9mIU/ml.HBsAg阳性率为0.50%,Anti-HBc阳性率为2.26%.结论 重组HepB(CHO)免疫后10~12年效果良好.

  9. SV40 DNA amplification and reintegration in surviving hamster cells after 60Co γ-irradiation

    International Nuclear Information System (INIS)

    SV40-transformed Chinese hamster embryo cells were exposed to 60Co γ-irradiation and the fate of the integrated SV40 sequences was pursued over a period of 20 days following radiation exposure. As shown by colony hybridization, integrated SV40 sequences were amplified in surviving and non-surviving cells. At later times, however, clonal sublines of surviving cells grown for 20-30 cell generations after irradiation had lost most of their amplified SV40 copies but showed altered restriction fragment patterns indicating reintegration of SV40 sequences at new sites of the hamster genome. This suggest that 60Co γ-irradiation can generate mutations by inducing over-replication of chromosome segments that are then substrates of enzymatic rearrangements. (author)

  10. Histopathology of Lyme arthritis in LSH hamsters

    Energy Technology Data Exchange (ETDEWEB)

    Hejka, A.; Schmitz, J.L.; England, D.M.; Callister, S.M.; Schell, R.F.

    1989-05-01

    The authors studied the histopathologic evolution of arthritis in nonirradiated and irradiated hamsters infected with Borrelia burgdorferi. Nonirradiated hamsters injected in the hind paws with B. burgdorferi developed an acute inflammatory reaction involving the synovium, periarticular soft tissues, and dermis. This acute inflammatory reaction was short-lived and was replaced by a mild chronic synovitis as the number of detectable spirochetes in the synovium, periarticular soft tissues, and perineurovascular areas diminished. Exposing hamsters to radiation before inoculation with B. burgdorferi exacerbated and prolonged the acute inflammatory phase. Spirochetes also persisted longer in the periarticular soft tissues. A major histopathologic finding was destructive and erosive bone changes of the hind paws, which resulted in deformation of the joints. These studies should be helpful in defining the immune mechanism participating in the onset, progression, and resolution of Lyme arthritis.

  11. Histopathology of Lyme arthritis in LSH hamsters

    International Nuclear Information System (INIS)

    The authors studied the histopathologic evolution of arthritis in nonirradiated and irradiated hamsters infected with Borrelia burgdorferi. Nonirradiated hamsters injected in the hind paws with B. burgdorferi developed an acute inflammatory reaction involving the synovium, periarticular soft tissues, and dermis. This acute inflammatory reaction was short-lived and was replaced by a mild chronic synovitis as the number of detectable spirochetes in the synovium, periarticular soft tissues, and perineurovascular areas diminished. Exposing hamsters to radiation before inoculation with B. burgdorferi exacerbated and prolonged the acute inflammatory phase. Spirochetes also persisted longer in the periarticular soft tissues. A major histopathologic finding was destructive and erosive bone changes of the hind paws, which resulted in deformation of the joints. These studies should be helpful in defining the immune mechanism participating in the onset, progression, and resolution of Lyme arthritis

  12. Decreased adult neurogenesis in hibernating Syrian hamster.

    Science.gov (United States)

    León-Espinosa, Gonzalo; García, Esther; Gómez-Pinedo, Ulises; Hernández, Félix; DeFelipe, Javier; Ávila, Jesús

    2016-10-01

    Generation of new neurons from adult neural stem cells occurs in the dentate gyrus (DG) of the hippocampus and the lateral walls of the lateral ventricles. In this article, we study the neurogenesis that takes place during the hibernation of the Syrian hamster (Mesocricetus auratus). Using a variety of standard neurogenesis markers and 5-bromo-2-deoxyuridine (BrdU) incorporation, we describe a preferential decrease in the proliferation of newborn neurons in the subventricular zone (SVZ) of the hibernating hamsters (torpor) rather than in the hippocampus. Furthermore, we demonstrate that the proliferative capacity is recovered after 3-4days of torpor when arousal is triggered under natural conditions (i.e., not artificially provoked). In addition, we show that tau3R, a tau isoform with three microtubule-binding domains, is a suitable marker to study neurogenesis both in the SVZ and subgranular zone (SGZ) of the Syrian hamster brain. PMID:27436535

  13. Contribution to the normal fecal flora of the hamster: Proteus mirabilis in normal feces of hamster

    Directory of Open Access Journals (Sweden)

    Genesio Pacheco

    1955-05-01

    Full Text Available Proteus mirabilis must be considered a normal inhabitant of the intestine of hamsters. It is also found in the vaginal secretion of females of this animal, when in oestrus.1 Os hamsters são parasitados pelos Proteus. 2 As amostras isoladas foram identificadas ao Pr. mirabilis de Hauser. 3 O Proteus isolado não revelou ação patogênica sôbre camundongos mas se mostrou patogênico para cobaias. 4 O germen era presente na secreção vaginal de hamsters, na época do cio.

  14. When can I help? A conceptual framework for the prevention of sexual violence through bystander intervention.

    Science.gov (United States)

    McMahon, Sarah; Banyard, Victoria L

    2012-01-01

    The bystander intervention approach is gaining popularity as a means for engaging communities in sexual assault prevention, especially on college campuses. Many bystander programs are teaching community members how to intervene without first assisting them to identify the full range of opportunities when they can intervene. In this article, the authors review the literature on sexual violence bystander intervention and present a conceptual framework that lays out a continuum of bystander opportunities ranging from reactive situations after an assault has occurred, to situations before an assault has occurred (posing high to low risk to victims), as well as proactive situations where no risk to the victim is present. The implications of this typology are discussed in the context of program development, evaluation, and further research. PMID:22096017

  15. Bystander effects and their implications for clinical radiation therapy: Insights from multiscale in silico experiments.

    Science.gov (United States)

    Powathil, Gibin G; Munro, Alastair J; Chaplain, Mark A J; Swat, Maciej

    2016-07-21

    Radiotherapy is a commonly used treatment for cancer and is usually given in varying doses. At low radiation doses relatively few cells die as a direct response to radiation but secondary radiation effects, such as DNA mutation or bystander phenomena, may affect many cells. Consequently it is at low radiation levels where an understanding of bystander effects is essential in designing novel therapies with superior clinical outcomes. In this paper, we use a hybrid multiscale mathematical model to study the direct effects of radiation as well as radiation-induced bystander effects on both tumour cells and normal cells. We show that bystander responses play a major role in mediating radiation damage to cells at low-doses of radiotherapy, doing more damage than that due to direct radiation. The survival curves derived from our computational simulations showed an area of hyper-radiosensitivity at low-doses that are not obtained using a traditional radiobiological model. PMID:27084360

  16. Morbidity among bystanders of bullying behavior at school: concepts, concerns, and clinical/research issues.

    Science.gov (United States)

    Rivers, Ian

    2012-01-01

    The role of the bystander is not one that is easily understood in the anti-bullying literature. Roles within the unofficial hierarchy of the school-yard and playground overlap considerably, and each role has its own social dynamic that brings with it a shifting behavioral landscape that affects every student. In this article, the mental health correlates of three categories of bystander are explored: the co-victim, the isolate, and the confederate. Each category of bystander has its own characterizations and mental health correlates. Reports of post-traumatic stress, internalized hostility, substance use, and suicide ideation are discussed with reference to studies involving witnesses of family abuse, community and school violence as well as bullying. It is argued that bystanders are the key to challenging bullying in schools, and their mental health and well-being is pivotal to the effectiveness of anti-bullying interventions. PMID:22909907

  17. Heart rate modulation in bystanding geese watching social and non-social events

    NARCIS (Netherlands)

    Wascher, Claudia A. F.; Scheiber, Isabella B. R.; Kotrschal, Kurt

    2008-01-01

    Simply observing other individuals interacting has been shown to affect subsequent behaviour and also hormones in 'bystander' individuals. However, immediate physiological responses of an observer have been hardly investigated. Here we present results on individuals' heart rate (HR) responses during

  18. A Web-Based Sexual Violence Bystander Intervention for Male College Students: Randomized Controlled Trial

    OpenAIRE

    Salazar, Laura F.; Vivolo-Kantor, Alana; Hardin, James; Berkowitz, Alan

    2014-01-01

    Background Bystander intervention approaches offer promise for reducing rates of sexual violence on college campuses. Most interventions are in-person small-group formats, which limit their reach and reduce their overall public health impact. Objective This study evaluated the efficacy of RealConsent, a Web-based bystander approach to sexual violence prevention, in enhancing prosocial intervening behaviors and preventing sexual violence perpetration. Methods A random probability sample of 743...

  19. A Role for Bioelectric Effects in the Induction of Bystander Signals by Ionizing Radiation?

    OpenAIRE

    Mothersill, C; Moran, G; McNeill, F.; Gow, M.D.; Denbeigh, J.; Prestwich, W.; Seymour, C. B.

    2007-01-01

    The induction of “bystander effects” i.e. effects in cells which have not received an ionizing radiation track, is now accepted but the mechanisms are not completely clear. Bystander effects following high and low LET radiation exposure are accepted but mechanisms are still not understood. There is some evidence for a physical component to the signal. This paper tests the hypothesis that bioelectric or biomagnetic phenomena are involved. Human immortalized skin keratinocytes and primary expla...

  20. Der Bystander-Effekt in alltäglichen Hilfesituationen : ein nicht-reaktives Feldexperiment

    OpenAIRE

    Alle, Katrin; Mayerl, Jochen

    2010-01-01

    "Der These der Verantwortungsdiffusion zufolge sinkt die Wahrscheinlichkeit einer Hilfeleistung, wenn mehrere Zeugen eine Hilfesituation beobachten, da sich aufgrund der Anwesenheit mehrerer potentieller Helfer die individuell wahrgenommene Verantwortung reduziert (sog. Bystander-Effekt). Die vorliegende Arbeit stellt Ergebnisse eines nicht-reaktiven Feldexperiments mit verdeckter Beobachtung zur Untersuchung des Bystander-Effekts in einer ungefährlichen alltäglichen Hilfesituation mit 80 Ver...

  1. Der Bystander-Effekt in alltäglichen Hilfesituationen : ein nicht-reaktives Feldexperiment

    OpenAIRE

    Alle, Katrin; Mayerl, Jochen

    2010-01-01

    Der These der Verantwortungsdiffusion zufolge sinkt die Wahrscheinlichkeit einer Hilfeleistung, wenn mehrere Zeugen eine Hilfesituation beobachten, da sich aufgrund der Anwesenheit mehrerer potentieller Helfer die individuell wahrgenommene Verantwortung reduziert (sog. Bystander-Effekt). Die vorliegende Arbeit stellt Ergebnisse eines nicht-reaktiven Feldexperiments mit verdeckter Beobachtung zur Untersuchung des Bystander-Effekts in einer ungefährlichen alltäglichen Hilfesituation mit 80 Vers...

  2. Bystander behavior in bullying situations : basic moral sensitivity, moral disengagement and defender self-efficacy

    OpenAIRE

    Thornberg, Robert; Jungert, Tomas

    2013-01-01

    The aim of the present study was to investigate how basic moral sensitivity in bullying, moral disengagement in bullying and defender self-efficacy were related to different bystander behaviors in bullying. Therefore, we examined pathways that linked students' basic moral sensitivity, moral disengagement, and defender self-efficacy to different bystander behaviors in bullying situations. Three hundred and forty-seven teenagers completed a bullying survey. Findings indicated that compared with...

  3. The Effect of a Class-wide Training on Prosocial Bystander Behaviors

    OpenAIRE

    Barnes, Charity Deanne

    2015-01-01

    The purpose of this study was to decrease school bullying by implementing a class-wide intervention that targets bystanders. Hypotheses include that an intervention will increase prosocial bystander behaviors that will result in reduced rates of bullying and improved positive peer responses. Ross and Horner’s Positive Behavior Supports bullying prevention program was modified to increase incentives for students who defend others from bullying. A multiple baseline design across three general e...

  4. Bystander motivation in bullying incidents : To intervene or not to intervene?

    OpenAIRE

    Thornberg, Robert; Tenenbaum, Laura; Varjas, Kristen; Meyers, Joel; Jungert, Tomas; Vanegas, Gina

    2012-01-01

    Introduction: This research sought to extend knowledge about bystanders in bullying situations with a focus on the motivations that lead them to different responses. The 2 primary goals of this study were to investigate the reasons for children’s decisions to help or not to help a victim when witnessing bullying, and to generate a grounded theory (or conceptual framework) of bystander motivation in bullying situations. Methods: Thirty students ranging in age from 9 to 15 years (M=11....

  5. Booze, Bars, and Bystander Behavior: People who Consumed Alcohol Help Faster in the Presence of Others.

    OpenAIRE

    Marco eVan Bommel; Jan-Willem eVan Prooijen; Henk eElffers; Paul evan Lange

    2016-01-01

    People help each other less often and less quickly when bystanders are present. In this paper, we propose that alcohol consumption could attenuate or reverse this so-called bystander effect. Alcohol impairs people cognitively and perceptually, leading them to think less about the presence of others and behave less inhibited. Moreover, alcohol makes people more prone to see the benefits of helping and not the costs. To provide an initial test of these lines of reasoning, we invited visitors o...

  6. Bystanders' responses to offline bullying and cyberbullying: The role of empathy and normative beliefs about aggression.

    Science.gov (United States)

    Machackova, Hana; Pfetsch, Jan

    2016-04-01

    Cyberbullying often takes place with the virtual presence or knowledge of bystanders. While we have some evidence about the determinants of bystanders' responses to offline bullying, we lack empirical studies concerning the variables that influence bystanders' responses to cyberbullying. The current study examines bystanders' responses to offline bullying and cyberbullying incidents. Two types of responses were captured: support toward the victims and the reinforcement of bullies' actions. Using data from 321 German adolescents (ages 12-18; M = 14.99; 44% girls), the association between bystanders' responses and normative beliefs about verbal aggression and cyberaggression, and affective and cognitive empathy, were tested in a path model. Both types of normative beliefs positively predicted the reinforcement of bullies, and normative belief about verbal aggression also predicted support for the victims of offline bullying. Both types of empathy predicted support in offline bullying, but only affective empathy predicted support in cyberbullying. There was no link between affective or cognitive empathy to the reinforcement of bullies. Moreover, bystanders' tendencies to respond supportively to the victim or to reinforce the bully were rather consistent in both cyber- and offline bullying, but there was no link between support and reinforcement. The findings are discussed with regard to implications for prevention and intervention efforts.

  7. Autophagy promotes radiation-induced senescence but inhibits bystander effects in human breast cancer cells.

    Science.gov (United States)

    Huang, Yao-Huei; Yang, Pei-Ming; Chuah, Qiu-Yu; Lee, Yi-Jang; Hsieh, Yi-Fen; Peng, Chih-Wen; Chiu, Shu-Jun

    2014-07-01

    Ionizing radiation induces cellular senescence to suppress cancer cell proliferation. However, it also induces deleterious bystander effects in the unirradiated neighboring cells through the release of senescence-associated secretory phenotypes (SASPs) that promote tumor progression. Although autophagy has been reported to promote senescence, its role is still unclear. We previously showed that radiation induces senescence in PTTG1-depleted cancer cells. In this study, we found that autophagy was required for the radiation-induced senescence in PTTG1-depleted breast cancer cells. Inhibition of autophagy caused the cells to switch from radiation-induced senescence to apoptosis. Senescent cancer cells exerted bystander effects by promoting the invasion and migration of unirradiated cells through the release of CSF2 and the subsequently activation of the JAK2-STAT3 and AKT pathways. However, the radiation-induced bystander effects were correlated with the inhibition of endogenous autophagy in bystander cells, which also resulted from the activation of the CSF2-JAK2 pathway. The induction of autophagy by rapamycin reduced the radiation-induced bystander effects. This study reveals, for the first time, the dual role of autophagy in radiation-induced senescence and bystander effects.

  8. Bystanders' responses to offline bullying and cyberbullying: The role of empathy and normative beliefs about aggression.

    Science.gov (United States)

    Machackova, Hana; Pfetsch, Jan

    2016-04-01

    Cyberbullying often takes place with the virtual presence or knowledge of bystanders. While we have some evidence about the determinants of bystanders' responses to offline bullying, we lack empirical studies concerning the variables that influence bystanders' responses to cyberbullying. The current study examines bystanders' responses to offline bullying and cyberbullying incidents. Two types of responses were captured: support toward the victims and the reinforcement of bullies' actions. Using data from 321 German adolescents (ages 12-18; M = 14.99; 44% girls), the association between bystanders' responses and normative beliefs about verbal aggression and cyberaggression, and affective and cognitive empathy, were tested in a path model. Both types of normative beliefs positively predicted the reinforcement of bullies, and normative belief about verbal aggression also predicted support for the victims of offline bullying. Both types of empathy predicted support in offline bullying, but only affective empathy predicted support in cyberbullying. There was no link between affective or cognitive empathy to the reinforcement of bullies. Moreover, bystanders' tendencies to respond supportively to the victim or to reinforce the bully were rather consistent in both cyber- and offline bullying, but there was no link between support and reinforcement. The findings are discussed with regard to implications for prevention and intervention efforts. PMID:26946454

  9. Damaging and protective bystander cross-talk between human lung cancer and normal cells after proton microbeam irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Desai, Sejal [Radiation Signalling and Cancer Biology Section, Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400 085 (India); Kobayashi, Alisa; Konishi, Teruaki; Oikawa, Masakazu [Radiation System and Engineering Section, Department of Technical Support and Development, Research, Development and Support Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Pandey, Badri N., E-mail: badrinarain@yahoo.co.in [Radiation Signalling and Cancer Biology Section, Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400 085 (India)

    2014-05-15

    Graphical abstract: - Highlights: • Proton-microbeam irradiated A549 cells send damaging signals to bystander A549 cells. • Irradiated A549–A549 bystander response is through gap junctional communication. • Bystander WI38 cells exert protective signalling in irradiated A549 cells. • Rescue of irradiated A549 cells by WI38 cells is independent of gap junctions. - Abstract: Most of the studies of radiation-induced bystander effects (RIBE) have been focused on understanding the radiobiological changes observed in bystander cells in response to the signals from irradiated cells in a normal cell population with implications to radiation risk assessment. However, reports on RIBE with relevance to cancer radiotherapy especially investigating the bidirectional and criss-cross bystander communications between cancer and normal cells are limited. Hence, in present study employing co-culture approach, we have investigated the bystander cross-talk between lung cancer (A549) and normal (WI38) cells after proton-microbeam irradiation using γ-H2AX foci fluorescence as a measure of DNA double-strand breaks (DSBs). We observed that in A549–A549 co-cultures, irradiated A549 cells exert damaging effects in bystander A549 cells, which were found to be mediated through gap junctional intercellular communication (GJIC). However, in A549–WI38 co-cultures, irradiated A549 did not affect bystander WI38 cells. Rather, bystander WI38 cells induced inverse protective signalling (rescue effect) in irradiated A549 cells, which was independent of GJIC. On the other hand, in response to irradiated WI38 cells neither of the bystander cells (A549 or WI38) showed significant increase in γ-H2AX foci. The observed bystander signalling between tumour and normal cells may have potential implications in therapeutic outcome of cancer radiotherapy.

  10. Nipah virus transmission in a hamster model.

    Directory of Open Access Journals (Sweden)

    Emmie de Wit

    2011-12-01

    Full Text Available Based on epidemiological data, it is believed that human-to-human transmission plays an important role in Nipah virus outbreaks. No experimental data are currently available on the potential routes of human-to-human transmission of Nipah virus. In a first dose-finding experiment in Syrian hamsters, it was shown that Nipah virus was predominantly shed via the respiratory tract within nasal and oropharyngeal secretions. Although Nipah viral RNA was detected in urogenital and rectal swabs, no infectious virus was recovered from these samples, suggesting no viable virus was shed via these routes. In addition, hamsters inoculated with high doses shed significantly higher amounts of viable Nipah virus particles in comparison with hamsters infected with lower inoculum doses. Using the highest inoculum dose, three potential routes of Nipah virus transmission were investigated in the hamster model: transmission via fomites, transmission via direct contact and transmission via aerosols. It was demonstrated that Nipah virus is transmitted efficiently via direct contact and inefficiently via fomites, but not via aerosols. These findings are in line with epidemiological data which suggest that direct contact with nasal and oropharyngeal secretions of Nipah virus infected individuals resulted in greater risk of Nipah virus infection. The data provide new and much-needed insights into the modes and efficiency of Nipah virus transmission and have important public health implications with regards to the risk assessment and management of future Nipah virus outbreaks.

  11. Ahne hamster lõikuskuul/ Tambet Kaugema

    Index Scriptorium Estoniae

    Kaugema, Tambet

    2010-01-01

    Eesti Nuku- ja Noorsoteatri jõululavastusest "Ahne hamster ja värvilised jäälilled", autor Miloš Macourek, tõlkija Leo Metsar, lavastaja ja muusikaline kujundaja Virko Annus, mängib Tarmo Männard. Esietendus 21. novembril Köismäe tornis

  12. Bystander effects induced by the low-fluence irradiation of carbon and iron ions (6 MeV/n)

    International Nuclear Information System (INIS)

    Many reports are available regarding bystander effects after exposure to low fluences of alpha particles and helium ions. However, few studies have examined bystander cellular effects after exposure to low fluences of ion species heavier than helium. We has been investigating bystander effects using both human normal fibroblasts and tumor cell lines irradiated with low energy (6 MeV/n) carbon or iron ions generated with the Medium Energy Beam Course. This year we focused on the bystander cellular effects as follows; Bystander cell-killing effect in human tumor cell lines irradiated with carbon ions. Relationship of bystander lethal effect between p53-wild and p53-mutated cells. Bystander cell-killing effect was observed in human normal and tumor cells harboring wild-type p53, but not in p53-mutated tumor cells. Moreover, observed bystander effect was suppressed by treating with a specific inhibitor of gap-junction mediated cell-cell communication. There is evidence that p53- and gap-junction-related bystander effect is an important role of carbon-ion induced lethal effect. (author)

  13. RAD9 deficiency enhances radiation induced bystander DNA damage and transcriptomal response

    International Nuclear Information System (INIS)

    Radiation induced bystander effects are an important component of the overall response of cells to irradiation and are associated with human health risks. The mechanism responsible includes intra-cellular and inter-cellular signaling by which the bystander response is propagated. However, details of the signaling mechanism are not well defined. We measured the bystander response of Mrad9+/+ and Mrad9−/− mouse embryonic stem cells, as well as human H1299 cells with inherent or RNA interference-mediated reduced RAD9 levels after exposure to 1 Gy α particles, by scoring chromosomal aberrations and micronuclei formation, respectively. In addition, we used microarray gene expression analyses to profile the transcriptome of directly irradiated and bystander H1299 cells. We demonstrated that Mrad9 null enhances chromatid aberration frequency induced by radiation in bystander mouse embryonic stem cells. In addition, we found that H1299 cells with reduced RAD9 protein levels showed a higher frequency of radiation induced bystander micronuclei formation, compared with parental cells containing inherent levels of RAD9. The enhanced bystander response in human cells was associated with a unique transcriptomic profile. In unirradiated cells, RAD9 reduction broadly affected stress response pathways at the mRNA level; there was reduction in transcript levels corresponding to genes encoding multiple members of the UVA-MAPK and p38MAPK families, such as STAT1 and PARP1, suggesting that these signaling mechanisms may not function optimally when RAD9 is reduced. Using network analysis, we found that differential activation of the SP1 and NUPR1 transcriptional regulators was predicted in directly irradiated and bystander H1299 cells. Transcription factor prediction analysis also implied that HIF1α (Hypoxia induced factor 1 alpha) activation by protein stabilization in irradiated cells could be a negative predictor of the bystander response, suggesting that local hypoxic stress

  14. An extracellular DNA mediated bystander effect produced from low dose irradiated endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Ermakov, Aleksei V., E-mail: avePlato@mail.ru [Research Centre for Medical Genetics, Russian Academy of Medical Sciences, Moscow (Russian Federation); Konkova, Marina S.; Kostyuk, Svetlana V.; Smirnova, Tatiana D.; Malinovskaya, Elena M.; Efremova, Liudmila V.; Veiko, Natalya N. [Research Centre for Medical Genetics, Russian Academy of Medical Sciences, Moscow (Russian Federation)

    2011-07-01

    The human umbilical vein endothelial cells culture was exposed to X-ray radiation in a low dose of 10 cGy. The fragments of extracellular genomic DNA (ecDNA{sup R}) were isolated from the culture medium after the short-term incubation. A culture medium of unirradiated endothelial cells was then supplemented with ecDNA{sup R}, followed by analysing the cells along the series of parameters (bystander effect). The exposed cells and bystander endotheliocytes showed similar response to low doses: approximation of the 1q12 loci of chromosome 1 and their transposition into the cellular nucleus, change in shape of the endotheliocytic nucleus, activation of the nucleolus organizing regions (NORs), actin polymerization, and an elevated level of DNA double-stranded breaks. Following blockade of TLR9 receptors with oligonucleotide-inhibitor or chloroquine in the bystander cells these effects - except of activation of NORs - on exposure to ecDNA{sup R} disappeared, with no bystander response thus observed. The presence of the radiation-induced apoptosis in the bystander effect being studied suggests a possibility for radiation-modified ecDNA fragments (i.e., stress signaling factors) to be released into the culture medium, whereas inhibition of TLR9 suggests the binding these ligands to the recipient cells. A similar DNA-signaling pathway in the bystander effect we previously described for human lymphocytes. Integrity of data makes it possible to suppose that a similar signaling mechanism which we demonstrated for lymphocytes (humoral system) might also be mediated in a monolayer culture of cells (cellular tissue) after the development of the bystander effect in them and transfer of stress signaling factors (ecDNA{sup R}) through the culture medium.

  15. Target irradiation induced bystander effects between stem-like and non stem-like cancer cells

    International Nuclear Information System (INIS)

    Highlights: • Existence of radiation induced bystander effects (RIBE) between cancer stem-like cells (CSCs) and non stem-like cancer cells (NSCCs) in human fibrosarcoma HT1080 cells. • Existence of significant difference in generation and response of bystander signals between CSCs and NSCCs. • CSCs are significantly less sensitive to NO scavenger than that of NSCCs in terms of DNA double strand breaks induced by RIBE. - Abstract: Tumors are heterogeneous in nature and consist of multiple cell types. Among them, cancer stem-like cells (CSCs) are suggested to be the principal cause of tumor metastasis, resistance and recurrence. Therefore, understanding the behavior of CSCs in direct and indirect irradiations is crucial for clinical radiotherapy. Here, the CSCs and their counterpart non stem-like cancer cells (NSCCs) in human HT1080 fibrosarcoma cell line were sorted and labeled, then the two cell subtypes were mixed together and chosen separately to be irradiated via a proton microbeam. The radiation-induced bystander effect (RIBE) between the CSCs and NSCCs was measured by imaging 53BP1 foci, a widely used indicator for DNA double strand break (DSB). CSCs were found to be less active than NSCCs in both the generation and the response of bystander signals. Moreover, the nitric oxide (NO) scavenger c-PTIO can effectively alleviate the bystander effect in bystander NSCCs but not in bystander CSCs, indicating a difference of the two cell subtypes in NO signal response. To our knowledge, this is the first report shedding light on the RIBE between CSCs and NSCCs, which might contribute to a further understanding of the out-of-field effect in cancer radiotherapy

  16. Target irradiation induced bystander effects between stem-like and non stem-like cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yu [State Key Laboratory of Nuclear Physics and Technology, School of Physics, Peking University, Beijing 100871 (China); Space Radiation Research Unit, International Open Laboratory, National Institute of Radiological Sciences, 4-9-1 Inage-ku, Chiba 263-8555 (Japan); Kobayashi, Alisa [Space Radiation Research Unit, International Open Laboratory, National Institute of Radiological Sciences, 4-9-1 Inage-ku, Chiba 263-8555 (Japan); Department of Technical Support and Development, National Institute of Radiological Sciences, 4-9-1 Inage-ku, Chiba 263-8555 (Japan); Maeda, Takeshi [Department of Technical Support and Development, National Institute of Radiological Sciences, 4-9-1 Inage-ku, Chiba 263-8555 (Japan); Fu, Qibin [State Key Laboratory of Nuclear Physics and Technology, School of Physics, Peking University, Beijing 100871 (China); Oikawa, Masakazu [Department of Technical Support and Development, National Institute of Radiological Sciences, 4-9-1 Inage-ku, Chiba 263-8555 (Japan); Yang, Gen, E-mail: gen.yang@pku.edu.cn [State Key Laboratory of Nuclear Physics and Technology, School of Physics, Peking University, Beijing 100871 (China); Space Radiation Research Unit, International Open Laboratory, National Institute of Radiological Sciences, 4-9-1 Inage-ku, Chiba 263-8555 (Japan); Konishi, Teruaki, E-mail: tkonishi@nirs.go.jp [Space Radiation Research Unit, International Open Laboratory, National Institute of Radiological Sciences, 4-9-1 Inage-ku, Chiba 263-8555 (Japan); Department of Technical Support and Development, National Institute of Radiological Sciences, 4-9-1 Inage-ku, Chiba 263-8555 (Japan); Uchihori, Yukio [Space Radiation Research Unit, International Open Laboratory, National Institute of Radiological Sciences, 4-9-1 Inage-ku, Chiba 263-8555 (Japan); Department of Technical Support and Development, National Institute of Radiological Sciences, 4-9-1 Inage-ku, Chiba 263-8555 (Japan); and others

    2015-03-15

    Highlights: • Existence of radiation induced bystander effects (RIBE) between cancer stem-like cells (CSCs) and non stem-like cancer cells (NSCCs) in human fibrosarcoma HT1080 cells. • Existence of significant difference in generation and response of bystander signals between CSCs and NSCCs. • CSCs are significantly less sensitive to NO scavenger than that of NSCCs in terms of DNA double strand breaks induced by RIBE. - Abstract: Tumors are heterogeneous in nature and consist of multiple cell types. Among them, cancer stem-like cells (CSCs) are suggested to be the principal cause of tumor metastasis, resistance and recurrence. Therefore, understanding the behavior of CSCs in direct and indirect irradiations is crucial for clinical radiotherapy. Here, the CSCs and their counterpart non stem-like cancer cells (NSCCs) in human HT1080 fibrosarcoma cell line were sorted and labeled, then the two cell subtypes were mixed together and chosen separately to be irradiated via a proton microbeam. The radiation-induced bystander effect (RIBE) between the CSCs and NSCCs was measured by imaging 53BP1 foci, a widely used indicator for DNA double strand break (DSB). CSCs were found to be less active than NSCCs in both the generation and the response of bystander signals. Moreover, the nitric oxide (NO) scavenger c-PTIO can effectively alleviate the bystander effect in bystander NSCCs but not in bystander CSCs, indicating a difference of the two cell subtypes in NO signal response. To our knowledge, this is the first report shedding light on the RIBE between CSCs and NSCCs, which might contribute to a further understanding of the out-of-field effect in cancer radiotherapy.

  17. Metabolism of radiohafnium in rats and hamsters: a possible analog of plutonium for metabolic studies

    International Nuclear Information System (INIS)

    The metabolism of radiohafnium (175Hf + 181Hf) was studied in male Sprague-Dawley rats and Chinese hamsters for periods of up to 168 days. The results were compared with similar data for 239Pu in the same rat strain. In rats and hamsters the radiohafnium organ distribution was skeleton > skin > muscle > liver at about 7 days postinjection. Retention of radiohafnium and plutonium was similar in plasma and liver, as were the retention time observed for other organs: Absorption of radiohafnium from the gastrointestinal tract of rats was <0.05%. Biochemical studies showed that the radiohafnium was bound mainly to the iron-transport protein, transferrin, in blood plasma and in the liver cytosol of both the rat and the hamster, as has been observed also for plutonium. The metabolic behavior of radiohafnium mimics, to a large extent, that of plutonium, and it is suggested that radiohafnium can serve as a non-α-particle-emitting analog of plutonium for metabolic, biochemical, and selected human investigations

  18. The metabolism of radiohafnium in rats and hamsters: a possible analog of plutonium for metabolic studies

    International Nuclear Information System (INIS)

    The metabolism of radiohafnium (175Hf + 181Hf) was studied in male Sprague-Dawley rats and Chinese hamsters for periods of up to 168 days. The results were compared with similar data for 239Pu in the same rat strain. In rats and hamsters the radiohafnium organ distribution was skeleton greater than skin greater than muscle greater than liver at about 7 days postinjection. Retention of radiohafnium and plutonium was similar in plasma and liver, as were the retention times observed for other organs: Absorption of radiohafnium from the gastrointestinal tract of rats was less than 0.05%. Biochemical studies showed that the radiohafnium was bound mainly to the iron-transport protein, transferrin, in blood plasma and in the liver cytosol of both the rat and the hamster, as has been observed also for plutonium. The metabolic behavior of radiohafnium mimics, to a large extent, that of plutonium, and it is suggested that radiohafnium can serve as a non-alpha-particle-emitting analog of plutonium for metabolic, biochemical, and selected human investigations

  19. Synthesis of human prolactin in Chinese hamster ovary (CHO) cells

    International Nuclear Information System (INIS)

    Three different eukaryotic expression vectors, based on the same selectable gene marker (dhfr), have been used for dhf- CHO cells transfection to rapidly isolate stable cell lines capable of secreting high levels of recombinant human prolactin (rec-hPRL). Two vectors, one codifying a human prolactin (p658-hPRL) and the other a tag-prolactin (p658-tagPRL), contain the complete hepatitis B virus-X (HBV-X) gene coding for a viral transactivator and a sequence derived from the granulocyte-macrophage colony-stimulating factor (GM-CSF) that mediates selective dhfr mRNA degradation. These vectors have the advantage of rapidly obtaining stable cell lines without methotrexate amplification. The highest secretion obtained by these vectors was of approximately 10 μg hPRU106 cells/day. The other vector (pEDdc-hPRL) is based on a dicistronic expression system, containing an internal ribosome entry site isolated from the encephalomyocarditis (EMC) virus. This vector before amplification provided secretion levels at least 10 fold lower than that obtained with the other two vectors. However, after three steps of methotrexate amplification, it provided some clones able to secrete up to 30 μg hPRU106 cells/day. This is the first report describing the production and purification of rec-hPRL from CHO cells, obtaining secretion levels with both vectors higher than those reported so far for this hormone in other eukaryotic systems. CHO-derived rec-hPRL contained approximately 10 % of the glycosylated form, a value that is consistent with results reported for hPRL purified from the pituitary or from transformed murine C-127 cells. CHO-derived rec-hPRL was purified with good yield, obtaining also a good resolution between non-glycosylated and glycosylated prolactin. The latter, when its potency was determined via an in vitro bioassay, presented a 47 % lower bioactivity. A qualitative and quantitative analysis of these forms was also possible thanks to the setting up of a reversed-phase HPLC technique, for the first time applied to this hormone. A pilot production in a hollow fiber bioreactor provided a highly concentrated medium, though with the presence of considerable amounts of hPRL11-199 fragments, apparently the result of a proteolytic process. (author)

  20. Chinese hamster ovary cell lysosomes rapidly exchange contents

    OpenAIRE

    1987-01-01

    We have used cell fusion to address the question of whether macromolecules are rapidly exchanged between lysosomes. Donor cell lysosomes were labeled by the long-term internalization of the fluid- phase pinocytic markers, invertase (sucrase), Lucifer Yellow, FITC- conjugated dextran, or Texas red-conjugated dextran. Recipient cells contained lysosomes swollen by long-term internalization of dilute sucrose or marked by an overnight FITC-dextran uptake. Cells were incubated for 1 or 2 h in mark...

  1. Contamination of genetically engineered Chinese hamster ovary cells.

    Science.gov (United States)

    Burstyn, D G

    1996-01-01

    In late 1988, during production of a recombinant protein for phase I clinical trials, a failure of the cell culture production system occurred due to contamination of the cells by an orbivirus [1]. The incident occurred at Bioferon GmbH & Co, Laupheim, Germany, a joint venture of Biogen, Inc., Cambridge, MA, and Dr. Renstschler Arzneimittel GmbH & Co (Bioferon is currently a wholly owned subsidiary of Rentschler and is now known as Dr. Rentschler Biotechnologie GmbH). The investigation into, and the subsequent response to, the infection can be divided into three stages: Stage I, Investigation and initial response; Stage II, Secondary response; and Stage III: Continuing response.

  2. DNA repair in human xeroderma pigmentosum and chinese hamster cells

    NARCIS (Netherlands)

    Zelle, B.

    1980-01-01

    An important feature of living cells is their capacity to maintain the integrity of their hereditary material, the DNA. DNA can be damaged by a variety of physical and chemical agents, among which ultraviolet radiation (UV), ion1z1ng radiation and chemical carcinogens as 4-nitroquinoline-1-oxide (4N

  3. DNA repair in human xeroderma pigmentosum and Chinese hamster cells

    NARCIS (Netherlands)

    B. Zelle (Bauke)

    1980-01-01

    textabstractAn important feature of living cells is their capacity to maintain the integrity of their hereditary material, the DNA. DNA can be damaged by a variety of physical and chemical agents, among which ultraviolet radiation (UV), ion1z1ng radiation and chemical carcinogens as 4-nitroquinoline

  4. 蓖麻质膜水通道蛋白PIP1.3在仓鼠卵巢细胞中的转运功能%Castor Plasma Membrane Aquaporin (PIP1.3) in Vitro Transprot in Chinese Hamster Ovary

    Institute of Scientific and Technical Information of China (English)

    董乐; 戴聪杰; 王芳; 王云; 朱国立; 谢小宾; 许珊珊; 刘灿阳; 林婷

    2014-01-01

    为研究蓖麻质膜水通道蛋白PIP1.3的转运功能,采用RT-PCR技术扩增基因PIP1.3的全长编码区cDNA序列(861 bp),将该序列亚克隆至真核表达载体pcDNA3.1/Myc-His A,酶切、测序分析表明,重组质粒pcDNA3.1PIP1.3-Myc-His阅读框架正确。将pcDNA3.1PIP1.3-Myc-His和连接氯离子敏感性绿色荧光蛋白突变体(EYFP-H148Q-V163S)的pcDNA3.1Hygro-EY-FP-H148Q-V163S重组质粒稳定共转染至中国仓鼠卵巢(Chinese hamster ovary, CHO)细胞中, RT-PCR和Western blot分析表明, PIP1.3的mRNA和蛋白质在选定CHO细胞克隆中高表达。分别通过荧光法和同位素标记的14C-甘油摄入实验测定该CHO细胞对水分和甘油的通透性,结果表明,该CHO细胞表达的PIP1.3对水分子的转运能力很低,但能选择性转运甘油。%The encoding sequence of plasma membrane aquaporin gene (PIP1.3) in castor (Ricinus communis L.) was ampliifed with RT-PCR and inserted into pcDNA3.1/Myc-His A vector, double enzyme digestion analy-sis and DNA sequencing confirmed that recombination plasmid was successfully constructed. pcD-NA3.1PIP1.3-Myc-His and pcDNA3.1Hygro-EYFP-H148Q-V163S plasmids linking Cl--sensitive EYFP mutant (EYFP-H148Q-V163S) were transfected in CHO cells. The stable transfection of CHO cells was analysis with RT-PCR and Western blot. The results showed that PIP1.3 mRNA and protein were overexpressed in cell line screened. Permeabilities of PIP1.3 expressing CHO cells for water and glycerol were measured respectively by lfuorescence method and carbon labeling experiment. The results showed that permeability of PIP1.3 express-ing CHO cells for water was low, but high for glycerol.

  5. 人β-珠蛋白核基质附着区介导表达载体稳定附着于中国仓鼠卵巢细胞%Expression vector mediated by human β-globin matrix attachment region functions as stable episomes in Chinese hamster ovary cells

    Institute of Scientific and Technical Information of China (English)

    吴向楠; 王天云; 杨瑞; 王俪; 王芳

    2013-01-01

    目的 研究人β-珠蛋白核基质附着区是否能够介导表达载体稳定附着于中国仓鼠卵巢(CHO)细胞.方法 人β-珠蛋白MAR序列克隆到pEGFP-C1构建重组质粒载体pEGFP-MAR,转染CHO细胞,使用Hirt裂解法提取细胞中附着体质粒,CaCI2法转化附着体质粒到宿主大肠杆菌DH5a中,提取质粒,酶切,测序分析.结果 还原质粒双酶切和单酶切结果均与转染前质粒酶切结果一致;测序分析得知还原质粒与转染前质粒中插入片段DNA序列相同.结论 人β-珠蛋白MAR序列重组载体在CHO细胞中以附着体形式被完整还原出来.还原质粒酶切结果和测序结果均与转染前质粒一致.%Objective To study the human β-globin matrix attachment region(MAR) sequence mediated vector whether exist as stable episomes in transfected Chinese hamster ovary(CHO) cells.Methods Recombinant plasmid vector pEGFPMAR was constructed by thrusting the amplified human β-globin MAR sequence into the parental pEGFP-C1.CHO cells were transfected both with pEGFP-C1 and reconstructed vector.Episomal vectors from the stable monoclonal cell lines were extracted by modificated Hirt cracking protocol.Then CaCl2 method was performed to transform episomal vectors into the host bacteria E.coli DH5α,and the plasmid from the transformed E.coli DH5α was extracted.In the end,enzyme digestion identification and sequencing analysis were performed to detect the rescued plasmid and the original plasmid.Results Both double enzyme and single enzyme to completely digested the rescued plasmids and the original plassmid showed the same result.The sequencing analysis showed that the inserted sequence of rescued plasmid was identical to the original DNA sequence.Conclusion Human β-globin MAR characteristic sequence-based vector can be completely rescued from cultured CHO cells.The results of enzyme digestion identification and sequencing analysis are consistent in the rescued plasmids and the original plasmid.

  6. Bystander effects and compartmental stress response to X-ray irradiation in L929 cells.

    Science.gov (United States)

    Temelie, Mihaela; Stroe, Daniela; Petcu, Ileana; Mustaciosu, Cosmin; Moisoi, Nicoleta; Savu, Diana

    2016-08-01

    Bystander effects are indirect consequences of radiation and many other stress factors. They occur in cells that are not directly exposed to these factors, but receive signals from affected cells either by gap junctions or by molecules released in the medium. Characterizing these effects and deciphering the underlying mechanisms involved in radiation-induced bystander effects are relevant for cancer radiotherapy and radioprotection. At doses of X-ray radiation 0.5 and 1 Gy, we detected bystander effects as increased numbers of micronuclei shortly after the treatment, through medium transfer and by co-cultures. Interestingly, bystander cells did not exhibit long-term adverse changes in viability. Evaluation of several compartmental stress markers (CHOP, BiP, mtHsp60, cytHsp70) by qRT-PCR did not reveal expression changes at transcriptional level. We investigated the involvement of ROS and NO in this process by addition of specific scavengers of these molecules, DMSO or c-PTIO in the transferred medium. This approach proved that ROS but not NO is involved in the induction of lesions in the acceptor cells. These results indicate that L929 cells are susceptible to stress effects of radiation-induced bystander signaling. PMID:27025606

  7. Proteome analysis of proliferative response of bystander cells adjacent to cells exposed to ionizing radiation.

    Science.gov (United States)

    Gerashchenko, Bogdan I; Yamagata, Akira; Oofusa, Ken; Yoshizato, Katsutoshi; de Toledo, Sonia M; Howell, Roger W

    2007-06-01

    Recently (Cytometry 2003, 56A, 71-80), we reported that direct cell-to-cell contact is required for stimulating proliferation of bystander rat liver cells (WB-F344) cocultured with irradiated cells, and neither functional gap junction intercellular communication nor long-range extracellular factors appear to be involved in this proliferative bystander response (PBR). The molecular basis for this response is unknown. Confluent monolayers of WB-F344 cells were exposed to 5-Gray (Gy) of gamma-rays. Irradiated cells were mixed with unirradiated cells and co-cultured for 24 h. Cells were harvested and protein expression was examined using 2-DE. Protein expression was also determined in cultures of unirradiated and 5-Gy irradiated cells. Proteins were identified by MS. Nucleophosmin (NPM)-1, a multifunctional nucleolar protein, was more highly expressed in bystander cells than in either unirradiated or 5-Gy irradiated cells. Enolase-alpha, a glycolytic enzyme, was present in acidic and basic variants in unirradiated cells. In bystander and 5-Gy irradiated cells, the basic variant was weakly expressed, whereas the acidic variant was overwhelmingly present. These data indicate that the presence of irradiated cells can affect NPM-1 and enolase-alpha in adjacent bystander cells. These proteins appear to participate in molecular events related to the PBR and suggest that this response may involve cellular defense, proliferation, and metabolism.

  8. Booze, Bars, and Bystander Behavior: People Who Consumed Alcohol Help Faster in the Presence of Others.

    Science.gov (United States)

    van Bommel, Marco; van Prooijen, Jan-Willem; Elffers, Henk; Van Lange, Paul A M

    2016-01-01

    People help each other less often and less quickly when bystanders are present. In this paper, we propose that alcohol consumption could attenuate or reverse this so-called bystander effect. Alcohol impairs people cognitively and perceptually, leading them to think less about the presence of others and behave less inhibited. Moreover, alcohol makes people more prone to see the benefits of helping and not the costs. To provide an initial test of these lines of reasoning, we invited visitors of bars in Amsterdam to join our study at a secluded spot at the bar. We manipulated bystander presence, and at the end of the study, we measured alcohol consumption. When participants took their seats, the experimenter dropped some items. We measured how many items were picked up and how quickly participants engaged in helping. Results revealed that alcohol did not influence the bystander effect in terms of the amount of help given. But importantly, it did influence the bystander effect in terms of response times: people who consumed alcohol actually came to aid faster in the presence of others.

  9. Booze, Bars, and Bystander Behavior: People who Consumed Alcohol Help Faster in the Presence of Others.

    Directory of Open Access Journals (Sweden)

    Marco eVan Bommel

    2016-02-01

    Full Text Available People help each other less often and less quickly when bystanders are present. In this paper, we propose that alcohol consumption could attenuate or reverse this so-called bystander effect. Alcohol impairs people cognitively and perceptually, leading them to think less about the presence of others and behave less inhibited. Moreover, alcohol makes people more prone to see the benefits of helping and not the costs. To provide an initial test of these lines of reasoning, we invited visitors of bars in Amsterdam to join our study at a secluded spot at the bar. We manipulated bystander presence, and at the end of the study, we measured alcohol consumption. When participants took their seats, the experimenter dropped some items. We measured how many items were picked up and how quickly participants engaged in helping. Results revealed that alcohol did not influence the bystander effect in terms of the amount of help given. But importantly, it did influence the bystander effect in terms of response times: People who consumed alcohol actually came to aid faster in the presence of others.

  10. Caspase-3-independent pathways proceeding in bystander effect of HSV-tk/GCV system

    Science.gov (United States)

    Lin, Juqiang; Ma, Yan; Zeng, Shaoqun; Zhang, Zhihong

    2008-02-01

    HSV-tk/GCV system, which is the virus-directed enzyme/prodrug therapy of herpes simplex virus (HSV) thymidine kinase (tk) gene / the anti-viral reagent ganciclovir (GCV), is one of the promising approaches in the rapidly growing area of gene therapy. As gene therapy of cancer such as suicide gene therapy has entered the clinic, another therapy effect which is called 'bystander effect' was reported. Bystander effect can lead to killing of non-transduced tumor cells in the immediate vicinity of GCV-treated HSV-TK-positive cells. Now the magnitude of 'bystander effect' is an essential factor for this anti-tumor approach in vivo. However, the mechanism which HSV-tk/ACV brings "bystander effect" is poorly understood. In this study, we monitor the activation of caspase-3 in HSV-tk/GCV system by a FRET probe CD3, a FRET-based indicator for activity of caspase3, which is composed of an enhanced cyan fluorescent protein, a caspase-sensitive linker, and a red fluorescent protein from Discosoma with efficient maturation property. Through application of CD3 we have visualized the activation of caspase-3 in tk gene positive human adenoid cystic carcinoma (ACC-M) cells but not in bystander effect of HSV-tk/GCV system induced by GCV. This finding provides needed information for understanding the mechanisms by which suicide gene approaches actually kill cancer cells, and may prove to be helpful for the clinical treatment of cancers.

  11. Bystander effect studies using heavy-ion microbeam

    International Nuclear Information System (INIS)

    We have established a single cell irradiation system, which allows selected cells to be individually hit with defined number of heavy charged particles, using a collimated heavy-ion microbeam apparatus at JAEA-Takasaki. This system has been developed to study radiobiological processes in hit cells and bystander cells exposed to low dose and low dose-rate high-LET radiations, in ways that cannot be achieved using conventional broad-field exposures. Individual cultured cells grown in special dishes were irradiated in the atmosphere with a single or defined numbers of 18.3 MeV/amu 12C, 13.0 or 17.5 MeV/amu 20Ne, and 11.5 MeV/amu 40Ar ions. Targeting and irradiation of the cells were performed automatically according to the positional data of the target cells microscopically obtained before irradiation. The actual number of particle tracks that pass through target cells was detected with prompt etching of the bottom of the cell dish made of ion track detector TNF-1 (modified CR-39). (author)

  12. Bioactivation of diethylstilbestrol by the Syrian hamster kidney

    Energy Technology Data Exchange (ETDEWEB)

    Adams, S.P.

    1987-01-01

    Male Syrian golden hamsters chronically exposed to diethylstilbestrol (DES) develop renal adenocarcinomas with an incidence approaching 100%. The ability of the hamster kidney to bioactivate DES was assessed using hamster kidney slices. The male hamster renal cortex has a 2- to 5-fold greater capacity to irreversibly bind ({sup 3}H)DES as compared with female hamster renal cortex and with male hamster renal medulla. Incubation of the tissue under anaerobic conditions inhibited the metabolism and irreversible binding of ({sup 3}H)DES. Gel electrophoresis analysis of covalently modified proteins revealed several radioactive peaks indicating that specific adduct formation had occurred. The cytochrome P-450 inhibitors SKF 525-A, metyrapone, carbon monoxide, butylated hydroxytoluene, and dicumarol decreased the irreversible binding of ({sup 3}H)DES to renal cortical protein by 38 to 72%.

  13. Sorority Women's and Fraternity Men's Rape Myth Acceptance and Bystander Intervention Attitudes

    Science.gov (United States)

    Bannon, R. Sean; Brosi, Matthew W.; Foubert, John D.

    2013-01-01

    Sorority women and fraternity men are more likely than other students to be survivors and perpetrators of sexual assault, respectively. The present study examined sorority and fraternity members' rape myth acceptance, bystander efficacy, and bystander willingness to help in potential sexual assault situations. Sorority women were more…

  14. A Longitudinal Study of the Associations between Moral Disengagement and Active Defending versus Passive Bystanding during Bullying Situations

    Science.gov (United States)

    Doramajian, Caroline; Bukowski, William M.

    2015-01-01

    This study investigated the prospective association between moral disengagement and bystander behaviors in bullying situations, including both defending and passive bystanding. A diverse sample of Canadian school children (N = 130; 68 boys and 62 girls; mean age = 11.36 years) participated in a three-wave longitudinal study over a 4-month period.…

  15. Radiation induced bystander signals are independent of DNA damage and DNA repair capacity of the irradiated cells

    International Nuclear Information System (INIS)

    Evidence is accumulating that irradiated cells produce signals, which interact with non-exposed cells in the same population. Here, we analysed the mechanism for bystander signal arising in wild-type CHO cells and repair deficient varients, focussing on the relationship between DNA repair capacity and bystander signal arising in irradiated cells. In order to investigate the bystander effect, we carried out medium transfer experiments after X-irradiation where micronuclei were scored in non-targeted DSB repair deficient xrs5 cells. When conditioned medium from irradiated cells was transferred to unirradiated xrs5 cells, the level of induction was independent of whether the medium came from irradiated wild-type, ssb or dsb repair deficient cells. This result suggests that the activation of a bystander signal is independent of the DNA repair capacity of the irradiated cells. Also, pre-treatment of the irradiated cells with 0.5% DMSO, which suppresses micronuclei induction in CHO but not in xrs5 cells, suppressed bystander effects completely in both conditioned media, suggesting that DMSO is effective for suppression of bystander signal arising independently of DNA damage in irradiated cells. Overall the work presented here adds to the understanding that it is the repair phenotype of the cells receiving bystander signals, which determines overall response rather than that of the cell producing the bystander signal

  16. Molecular and immunological characterization of the first allergenic lipocalin in hamster: the major allergen from Siberian hamster (Phodopus sungorus).

    Science.gov (United States)

    Torres, José Alberto; de Las Heras, Manuel; Maroto, Aroa Sanz; Vivanco, Fernando; Sastre, Joaquín; Pastor-Vargas, Carlos

    2014-08-22

    The most frequent pet allergy is to cat and dog, but in recent years, it has become increasingly popular to have other pets, and the risk of exposure to new allergens is more prevalent. The list of new pets includes hamsters, and one of the most popular hamsters is the Siberian hamster (Phodopus sungorus). The aim of this study was the characterization and cloning of the major allergen from this hamster. The study of its allergenicity and cross-reactivity could improve the specific diagnosis and treatment for hamster-allergic patients. Thirteen Siberian hamster-allergic patients were recruited at the outpatient clinic. Protein extracts were prepared from the hair, urine, and salivary glands of four hamster species (European, golden, Siberian, and Roborovski). IgE-binding proteins were detected by immunoblotting and identified by mass spectrometry. The recombinant protein was produced in Escherichia coli and then purified by metal chelate affinity chromatography. The allergenic properties of the recombinant protein were tested by ELISA and immunoblotting, and biological activity was tested according to capacity for basophil activation. Three IgE-binding proteins were identified in extracts obtained from Siberian hamster hair, urine, and salivary glands. All proteins corresponded to the same protein, which was identified as a lipocalin. This lipocalin had no cross-reactivity with common and golden hamsters. The recombinant allergen was cloned and purified, showing similar IgE reactivity in vitro to Siberian hamster protein extracts. Also, the recombinant allergen was capable of producing biological activation in vivo. The major Siberian hamster allergen was cloned, and allergenic properties were characterized, providing a new tool for specific diagnosis of allergy to Siberian hamster.

  17. The Influence of Social Norms on Advancement Through Bystander Stages for Preventing Interpersonal Violence.

    Science.gov (United States)

    Deitch-Stackhouse, Jacqueline; Kenneavy, Kristin; Thayer, Richard; Berkowitz, Alan; Mascari, Janine

    2015-10-01

    This research evaluates the impact of social norms on the advancement through the bystander stages toward prosocial (active) intervention in interpersonal violence (IPV): emotional abuse, physical violence, controlling behavior, sexual violence, and stalking. The influence of social norms on bystander behavior across stages and types of violence varies. Accurate social norms perceptions are associated with routine intervention, although social norms misperceptions are not always a strong deterrent to intervention. Interpretation of a violent situation as problematic predicts increased willingness to intervene. Implications for the development of social norms antiviolence campaigns and strategies for reducing barriers to prosocial intervention are discussed. PMID:26175519

  18. Optional exon in the 5'-untranslated region of 3-hydroxy-3-methylglutaryl coenzyme A synthase gene: conserved sequence and splicing pattern in humans and hamsters

    International Nuclear Information System (INIS)

    3-Hydroxy-3-methylglutaryl coenzyme A synthase (hydroxymethylglutaryl-CoA synthase, EC 4.1.3.5) is a negatively regulated enzyme in the synthetic pathway for cholesterol, isopentenyl tRNA, and other isoprenoids. The 5'-untranslated region of the mRNA for Chinese hamster hydroxymethylglutaryl-CoA synthase contains an optional exon of 59 nucleotides located 10 nucleotides upstream of the translation start site. About 50% of the mRNAs contain this exon, and the other 50% lack it owing to differential intron splicing. The authors show that the two transcripts are found in similar ratios in multiple tissues of the Syrian hamster, including the brain. The relative amounts of the two transcripts in brain and liver are constant from day 0 to day 75 of life. A similar alternative splicing pattern for hydroxymethylglutaryl-CoA synthase was observed in three human tissues: cultured fibroblasts, fetal adrenal gland, and fetal liver. A cDNA for human synthase had 90% homology to the hamster sequence in the region corresponding to the optional exon. This sequence contains a 20 out of 26 nucleotide match with the sequence immediately upstream of the initiator AUG codon in the mRNA for hamster hydroxymethylglutaryl-CoA reductase, the enzyme that follows the synthase in the isoprenoid biosynthetic pathway. These findings raise the possibility that the optional exon plays an important, conserved functional role in humans and hamsters

  19. The different radiation response and radiation-induced bystander effects in colorectal carcinoma cells differing in p53 status

    Energy Technology Data Exchange (ETDEWEB)

    Widel, Maria, E-mail: maria.widel@polsl.pl [Biosystems Group, Institute of Automatic Control, Silesian University of Technology, 16 Akademicka Street, 44-100 Gliwice (Poland); Lalik, Anna; Krzywon, Aleksandra [Biosystems Group, Institute of Automatic Control, Silesian University of Technology, 16 Akademicka Street, 44-100 Gliwice (Poland); Poleszczuk, Jan [College of Inter-faculty Individual Studies in Mathematics and Natural Sciences, University of Warsaw, 93 Zwirki i Wigury Street, 02-089 Warsaw (Poland); Department of Integrated Mathematical Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida (United States); Fujarewicz, Krzysztof; Rzeszowska-Wolny, Joanna [Biosystems Group, Institute of Automatic Control, Silesian University of Technology, 16 Akademicka Street, 44-100 Gliwice (Poland)

    2015-08-15

    Highlights: • We tested radiation response and bystander effect on HCT116p53+/+ and p53−/− cells. • The p53+/+ cells developed premature senescence in exposed and bystander neighbors. • Directly exposed and bystander p53−/− cells died profoundly through apoptosis. • Interleukins 6 and 8 were differently generated by both cell lines. • NFκB path was activated mainly in p53+/+ hit cells, in p53 −/− in bystanders only. - Abstract: Radiation-induced bystander effect, appearing as different biological changes in cells that are not directly exposed to ionizing radiation but are under the influence of molecular signals secreted by irradiated neighbors, have recently attracted considerable interest due to their possible implication for radiotherapy. However, various cells present diverse radiosensitivity and bystander responses that depend, inter alia, on genetic status including TP53, the gene controlling the cell cycle, DNA repair and apoptosis. Here we compared the ionizing radiation and bystander responses of human colorectal carcinoma HCT116 cells with wild type or knockout TP53 using a transwell co-culture system. The viability of exposed to X-rays (0–8 Gy) and bystander cells of both lines showed a roughly comparable decline with increasing dose. The frequency of micronuclei was also comparable at lower doses but at higher increased considerably, especially in bystander TP53-/- cells. Moreover, the TP53-/- cells showed a significantly elevated frequency of apoptosis, while TP53+/+ counterparts expressed high level of senescence. The cross-matched experiments where irradiated cells of one line were co-cultured with non-irradiated cells of opposite line show that both cell lines were also able to induce bystander effects in their counterparts, however different endpoints revealed with different strength. Potential mediators of bystander effects, IL-6 and IL-8, were also generated differently in both lines. The knockout cells secreted IL-6 at

  20. The different radiation response and radiation-induced bystander effects in colorectal carcinoma cells differing in p53 status

    International Nuclear Information System (INIS)

    Highlights: • We tested radiation response and bystander effect on HCT116p53+/+ and p53−/− cells. • The p53+/+ cells developed premature senescence in exposed and bystander neighbors. • Directly exposed and bystander p53−/− cells died profoundly through apoptosis. • Interleukins 6 and 8 were differently generated by both cell lines. • NFκB path was activated mainly in p53+/+ hit cells, in p53 −/− in bystanders only. - Abstract: Radiation-induced bystander effect, appearing as different biological changes in cells that are not directly exposed to ionizing radiation but are under the influence of molecular signals secreted by irradiated neighbors, have recently attracted considerable interest due to their possible implication for radiotherapy. However, various cells present diverse radiosensitivity and bystander responses that depend, inter alia, on genetic status including TP53, the gene controlling the cell cycle, DNA repair and apoptosis. Here we compared the ionizing radiation and bystander responses of human colorectal carcinoma HCT116 cells with wild type or knockout TP53 using a transwell co-culture system. The viability of exposed to X-rays (0–8 Gy) and bystander cells of both lines showed a roughly comparable decline with increasing dose. The frequency of micronuclei was also comparable at lower doses but at higher increased considerably, especially in bystander TP53-/- cells. Moreover, the TP53-/- cells showed a significantly elevated frequency of apoptosis, while TP53+/+ counterparts expressed high level of senescence. The cross-matched experiments where irradiated cells of one line were co-cultured with non-irradiated cells of opposite line show that both cell lines were also able to induce bystander effects in their counterparts, however different endpoints revealed with different strength. Potential mediators of bystander effects, IL-6 and IL-8, were also generated differently in both lines. The knockout cells secreted IL-6 at

  1. Radiation-induced anorexia in Syrian hamsters

    International Nuclear Information System (INIS)

    The recovery of Syrian hamsters after split dose application (interval 11 days) was studied on the basis of the weight response and of food uptake. Two periods of weight loss and anorexia can be distinguished, an early one immediately after irradiation and a secondary one 6-10 days later. The secondary response is a function of the radiation dose and allows to distinguish survivors from non-survivors, since it is much more pronounced and longerlasting in the latter than in the former. The first response appears not to be influenced by a previous conditioning irradiation. (orig.)

  2. Radiation-induced anorexia in Syrian hamsters

    Energy Technology Data Exchange (ETDEWEB)

    Kindt, A.; Sattler, E.L.; Schraub, A.

    1980-10-01

    The recovery of Syrian hamsters after split dose application (interval 11 days) was studied on the basis of the weight response and of food uptake. Two periods of weight loss and anorexia can be distinguished, an early one immediately after irradiation and a secondary one 6-10 days later. The secondary response is a function of the radiation dose and allows to distinguish survivors from non-survivors, since it is much more pronounced and longerlasting in the latter than in the former. The first response appears not to be influenced by a previous conditioning irradiation.

  3. Circadian rhythms of photorefractory siberian hamsters remain responsive to melatonin.

    Science.gov (United States)

    Butler, Matthew P; Paul, Matthew J; Turner, Kevin W; Park, Jin Ho; Driscoll, Joseph R; Kriegsfeld, Lance J; Zucker, Irving

    2008-04-01

    Short day lengths increase the duration of nocturnal melatonin (Mel) secretion, which induces the winter phenotype in Siberian hamsters. After several months of continued exposure to short days, hamsters spontaneously revert to the spring-summer phenotype. This transition has been attributed to the development of refractoriness of Mel-binding tissues, including the suprachiasmatic nucleus (SCN), to long-duration Mel signals. The SCN of Siberian hamsters is required for the seasonal response to winter-like Mel signals, and becomes refractory to previously effective long-duration Mel signals restricted to this area. Acute Mel treatment phase shifts circadian locomotor rhythms of photosensitive Siberian hamsters, presumably by affecting circadian oscillators in the SCN. We tested whether seasonal refractoriness of the SCN to long-duration Mel signals also renders the circadian system of Siberian hamsters unresponsive to Mel. Males manifesting free-running circadian rhythms in constant dim red light were injected with Mel or vehicle for 5 days on a 23.5-h T-cycle beginning at circadian time 10. Mel injections caused significantly larger phase advances in activity onset than did the saline vehicle, but the magnitude of phase shifts to Mel did not differ between photorefractory and photosensitive hamsters. Similarly, when entrained to a 16-h light/8-h dark photocycle, photorefractory and photosensitive hamsters did not differ in their response to Mel injected 4 h before the onset of the dark phase. Activity onset in Mel-injected hamsters was masked by light but was revealed to be significantly earlier than in vehicle-injected hamsters upon transfer to constant dim red light. The acute effects of melatonin on circadian behavioral rhythms are preserved in photorefractory hamsters.

  4. Bystander Intervention, Bullying, and Victimization: A Multilevel Analysis of New Zealand High Schools

    Science.gov (United States)

    Denny, Simon; Peterson, Elizabeth R.; Stuart, Jaimee; Utter, Jennifer; Bullen, Pat; Fleming, Theresa; Ameratunga, Shanthi; Clark, Terryann; Milfont, Taciano

    2015-01-01

    This study examines the association between schools and student bullying behaviors and victimization among a nationally representative sample (N = 9,107) of New Zealand high school students. In particular, the study sought to explore the role of characteristics of schools and school culture with respect to bystander behavior, while controlling for…

  5. Tell the Teacher or Tell the Bully Off: Children's Strategy Production for Bystanders to Bullying

    Science.gov (United States)

    Rock, Patrick F.; Baird, Jodie A.

    2012-01-01

    Although children's reticence to intervene as bystanders to bullying is well established, the reasons for their inaction remain unclear. One possibility is that they are incapable of generating appropriate response strategies in these situations. This study examined the number and type of strategies children (N = 104, 6-11 years) could generate…

  6. Culture of three-dimensional tissue model and its application in bystander-effect research

    International Nuclear Information System (INIS)

    Compared with the cultured monolayer (2D) cells, three-dimensional (3D) tissue could be more similar to the environment in vivo including the physical support, chemical factors, cell-cell and cell-matrix interaction and so on. With the development of three-dimensional cell culture techniques (TDCC), 3D tissue is widely used in the areas of bystander effect research. This review focuses on introducing the TDCC method and its application in bystander-effect research. First, the development process of 3D tissue culture method was introduced. Secondly, the induction of radiation induced bystander effects both in 2D cell and 3D tissue and its mechanisms were reviewed. Finally, because heavy ion (carbon ion beam) has been developed as a useful tool to cure solid cancer, and the 3D tissue model is an ideal material to study the damages on body after being irradiated and to understand the underlying mechanisms, future study about heavy ion radiation inducing bystander effect in 3D tissue was discussed. (authors)

  7. The effects of direct irradiation and bystander medium on EPC and CHSE cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Olwell, P.; Mothersill, C.; Seymour, C.; Cottell, D.C.; Lyng, F.M. [Dublin Institute of Technology, Radiation and Environmental Science Centre, Dublin (Ireland)

    2004-07-01

    The majority of studies involving the effects of direct radiation on cell lines use mammalian cells and the effects of bystander medium have all exclusively dealt with mammalian cells. There is increasing evidence that the effects of radiation differ in severity between different species. Two fish cell lines were irradiated in order to establish the radiosensitivity of fish cells. These cell lines, fibroblast-like CHSE 214 and epithelial-like EPC, were irradiated and compared to non-irradiated controls using three investigative parameters; lactate dehydrogenase (LDH) release, surface morphology and reproductive integrity. The same cell lines were also incubated with medium from irradiated cells (bystander medium) and compared to controls using the same methods as were used for directly irradiated cell lines. LDH is released when the plasma membrane of a cell is ruptured indicating non-lethal damage. Both cell lines were shown to exhibit less LDH release following direct radiation and exposure to bystander medium than mammalian cell lines of the same cell type. The surface of CHSE 214 cells showed an increase in surface features following direct radiation and exposure to bystander medium. The surface of EPC cells showed no significant surface differences following irradiation. Clonogenic studies of both cell lines, which detect effects in the cloning ability of cells, showed results similar to those seen in mammalian studies. The results are discussed and compared to studies using mammalian cells. (author)

  8. Participation in High School Sports and Bystander Intentions, Efficacy to Intervene, and Rape Myth Beliefs.

    Science.gov (United States)

    McMahon, Sarah

    2015-10-01

    Debate exists as to whether male athletes are more prone to commit acts of sexual violence and maintain problematic attitudes about sexual assault. To contribute to the literature on this relationship, this study posed the following research questions: (1) Do those students who participated in high school sports and those who did not differ significantly in their attitudes about sexual violence and willingness to intervene as a bystander? Do these differ among types of rape myths and bystander intervention situations? (2) Within a group of athletes, are there significant differences by gender or type of sport (contact sport vs. non-contact?) To answer these questions, surveys were analyzed with a sample of recent high school graduates the summer before entering college (N = 3,588). Results indicate that there were only minor differences between those students who participated in high school varsity sports and those who did not. Students who participated in sports had greater acceptance of three out of five types of rape myths, and less willingness to intervene with perpetrators after an assault; however, the effect sizes were small. There were no significant differences for bystander efficacy. The interaction between sport and gender was significant, but contact sport was not. The findings suggest that there may be aspects of male athletic participation in sports that needs to be addressed, yet there also exists the potential for engaging athletes as leaders who can act as prosocial bystanders. PMID:25392384

  9. BYSTANDERS, ADAPTIVE RESPONSES AND GENOMIC INSTABILITY - POTENTIAL MODIFIERS OF LOW-DOSE CANCER RESPONSES.

    Science.gov (United States)

    Bystanders, Adaptive Responses and Genomic Instability -Potential Modifiers ofLow-DoseCancer Responses.There has been a concerted effort in the field of radiation biology to better understand cellularresponses that could have an impact on the estin1ation of cancer...

  10. Development of a mathematical model to study the radiation-induced bystander effect

    Energy Technology Data Exchange (ETDEWEB)

    Meireles, Sincler P. de; Santos, Adriano M.; Grynberg, Suely Epsztein, E-mail: spm@cdtn.b, E-mail: amsantos@cdtn.b, E-mail: seg@cdtn.b [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil); Nunes, Maria Eugenia S., E-mail: mariaeugenia@iceb.ufop.b [Universidade Federal de Ouro Preto (UFOP), MG (Brazil)

    2011-07-01

    Living organisms are composed of millions of cells that together perform tasks of great complexity. Although every cell has an internal structure that obeys the laws of chemistry and biochemistry, it is the interactions between cells that generate a range of different phenomena. Until the 1990s it was believed that the DNA was the single molecule affected by radiation, the so-called theory of the single target. But some observations began to challenge this theory; in 1992 the bystander effect was described by Nagasawa and Little. This effect is responsible for a series of responses such as death, chromosomal instability or other abnormalities that occur in non-irradiated cells that came into contact with irradiated cells or medium from irradiated cells. Understanding the bystander effect may have important consequences for therapy and studies of low-dose risk. In this work, we have developed a computational model to study the bystander effect. This computational model is a two-dimensional cellular automata, consisting of two overlapping networks, where the first represents the cell culture, and the second one, the medium in which cells are embedded. The computational model allows the establishment of curves to describe the behavior of the effect for different levels of signals released in the irradiated medium by the irradiated cells or by the bystander cells when a second order effect is considered. The percentage of cell survival obtained from the mathematical model showed to be in good agreement with experimental data available in the literature. (author)

  11. Using a Multimedia Social Marketing Campaign to Increase Active Bystanders on the College Campus

    Science.gov (United States)

    Potter, Sharyn J.

    2012-01-01

    Objective: To evaluate the campus-wide administration of the Know Your Power bystander-oriented social marketing campaign. Participants: Undergraduate students at a public college were invited to participate in a public awareness survey before and after the 6-week campaign administration in February and March 2009. Methods: Pretest and posttests…

  12. Participant Roles in Bullying: How Can Peer Bystanders Be Utilized in Interventions?

    Science.gov (United States)

    Salmivalli, Christina

    2014-01-01

    This article provides a view of school bullying as a group phenomenon and practical implications stemming from this approach. The motivation for bullying perpetration often relates to one's social standing in the group. Peer bystanders are typically present when bullying takes place, often providing the perpetrators with social rewards. The…

  13. A Meta-Analysis of School-Based Bullying Prevention Programs' Effects on Bystander Intervention Behavior

    Science.gov (United States)

    Polanin, Joshua R.; Espelage, Dorothy L.; Pigott, Therese D.

    2012-01-01

    This meta-analysis synthesized bullying prevention programs' effectiveness at increasing bystander intervention in bullying situations. Evidence from 12 school-based programs, involving 12,874 students, indicated that overall the programs were successful (Hedges's g = 0.20, 95% confidence interval [CI] = 0.11 to 0.29, p = 0.001), with larger…

  14. Using Role-Taking and Behavioral Mimicking in Games to Increase Awareness on the Bystander Effect

    DEFF Research Database (Denmark)

    Soegaard Andersen, Josephine; Schoenau-Fog, Henrik

    2015-01-01

    This study presents a concept on how a serious game might raise awareness of the bystander effect by using elements of game theory as well as a few psychological terms. The paper summarizes the theories and concludes with the description of a concept, which is a third person role playing game...

  15. The Role of DNA Methylation Changes in Radiation-Induced Bystander Effects in cranial irradiated Mice

    Science.gov (United States)

    Zhang, Meng; Sun, Yeqing; Xue, Bei; Wang, Xinwen; Wang, Jiawen

    2016-07-01

    Heavy-ion radiation could lead to bystander effect in neighboring non-hit cells by signals released from directly-irradiated cells. The exact mechanisms of radiation-induced bystander effect in distant organ remain obscure, yet accumulating evidence points to the role of DNA methylation changes in bystander effect. To identify the molecular mechanism that underlies bystander effects of heavy-ion radiation, the male Balb/c and C57BL mice were cranial exposed to 40, 200, 2000mGy dose of carbon heavy-ion radiation, while the rest of the animal body was shielded. The γH2AX foci as the DNA damage biomarker in directly irradiation organ ear and the distant organ liver were detected on 0, 1, 2, 6, 12 and 24h after radiation, respectively. Methylation-sensitive amplifcation polymorphism (MSAP) was used to monitor the level of polymorphic genomic DNA methylation changed with dose and time effects. The results show that cranial irradiated mice could induce the γH2AX foci and genomic DNA methylation changes significantly in both the directly irradiation organ ear and the distant organ liver. The percent of DNA methylation changes were time-dependent and tissue-specific. Demethylation polymorphism rate were highest separately at 1 h in 200 mGy and 6 h in 2000 mGy after irradiation in ear. The global DNA methylation changes tended to occur in the CG sites. We also found that the numbers of γH2AX foci and the genomic methylation changes of heavy-ion radiation-induced bystander effect in liver could be obvious 1 h after radiation and achieved the maximum at 6 h, while the changes could recover gradually at 12 h. The results suggest that mice head exposed to heavy-ion radiation can induce damage and methylation pattern changed in both directly radiation organ ear and distant organ liver. Moreover, our findings are important to understand the molecular mechanism of radiation induced bystander effects in vivo. Keywords: Heavy-ion radiation; Bystander effect; DNA methylation; γH2

  16. Bystander Motivation in Bullying Incidents: To Intervene or Not to Intervene?

    Directory of Open Access Journals (Sweden)

    Robert Thornberg

    2012-08-01

    Full Text Available Introduction: This research sought to extend knowledge about bystanders in bullying situations with a focus on the motivations that lead them to different responses. The 2 primary goals of this study were to investigate the reasons for children’s decisions to help or not to help a victim when witnessing bullying, and to generate a grounded theory (or conceptual framework of bystander motivation in bullying situations.Methods: Thirty students ranging in age from 9 to 15 years (M=11.9; SD=1.7 from an elementary and middle school in the southeastern United States participated in this study. Open- ended, semistructured interviews were used, and sessions ranged from 30 to 45 minutes. We conducted qualitative methodology and analyses to gain an in-depth understanding of children’s perspectives and concerns when witnessing bullying.Results: A key finding was a conceptual framework of bystander motivation to intervene in bullying situations suggesting that deciding whether to help or not help the victim in a bullying situation depends on how bystanders define and evaluate the situation, the social context, and their own agency. Qualitative analysis revealed 5 themes related to bystander motives and included: interpretation of harm in the bullying situation, emotional reactions, social evaluating, moral evaluating, and intervention self-efficacy.Conclusion: Given the themes that emerged surrounding bystanders’ motives to intervene or abstain from intervening, respondents reported 3 key elements that need to be confirmed in future research and that may have implications for future work on bullying prevention. These included: first, the potential importance of clear communication to children that adults expect bystanders to intervene when witnessing bullying; second, the potential of direct education about how bystanders can interveneto increase children’s self-efficacy as defenders of those who are victims of bullying; and third, the assumption

  17. Study on the immuno-effects and influencing factors of Chinese Hamster Ovary (CHO) cell hepatitis B vaccine among adults, under different dosages%不同剂量国产重组酵母乙型肝炎疫苗成年人免疫效果及影响因素研究

    Institute of Scientific and Technical Information of China (English)

    张卫; 马建新; 张海燕; 王晨; 杨鹏; 李辉; 孙美平; 贺雄; 庞星火; 林长缨; 韩莉莉; 李立秋; 高培; 林晖; 龚晓红; 黄芳; 唐雅清

    2010-01-01

    Objective To evaluate the immuno-effect and related influencing factors on 10 μg and 20 μg Chinese hamster ovary (CHO) cell hepatitis B vaccine, using the randomized double-blind controlled trials in adult population. Methods A total of 642 adults aged 18-45 years old, non-vaccinated against hepatitis B, and negative on five blood indicators for hepatitis B, were selected as the study objects from four districts in Beijing. The study objects were randomly divided into two groups, and then accepted 10 tg and 20 μg recombinant CHO hepatitis B vaccination by 0-1-6 month schedule. Influencing factors were investigated by means of questionnaire. Blood samples were collected one month after the third dose of vaccination. Anti-HBs level was detected by Abott chemiluminescence detection method. For the anti-HBs negative person, fluorescent quantitative PCR method was used to find out if the person had been infected with HBV. Logistic regression analysis was used to find out the influencing factors of anti-HBs seroconversion on every studied subject. Results The anti-HBs seroconversion rates on 10 μg and 20 μg dose groups were 88.8%(95%CI: 85.4%-92.2%) and 95.3%(95%CI: 93.0%-97.6%)respectively. Taking the anti-HBs level<100 mIU/ml as the low/non-response standard, the low response and non-response rates were 34.3% and 17.4% respectively. The geometric mean titers(GMT)of anti-HBs were 173.42 mIU/ml for the 10 μg dose group and 588.51 mIU/ml for the 20 μg dose group. Data from the Multivariate analysis showed that: diabetes, spouses infected with hepatitis B virus and old age were unfavorable factors for anti-HBs Seroconversion. 20 μg dose of the vaccine was conducive to seroconversion.Conclusion 20 μg CHO hepatitis B vaccine seemed better than 10 μg CHO hepatitis B vaccine while many factors need to be taken into account for evaluation on hepatitis B vaccines.%目的 通过随机双盲对照试验,评价10μg和20μg国产重组酵母(CHO)乙型肝炎(乙肝)疫

  18. The relevance of radiation induced bystander effects for low dose radiation carcinogenic risk

    International Nuclear Information System (INIS)

    Full text: Where epidemiology studies lack the ability to prescribe radiation doses, customise sample sizes and replicate findings, radiobiology experiments provide greater flexibility to control experimental conditions. This control simplifies the process of answering questions concerning carcinogenic risk after low dose radiation exposures. However, the flexibility requires critical evaluation of radiobiology findings to ensure that the right questions are being asked, the experimental conditions are relevant to human exposure scenarios and that the data are cautiously interpreted in the context of the experimental model. In particular, low dose radiobiology phenomena such as adaptive responses, genomic instability and bystander effects need to be investigated thoroughly, with continual reference to the way these phenomena might occur in the real world. Low dose radiation induced bystander effects are of interest since their occurrence in vivo could complicate the shape of the radiation dose-response curve in the low dose range for a number of biological endpoints with subsequent effects on radiation-induced cancer risk. Conversely, radiation-induced abscopal effects implicate biological consequences of radiation exposure outside irradiated volumes, and complicate the notion of effective dose calculations. Achieving a consensus on the boundaries that distinguish the radiobiology phenomena of bystander and abscopal effects will aid progress towards understanding their relevance to in vivo radiation exposures. A proposed framework for discussing bystander effects and abscopal effects in their appropriate context will be outlined, with a discussion on the future investigation of radiation-induced bystander effects. Such frameworks can assist the integration of results from experimental radiobiology to risk evaluation and management practice. This research was funded by the Low Dose Radiation Research Program, BioI. and Environ. Research, US Dept. of Energy, Grant DE

  19. Bystander responses in low dose irradiated cells treated with plasma from gamma irradiated blood

    Energy Technology Data Exchange (ETDEWEB)

    Acheva, A; Georgieva, R; Rupova, I; Boteva, R [Laboratory Molecular Radiobiology and Epidemiology, National Centre of Radiobiology and Radiation Protection, 132 Kliment Ohridski blvd, Sofia 1756 (Bulgaria); Lyng, F [Radiation and Environmental Science Center, Dublin Institute of Technology, Kevin st, Dublin 8 (Ireland)], E-mail: anjin_a@mail.bg

    2008-02-01

    There are two specific low-dose radiation-induced responses that have been the focus of radiobiologists' interest in recent years. These are the bystander effect in non-irradiated cells and the adaptive response to a challenge dose after prior low dose irradiation. In the present study we have investigated if plasma from irradiated blood can act as a 'challenge dose' on low dose irradiated reporter epithelial cells (HaCaT cell line). The main aim was to evaluate the overall effect of low dose irradiation (0.05 Gy) of reporter cells and the influence of bystander factors in plasma from 0.5 Gy gamma irradiated blood on these cells. The effects were estimated by clonogenic survival of the reporter cells. We also investigated the involvement of reactive oxygen species (ROS) as potential factors involved in the bystander signaling. Calcium fluxes and mitochondrial membrane potential (MMP) depolarization were also examined as a marker for initiation of apoptosis in the reporter cells. The results show that there are large individual differences in the production of bystander effects and adaptive responses between different donors. These may be due to the specific composition of the donor plasma. The observed effects generally could be divided into two groups: adaptive responses and additive effects. ROS appeared to be involved in the responses of the low dose pretreated reporter cells. In all cases there was a significant decrease in MMP which may be an early event in the apoptotic process. Calcium signaling also appeared to be involved in triggering apoptosis in the low dose pretreated reporter cells. The heterogeneity of the bystander responses makes them difficult to be modulated for medical uses. Specific plasma characteristics that cause these large differences in the responses would need to be identified to make them useful for radiotherapy.

  20. Studies of Bystander Effects in 3-D Tissue Systems Using a Low-LET Microbeam

    Energy Technology Data Exchange (ETDEWEB)

    Brenner, David J.

    2009-07-17

    It is now accepted that biological effects may occur in cells that were not themselves traversed by ionizing radiation but are close to those that were. Little is known about the mechanism underlying such a bystander effect, although cell-to-cell communication is thought to be important. Previous work demonstrated a significant bystander effect for clonogenic survival and oncogenic transformation in C3H 10T(1/2) cells. Additional studies were undertaken to assess the importance of the degree of cell-to-cell contact at the time of irradiation on the magnitude of this bystander effect by varying the cell density. When 10% of cells were exposed to a range of 2-12 alpha particles, a significantly greater number of cells were inactivated when cells were irradiated at high density than at low density. In addition, the oncogenic transformation frequency was significantly higher in high-density cultures. These results suggest that when a cell is hit by radiation, the transmission of the bystander signal through cell-to-cell contact is an important mediator of the effect, implicating the involvement of intracellular communication through gap junctions. Additional studies to address the relationship between the bystander effect and the adaptive response were undertaken. A novel apparatus, where targeted and non-targeted cells were grown in close proximity, was used to investigate these. It was further examined whether a bystander effect or an adaptive response could be induced by a factor(s) present in the supernatants of cells exposed to a high or low dose of X-rays, respectively. When non-hit cells were co-cultured for 24 h with cells irradiated with 5 Gy alpha-particles, a significant increase in both cell killing and oncogenic transformation frequency was observed. If these cells were treated with 2 cGy X-rays 5 h before co-culture with irradiated cells, approximately 95% of the bystander effect was cancelled out. A 2.5-fold decrease in the oncogenic transformation

  1. Torpor shortens the period of Siberian hamster circadian rhythms.

    Science.gov (United States)

    Thomas, E M; Jewett, M E; Zucker, I

    1993-10-01

    We investigated the influence of ambient and body temperature (Ta and Tb) on circadian rhythms of gonadectomized male Siberian hamsters. Animals that entered torpor (Tb circadian periods (tau s) than did nontorpid hamsters at a Ta of 13 degrees C (24.17 +/- 0.05 vs. 24.33 +/- 0.04 h). The tau s of homeothermic hamsters were not affected by Ta change. Short-term decreases in Tb, rather than changes in Ta, appear to affect tau. Access to activity wheels inhibited expression of torpor in short daylengths and was associated with significant increases in body mass. Running wheel activity can mask or block specific short-day responses.

  2. Radiation and chemotherapy bystander effects induce early genomic instability events: telomere shortening and bridge formation coupled with mitochondrial dysfunction.

    LENUS (Irish Health Repository)

    Gorman, Sheeona

    2012-02-01

    The bridge breakage fusion cycle is a chromosomal instability mechanism responsible for genomic changes. Radiation bystander effects induce genomic instability; however, the mechanism driving this instability is unknown. We examined if radiation and chemotherapy bystander effects induce early genomic instability events such as telomere shortening and bridge formation using a human colon cancer explant model. We assessed telomere lengths, bridge formations, mitochondrial membrane potential and levels of reactive oxygen species in bystander cells exposed to medium from irradiated and chemotherapy-treated explant tissues. Bystander cells exposed to media from 2Gy, 5Gy, FOLFOX treated tumor and matching normal tissue showed a significant reduction in telomere lengths (all p values <0.018) and an increase in bridge formations (all p values <0.017) compared to bystander cells treated with media from unirradiated tissue (0Gy) at 24h. There was no significant difference between 2Gy and 5Gy treatments, or between effects elicited by tumor versus matched normal tissue. Bystander cells exposed to media from 2Gy irradiated tumor tissue showed significant depolarisation of the mitochondrial membrane potential (p=0.012) and an increase in reactive oxygen species levels. We also used bystander cells overexpressing a mitochondrial antioxidant manganese superoxide dismutase (MnSOD) to examine if this antioxidant could rescue the mitochondrial changes and subsequently influence nuclear instability events. In MnSOD cells, ROS levels were reduced (p=0.02) and mitochondrial membrane potential increased (p=0.04). These events were coupled with a decrease in percentage of cells with anaphase bridges and a decrease in the number of cells undergoing telomere length shortening (p values 0.01 and 0.028 respectively). We demonstrate that radiation and chemotherapy bystander responses induce early genomic instability coupled with defects in mitochondrial function. Restoring mitochondrial

  3. The Role of Bystander Effects in the Antitumor Activity of the Hypoxia-Activated Prodrug PR-104

    OpenAIRE

    Foehrenbacher, Annika; Patel, Kashyap; Abbattista, Maria R; Guise, Chris P.; Timothy W Secomb; Wilson, William R; Hicks, Kevin O.

    2013-01-01

    Activation of prodrugs in tumors (e.g., by bioreduction in hypoxic zones) has the potential to generate active metabolites that can diffuse within the tumor microenvironment. Such “bystander effects” may offset spatial heterogeneity in prodrug activation but the relative importance of this effect is not understood. Here, we quantify the contribution of bystander effects to antitumor activity for the first time, by developing a spatially resolved pharmacokinetic/pharmacodynamic (SR-PK/PD) mode...

  4. An examination of the bystander effect in multiple models: from cell line to in-vivo exposure

    OpenAIRE

    Vines, Alice, (Thesis)

    2007-01-01

    In recent years there has been a paradigm shift in radiobiology, to one which induces non-targeted effects, such as the bystander effect and genomic instability. The bystander effect has been defined as effects seen in cells that although never exposed to radiation, display similar effects to those that have, due to some form of communication with directly hit cells. This investigation aims to further the current understanding of this effect using three different models, cell lines, primary e...

  5. Critical role of gap junction communication, calcium and nitric oxide signaling in bystander responses to focal photodynamic injury

    OpenAIRE

    Calì, Bianca; Ceolin, Stefano; Ceriani, Federico; Bortolozzi, Mario; Agnellini, Andrielly H.R.; Zorzi, Veronica; Predonzani, Andrea; Bronte, Vincenzo; Molon, Barbara; Mammano, Fabio

    2015-01-01

    Ionizing and nonionizing radiation affect not only directly targeted cells but also surrounding “bystander” cells. The underlying mechanisms and therapeutic role of bystander responses remain incompletely defined. Here we show that photosentizer activation in a single cell triggers apoptosis in bystander cancer cells, which are electrically coupled by gap junction channels and support the propagation of a Ca2+ wave initiated in the irradiated cell. The latter also acts as source of nitric oxi...

  6. Regions of High Out-Of-Hospital Cardiac Arrest Incidence and Low Bystander CPR Rates in Victoria, Australia

    Science.gov (United States)

    Straney, Lahn D.; Bray, Janet E.; Beck, Ben; Finn, Judith; Bernard, Stephen; Dyson, Kylie; Lijovic, Marijana; Smith, Karen

    2015-01-01

    Background Out-of-hospital cardiac arrest (OHCA) remains a major public health issue and research has shown that large regional variation in outcomes exists. Of the interventions associated with survival, the provision of bystander CPR is one of the most important modifiable factors. The aim of this study is to identify census areas with high incidence of OHCA and low rates of bystander CPR in Victoria, Australia Methods We conducted an observational study using prospectively collected population-based OHCA data from the state of Victoria in Australia. Using ArcGIS (ArcMap 10.0), we linked the location of the arrest using the dispatch coordinates (longitude and latitude) to Victorian Local Government Areas (LGAs). We used Bayesian hierarchical models with random effects on each LGA to provide shrunken estimates of the rates of bystander CPR and the incidence rates. Results Over the study period there were 31,019 adult OHCA attended, of which 21,436 (69.1%) cases were of presumed cardiac etiology. Significant variation in the incidence of OHCA among LGAs was observed. There was a 3 fold difference in the incidence rate between the lowest and highest LGAs, ranging from 38.5 to 115.1 cases per 100,000 person-years. The overall rate of bystander CPR for bystander witnessed OHCAs was 62.4%, with the rate increasing from 56.4% in 2008–2010 to 68.6% in 2010–2013. There was a 25.1% absolute difference in bystander CPR rates between the highest and lowest LGAs. Conclusion Significant regional variation in OHCA incidence and bystander CPR rates exists throughout Victoria. Regions with high incidence and low bystander CPR participation can be identified and would make suitable targets for interventions to improve CPR participation rates. PMID:26447844

  7. Regions of High Out-Of-Hospital Cardiac Arrest Incidence and Low Bystander CPR Rates in Victoria, Australia.

    Directory of Open Access Journals (Sweden)

    Lahn D Straney

    Full Text Available Out-of-hospital cardiac arrest (OHCA remains a major public health issue and research has shown that large regional variation in outcomes exists. Of the interventions associated with survival, the provision of bystander CPR is one of the most important modifiable factors. The aim of this study is to identify census areas with high incidence of OHCA and low rates of bystander CPR in Victoria, Australia.We conducted an observational study using prospectively collected population-based OHCA data from the state of Victoria in Australia. Using ArcGIS (ArcMap 10.0, we linked the location of the arrest using the dispatch coordinates (longitude and latitude to Victorian Local Government Areas (LGAs. We used Bayesian hierarchical models with random effects on each LGA to provide shrunken estimates of the rates of bystander CPR and the incidence rates.Over the study period there were 31,019 adult OHCA attended, of which 21,436 (69.1% cases were of presumed cardiac etiology. Significant variation in the incidence of OHCA among LGAs was observed. There was a 3 fold difference in the incidence rate between the lowest and highest LGAs, ranging from 38.5 to 115.1 cases per 100,000 person-years. The overall rate of bystander CPR for bystander witnessed OHCAs was 62.4%, with the rate increasing from 56.4% in 2008-2010 to 68.6% in 2010-2013. There was a 25.1% absolute difference in bystander CPR rates between the highest and lowest LGAs.Significant regional variation in OHCA incidence and bystander CPR rates exists throughout Victoria. Regions with high incidence and low bystander CPR participation can be identified and would make suitable targets for interventions to improve CPR participation rates.

  8. Radiation-induced bystander effect in healthy G{sub 0} human lymphocytes: Biological and clinical significance

    Energy Technology Data Exchange (ETDEWEB)

    Belloni, Paola; Latini, Paolo [Department of Agrobiology and Agrochemistry, University of Tuscia, Via San Camillo De Lellis, I-01100 Viterbo (Italy); Palitti, Fabrizio, E-mail: palitti@unitus.it [Department of Agrobiology and Agrochemistry, University of Tuscia, Via San Camillo De Lellis, I-01100 Viterbo (Italy)

    2011-08-01

    To study the bystander effects, G{sub 0} human peripheral blood lymphocytes were X-irradiated with 0.1, 0.5 and 3 Gy. After 24 h, cell-free conditioned media from irradiated cultures were transferred to unexposed lymphocytes. Following 48 h of medium transfer, viability, induction of apoptosis, telomere shortening, reactive oxygen species (ROS) levels and micronuclei (after stimulation) were analyzed. A statistically significant decrement in cell viability, concomitant with the loss of mitochondrial membrane potential, telomere shortening, increases in hydrogen peroxide (H{sub 2}O{sub 2}) and superoxide anion (O{sub 2}{sup -}) with depletion of intracellular glutathione (GSH) level, and higher frequencies of micronuclei, were observed in bystander lymphocytes incubated with medium from 0.5 and 3 Gy irradiated samples, compared to lymphocytes unexposed. Furthermore, no statistically significant difference between the response to 0.5 and 3 Gy of irradiation in bystander lymphocytes, was found. However, when lymphocytes were irradiated with 0.1 Gy, no bystander effect with regard to viability, apoptosis, telomere length, and micronuclei was observed, although a high production of ROS level persisted. Radiation in the presence of the radical scavenger dimethyl sulfoxide (DMSO) suppressed oxidative stress induced by 3 Gy of X-rays with the effective elimination of bystander effects, suggesting a correlation between ROS and bystander signal formation in irradiated cells. The data propose that bystander effect might be mostly due to the reactions of radiation induced free radicals on DNA, with the existence of a threshold at which the bystander signal is not operative (0.1 Gy dose of X-rays). Our results may have clinical implications for health risk associated with radiation exposure.

  9. Radiation and chemotherapy bystander effects induce early genomic instability events: Telomere shortening and bridge formation coupled with mitochondrial dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Gorman, Sheeona; Tosetto, Miriam [Centre for Colorectal Disease, St. Vincent' s University Hospital, Elm Park, Dublin 4 (Ireland); Lyng, Fiona; Howe, Orla [Radiation and Environmental Science Centre, Dublin Institute of Technology and St. Luke' s Hospital, Dublin (Ireland); Sheahan, Kieran; O' Donoghue, Diarmuid; Hyland, John; Mulcahy, Hugh [Centre for Colorectal Disease, St. Vincent' s University Hospital, Elm Park, Dublin 4 (Ireland); O' Sullivan, Jacintha, E-mail: jacintha.osullivan@ucd.ie [Centre for Colorectal Disease, St. Vincent' s University Hospital, Elm Park, Dublin 4 (Ireland)

    2009-10-02

    The bridge breakage fusion cycle is a chromosomal instability mechanism responsible for genomic changes. Radiation bystander effects induce genomic instability; however, the mechanism driving this instability is unknown. We examined if radiation and chemotherapy bystander effects induce early genomic instability events such as telomere shortening and bridge formation using a human colon cancer explant model. We assessed telomere lengths, bridge formations, mitochondrial membrane potential and levels of reactive oxygen species in bystander cells exposed to medium from irradiated and chemotherapy-treated explant tissues. Bystander cells exposed to media from 2 Gy, 5 Gy, FOLFOX treated tumor and matching normal tissue showed a significant reduction in telomere lengths (all p values <0.018) and an increase in bridge formations (all p values <0.017) compared to bystander cells treated with media from unirradiated tissue (0 Gy) at 24 h. There was no significant difference between 2 Gy and 5 Gy treatments, or between effects elicited by tumor versus matched normal tissue. Bystander cells exposed to media from 2 Gy irradiated tumor tissue showed significant depolarisation of the mitochondrial membrane potential (p = 0.012) and an increase in reactive oxygen species levels. We also used bystander cells overexpressing a mitochondrial antioxidant manganese superoxide dismutase (MnSOD) to examine if this antioxidant could rescue the mitochondrial changes and subsequently influence nuclear instability events. In MnSOD cells, ROS levels were reduced (p = 0.02) and mitochondrial membrane potential increased (p = 0.04). These events were coupled with a decrease in percentage of cells with anaphase bridges and a decrease in the number of cells undergoing telomere length shortening (p values 0.01 and 0.028 respectively). We demonstrate that radiation and chemotherapy bystander responses induce early genomic instability coupled with defects in mitochondrial function. Restoring

  10. That's What Friends Are For: Bystander Responses to Friends or Strangers at Risk for Party Rape Victimization.

    Science.gov (United States)

    Katz, Jennifer; Pazienza, Rena; Olin, Rachel; Rich, Hillary

    2015-10-01

    The present research examined bystander responses to potential party rape scenarios involving either a friend or a stranger at risk. Undergraduate students (N = 151) imagined attending a party and seeing a man lead an intoxicated woman (friend or stranger) into a bedroom. After random assignment to conditions, participants reported on intentions to help, barriers to helping, victim blame, and empathic concern. As expected, based on their shared social group membership, bystanders intended to offer more help to friends than to strangers. Bystanders also reported more personal responsibility to help and more empathic concern when the potential victim was a friend rather than stranger. Observing a friend versus stranger at risk did not affect audience inhibition or perceived victim blame. Compared with women, men reported more blame and less empathic concern for potential victims. However, there were no gender differences in bystander intent to help or barriers to helping. In multivariate analyses, both responsibility to help and empathic concern for the potential victim uniquely predicted bystanders' intent to help a woman at risk for party rape. Results suggest that promoting social identification with peers at risk could increase bystander intervention. PMID:25349015

  11. Bystander Action in Situations of Dating and Sexual Aggression: A Mixed Methodological Study of High School Youth.

    Science.gov (United States)

    Edwards, Katie M; Rodenhizer-Stämpfli, Kara Anne; Eckstein, Robert P

    2015-12-01

    Bystander action is a critical component of dating and sexual aggression prevention; however, little is known about barriers and facilitators of bystander action among high school youth and in what situations youth are willing to engage in bystander action. The current study examined bystander action in situations of dating and sexual aggression using a mixed methodological design. Participants included primarily Caucasian (83.0%, n = 181) male (54.6%, n = 119) and female (44.5%, n = 97) high school youth (N = 218). Most (93.6%) students had the opportunity to take action during the past year in situations of dating or sexual aggression; being female and histories of dating and sexual aggression related to bystander action. Thematic analysis of the focus group data identified barriers (e.g., the aggression not meeting a certain threshold, anticipated negative consequences) to bystander action, as well as insight on promising forms of action (e.g., verbally telling the perpetrator to stop, getting a teacher); problematic intervention methods (e.g., threatening or using physical violence to stop the perpetrator) were also noted. Implications for programming are discussed.

  12. Protective effect of butylated hydroxytoluene (BHT) against the clastogenic acitivity of cadmium chloride and potassium dichromate in hamster ovary cells

    OpenAIRE

    Grillo Claudia A.; Seoane Analía I.; Dulout Fernando N.

    1999-01-01

    The effect of butylated hydroxytoluene (BHT), a widely used food additive, on chromosomal alterations induced by cadmium chloride (CC) and potassium dichromate (PD) in Chinese hamster ovary (CHO) cells was studied both at metaphase and anaphase-telophase. CHO cells were cultured for 15-16 h in the presence of PD (6.0, 9.0 or 12.0 mM), BHT (1.0 mg/ml), or PD plus BHT as well as CC (0.5, 1.0 and 2.0 mM), BHT or CC plus BHT for the analysis of chromosomal aberrations. To perform the anaphase-tel...

  13. Elk3 from hamster--a ternary complex factor with strong transcriptional repressor activity.

    Science.gov (United States)

    Hjortoe, Gertrud Malene; Weilguny, Dietmar; Willumsen, Berthe Marie

    2005-01-01

    Elk3 belongs to the Ets family of transcription factors, which are regulated by the Ras/mitogen-activated protein kinase-signaling pathway. In the absence of Ras, this protein is a strong inhibitor of transcription and may be directly involved in regulation of growth by downregulating the transcription of genes that are activated during entry into G1. We have isolated the Cricetulus griseus Elk3 gene from the Chinese hamster ovary (CHO) cell line and investigated the transcriptional potential of this factor. Transient transfections revealed that, in addition to its regulation of the c-fos promoter, Elk3 from CHO cells seems to inhibit other promoters controlling expression of proteins involved in G1/S phase progression; Cyclin D1 and DHFR. As has been described for the Elk3 homologs Net (Mouse) and Sap-2 (Human), the results of the present study further indicate that hamster Elk3 is a target of the Ras-Raf-MAPK pathway, and cotransfections with constitutively active H-ras relieves its negative transcriptional activity. No cells stably expressing exogenous Elk3 could be obtained, possibly due to an unspecified toxic or growth retarding effect. These findings support a possible role for Elk3 in growth regulation and reveal a high degree of homology for this protein across species. PMID:15684718

  14. Neuropeptide Y induces torpor-like hypothermia in Siberian hamsters.

    Science.gov (United States)

    Paul, Matthew J; Freeman, David A; Park, Jin Ho; Dark, John

    2005-09-01

    Intracerebroventricular (ICV) injections of neuropeptide Y (NPY) are known to decrease body temperature (Tb) of laboratory rats by 1-3 degrees C. Several NPY pathways in the brain terminate in hypothalamic structures involved in energy balance and thermoregulation. Laboratory rats are homeothermic, maintaining Tb within a narrow range. We examined the effect of ICV injected NPY on Tb in the heterothermic Siberian hamster (Phodopus sungorus), a species that naturally undergoes daily torpor in which Tb decreases by as much as 15-20 degrees C. Minimum effective dose was determined in preliminary testing then various doses of NPY were tested in cold-acclimated Siberian hamsters while food was withheld. NPY markedly reduced Tb in the heterothermic Siberian hamster. In addition, the reduction in Tb in 63% of the observations was sufficient to reach the criterion for daily torpor (Tb Siberian hamster. NPY treatment may be activating hypothalamic systems that normally integrate endogenous torpor-producing signals and initiate torpor.

  15. Asymmetric learning to avoid heterospecific males in Mesocricetus hamsters

    OpenAIRE

    delBarco-Trillo, Javier; Johnston, Robert E.

    2012-01-01

    If a female mates with a male of a closely related species, her fitness is likely to decline. Consequently, females may develop behavioral mechanisms to avoid mating with heterospecific males. In some species, one such mechanism is for adult females to learn to discriminate against heterospecific males after exposure to such males. We have previously shown that adult, female Syrian hamsters (Mesocricetus auratus) learn to discriminate against male Turkish hamsters (Mesocricetus brandti) after...

  16. Experimental Models in Syrian Golden Hamster Replicate Human Acute Pancreatitis

    OpenAIRE

    Yunan Wang; Abudurexiti Kayoumu; Guotao Lu; Pengfei Xu; Xu Qiu; Liye Chen; Rong Qi; Shouxiong Huang; Weiqin Li; Yuhui Wang; George Liu

    2016-01-01

    The hamster has been shown to share a variety of metabolic similarities with humans. To replicate human acute pancreatitis with hamsters, we comparatively studied the efficacy of common methods, such as the peritoneal injections of caerulein, L-arginine, the retrograde infusion of sodium taurocholate, and another novel model with concomitant administration of ethanol and fatty acid. The severity of pancreatitis was evaluated by serum amylase activity, pathological scores, myeloperoxidase acti...

  17. Fasting-induced daily torpor in desert hamsters (Phodopus roborovskii).

    Science.gov (United States)

    Chi, Qing-Sheng; Wan, Xin-Rong; Geiser, Fritz; Wang, De-Hua

    2016-09-01

    Daily torpor is frequently expressed in small rodents when facing energetically unfavorable ambient conditions. Desert hamsters (Phodopus roborovskii, ~20g) appear to be an exception as they have been described as homeothermic. However, we hypothesized that they can use torpor because we observed reversible decreases of body temperature (Tb) in fasted hamsters. To test this hypothesis we (i) randomly exposed fasted summer-acclimated hamsters to ambient temperatures (Tas) ranging from 5 to 30°C or (ii) supplied them with different rations of food at Ta 23°C. All desert hamsters showed heterothermy with the lowest mean Tb of 31.4±1.9°C (minimum, 29.0°C) and 31.8±2.0°C (minimum, 29.0°C) when fasted at Ta of 23°C and 19°C, respectively. Below Ta 19°C, the lowest Tb and metabolic rate increased and the proportion of hamsters using heterothermy declined. At Ta 5°C, nearly all hamsters remained normothermic by increasing heat production, suggesting that the heterothermy only occurs in moderately cold conditions, perhaps to avoid freezing at extremely low Tas. During heterothermy, Tbs below 31°C with metabolic rates below 25% of those during normothermia were detected in four individuals at Ta of 19°C and 23°C. Consequently, by definition, our observations confirm that fasted desert hamsters are capable of shallow daily torpor. The negative correlation between the lowest Tbs and amount of food supply shows that heterothermy was mainly triggered by food shortage. Our data indicate that summer-acclimated desert hamsters can express fasting-induced shallow daily torpor, which may be of significance for energy conservation and survival in the wild. PMID:27215346

  18. Chimpanzees' Bystander Reactions to Infanticide: An Evolutionary Precursor of Social Norms?

    Science.gov (United States)

    von Rohr, Claudia Rudolf; van Schaik, Carel P; Kissling, Alexandra; Burkart, Judith M

    2015-06-01

    Social norms-generalized expectations about how others should behave in a given context-implicitly guide human social life. However, their existence becomes explicit when they are violated because norm violations provoke negative reactions, even from personally uninvolved bystanders. To explore the evolutionary origin of human social norms, we presented chimpanzees with videos depicting a putative norm violation: unfamiliar conspecifics engaging in infanticidal attacks on an infant chimpanzee. The chimpanzees looked far longer at infanticide scenes than at control videos showing nut cracking, hunting a colobus monkey, or displays and aggression among adult males. Furthermore, several alternative explanations for this looking pattern could be ruled out. However, infanticide scenes did not generally elicit higher arousal. We propose that chimpanzees as uninvolved bystanders may detect norm violations but may restrict emotional reactions to such situations to in-group contexts. We discuss the implications for the evolution of human morality.

  19. Chimpanzees' Bystander Reactions to Infanticide: An Evolutionary Precursor of Social Norms?

    Science.gov (United States)

    von Rohr, Claudia Rudolf; van Schaik, Carel P; Kissling, Alexandra; Burkart, Judith M

    2015-06-01

    Social norms-generalized expectations about how others should behave in a given context-implicitly guide human social life. However, their existence becomes explicit when they are violated because norm violations provoke negative reactions, even from personally uninvolved bystanders. To explore the evolutionary origin of human social norms, we presented chimpanzees with videos depicting a putative norm violation: unfamiliar conspecifics engaging in infanticidal attacks on an infant chimpanzee. The chimpanzees looked far longer at infanticide scenes than at control videos showing nut cracking, hunting a colobus monkey, or displays and aggression among adult males. Furthermore, several alternative explanations for this looking pattern could be ruled out. However, infanticide scenes did not generally elicit higher arousal. We propose that chimpanzees as uninvolved bystanders may detect norm violations but may restrict emotional reactions to such situations to in-group contexts. We discuss the implications for the evolution of human morality. PMID:26108616

  20. The effect of victims' responses to overt bullying on same-sex peer bystander reactions.

    Science.gov (United States)

    Sokol, Nicole; Bussey, Kay; Rapee, Ronald M

    2015-10-01

    This study investigated the impact of victims' responses to overt bullying on peer bystanders' attitudes and reactions. Fifth- and seventh-grade students (N = 206; M(age) = 11.13 and 13.18 years, respectively) completed online questionnaires about gender-consistent videotaped hypothetical bullying scenarios in which the victims' responses (angry, sad, confident, ignoring) were experimentally manipulated. Victims' responses significantly influenced bystanders' attitudes towards the victim, perceptions of the victimization, emotional reactions, and behavioral intentions. In general, angry victims elicited more negative reactions, sad victims elicited greater intentions to act, while incidents involving confident victims were perceived as less serious. Several variations depending on the bullying type and students' grade, gender, and personal experiences with bullying were evident. Implications for individual-level and peer-level anti-bullying interventions are discussed. PMID:26407835

  1. Understanding the Role of Bystanders and Peer Support in School Bullying

    Directory of Open Access Journals (Sweden)

    Helen Cowie

    2014-04-01

    Full Text Available Research into school bullying has traditionally focussed on the actual protagonists – the perpetrators and the targets. Consequently, we know a great deal about the psychological characteristics of bullies and victims and the consequences of bullying in undermining the emotional well-being of both targets and perpetrators. While an understanding of the personal aspects of the bully-victim relationship is important, it only addresses part of the issue. Bullying is experienced within a group of peers who adopt different participant roles and who experience a range of emotions. In this article, I argue that bullies do not act alone but rely on reinforcement from their immediate group of friends as well as the tacit approval of the onlookers. This article explores the conflicting emotions often experienced by the bystanders. It also makes some suggestions about interventions to empower bystanders to take action against bullying through, for example, such interventions as peer support.

  2. Diffusion of Cardiopulmonary Resuscitation Training to Chinese Immigrants with Limited English Proficiency

    OpenAIRE

    Mei Po Yip; Brandon Ong; Shin Ping Tu; Devora Chavez; Brooke Ike; Ian Painter; Ida Lam; Bradley, Steven M.; Coronado, Gloria D.; Meischke, Hendrika W.

    2011-01-01

    Cardiopulmonary resuscitation (CPR) is an effective intervention for prehospital cardiac arrest. Despite all available training opportunities for CPR, disparities exist in participation in CPR training, CPR knowledge, and receipt of bystander CPR for certain ethnic groups. We conducted five focus groups with Chinese immigrants who self-reported limited English proficiency (LEP). A bilingual facilitator conducted all the sessions. All discussions were taped, recorded, translated, and trans...

  3. Modulation of modeled microgravity on radiation-induced bystander effects in Arabidopsis thaliana

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Ting [Key Laboratory of Ion Beam Bio-engineering, Hefei Institutes of Physical Science, Chinese Academy of Sciences and Anhui Province, Hefei, Anhui 230031 (China); Sun, Qiao [Space Molecular Biological Lab, China Academy of Space Technology, Beijing 100086 (China); Xu, Wei; Li, Fanghua [Key Laboratory of Ion Beam Bio-engineering, Hefei Institutes of Physical Science, Chinese Academy of Sciences and Anhui Province, Hefei, Anhui 230031 (China); Li, Huasheng; Lu, Jinying [Space Molecular Biological Lab, China Academy of Space Technology, Beijing 100086 (China); Wu, Lijun; Wu, Yuejin [Key Laboratory of Ion Beam Bio-engineering, Hefei Institutes of Physical Science, Chinese Academy of Sciences and Anhui Province, Hefei, Anhui 230031 (China); Liu, Min [Space Molecular Biological Lab, China Academy of Space Technology, Beijing 100086 (China); Bian, Po [Key Laboratory of Ion Beam Bio-engineering, Hefei Institutes of Physical Science, Chinese Academy of Sciences and Anhui Province, Hefei, Anhui 230031 (China)

    2015-03-15

    Highlights: • The effects of microgravity on the radiation-induced bystander effects (RIBE) were definitely demonstrated. • The effects of microgravity on RIBE might be divergent for different biological events. • The microgravity mainly modified the generation or transport of bystander signals at early stage. - Abstract: Both space radiation and microgravity have been demonstrated to have inevitable impact on living organisms during space flights and should be considered as important factors for estimating the potential health risk for astronauts. Therefore, the question whether radiation effects could be modulated by microgravity is an important aspect in such risk evaluation. Space particles at low dose and fluence rate, directly affect only a fraction of cells in the whole organism, which implement radiation-induced bystander effects (RIBE) in cellular response to space radiation exposure. The fact that all of the RIBE experiments are carried out in a normal gravity condition bring forward the need for evidence regarding the effect of microgravity on RIBE. In the present study, a two-dimensional rotation clinostat was adopted to demonstrate RIBE in microgravity conditions, in which the RIBE was assayed using an experimental system of root-localized irradiation of Arabidopsis thaliana (A. thaliana) plants. The results showed that the modeled microgravity inhibited significantly the RIBE-mediated up-regulation of expression of the AtRAD54 and AtRAD51 genes, generation of reactive oxygen species (ROS) and transcriptional activation of multicopy P35S:GUS, but made no difference to the induction of homologous recombination by RIBE, showing divergent responses of RIBE to the microgravity conditions. The time course of interaction between the modeled microgravity and RIBE was further investigated, and the results showed that the microgravity mainly modulated the processes of the generation or translocation of the bystander signal(s) in roots.

  4. Radiation-induced bystander effects: Are they good bad or both?

    International Nuclear Information System (INIS)

    The different contributions are as follow: the current events on the cellular responses to irradiation ( part one and two); From physico-chemistry to radiobiology: new knowledge (part one and two); Radiation-induced bystander effects: are they good bad or both; recognition of the multi visceral failure in the acute irradiation syndrome; integrated approach of the tissue carcinogenesis: differential effect sane tissue-tumoral tissue; differential diagnosis of thyroid cancers by the transcriptoma analysis. (N.C.)

  5. Simulating Social Situations in Immersive Virtual Reality - A Study of Bystander Responses to Violent Emergencies

    OpenAIRE

    Rovira Perez, A.

    2016-01-01

    The goal of this research is to show how immersive virtual reality (IVR) can be used to study human responses to extreme emergencies in social situations. Participants interact realistically with animated virtual humans. We show this through experimental studies of bystander responses to a violent confrontation, and find that there are conditions under which people intervene to help virtual characters that are threatened. We go on to show that a reinforcement learning (RL) method can capture ...

  6. Eosinophils: Offenders or General Bystanders in Allergic Airway Disease and Pulmonary Immunity?

    OpenAIRE

    Akuthota, Praveen; Xenakis, Jason J.; Weller, Peter F.

    2011-01-01

    Eosinophils have long been noted to be present in asthma and other forms of pulmonary inflammation, but whether they act as true offenders or merely as bystanders has been a point of uncertainty. However, in recent years, there has been increasing evidence suggesting that eosinophils are not passive cells in the respiratory system, acting only as markers of allergic inflammation. This review discusses key evidence from animal models and human clinical trials that support the importance of eos...

  7. Video calls from lay bystanders to dispatch centers - risk assessment of information security

    OpenAIRE

    Hasvold Per; Bolle Stein R; Henriksen Eva

    2011-01-01

    Abstract Background Video calls from mobile phones can improve communication during medical emergencies. Lay bystanders can be instructed and supervised by health professionals at Emergency Medical Communication Centers. Before implementation of video mobile calls in emergencies, issues of information security should be addressed. Methods Information security was assessed for risk, based on the information security standard ISO/IEC 27005:2008. A multi-professional team used structured brainst...

  8. Electronic Cigarettes and Indoor Air Quality: A Simple Approach to Modeling Potential Bystander Exposures to Nicotine

    OpenAIRE

    Stéphane Colard; Grant O'Connell; Thomas Verron; Xavier Cahours; Pritchard, John D.

    2014-01-01

    There has been rapid growth in the use of electronic cigarettes (“vaping”) in Europe, North America and elsewhere. With such increased prevalence, there is currently a debate on whether the aerosol exhaled following the use of e-cigarettes has implications for the quality of air breathed by bystanders. Conducting chemical analysis of the indoor environment can be costly and resource intensive, limiting the number of studies which can be conducted. However, this can be modelled reasonably acc...

  9. Dexamethasone inhibits the HSV-tk/ ganciclovir bystander effect in malignant glioma cells

    International Nuclear Information System (INIS)

    HSV-tk/ ganciclovir (GCV) gene therapy has been extensively studied in the setting of brain tumors and largely relies on the bystander effect. Large studies have however failed to demonstrate any significant benefit of this strategy in the treatment of human brain tumors. Since dexamethasone is a frequently used symptomatic treatment for malignant gliomas, its interaction with the bystander effect and the overall efficacy of HSV-TK gene therapy ought to be assessed. Stable clones of TK-expressing U87, C6 and LN18 cells were generated and their bystander effect on wild type cells was assessed. The effects of dexamethasone on cell proliferation and sensitivity to ganciclovir were assessed with a thymidine incorporation assay and a MTT test. Gap junction mediated intercellular communication was assessed with microinjections and FACS analysis of calcein transfer. The effect of dexamethasone treatment on the sensitivity of TK-expressing to FAS-dependent apoptosis in the presence or absence of ganciclovir was assessed with an MTT test. Western blot was used to evidence the effect of dexamethasone on the expression of Cx43, CD95, CIAP2 and BclXL. Dexamethasone significantly reduced the bystander effect in TK-expressing C6, LN18 and U87 cells. This inhibition results from a reduction of the gap junction mediated intercellular communication of these cells (GJIC), from an inhibition of their growth and thymidine incorporation and from a modulation of the apoptotic cascade. The overall efficacy of HSV-TK gene therapy is adversely affected by dexamethasone co-treatment in vitro. Future HSV-tk/ GCV gene therapy clinical protocols for gliomas should address this interference of corticosteroid treatment

  10. Outcomes of a Bystander Intervention Community Health Service-Learning Project.

    Science.gov (United States)

    Decker, Kim; Hensel, Desiree; Fasone, Leslie

    2016-01-01

    The purpose of this article is to describe the integration of a college bystander intervention service-learning project into an entry-level community clinical course in a prelicensure program and its outcomes. Two years of data from 118 students showed that students helped improve campus safety while growing as professionals and gaining leadership and health promotion skills. Approximately one-third of the students described a specific incident in which they intervened in an ambiguous situation. PMID:26633150

  11. Investigation of the bystander effect in MRC5 cells after acute and fractionated irradiation in vitro

    Directory of Open Access Journals (Sweden)

    Shokouhozaman Soleymanifard

    2014-01-01

    Full Text Available Radiation-induced bystander effect (RIBE has been defined as radiation responses observed in nonirradiated cells. It has been the focus of investigators worldwide due to the deleterious effects it induces in nonirradiated cells. The present study was performed to investigate whether acute or fractionated irradiation will evoke a differential bystander response in MRC5 cells. A normal human cell line (MRC5, and a human lung tumor cell line (QU-DB were exposed to 0, 1, 2, and 4Gy of single acute or fractionated irradiation of equal fractions with a gap of 6 h. The MRC5 cells were supplemented with the media of irradiated cells and their micronucleus frequency was determined. The micronucleus frequency after single and fractionated irradiation did not vary significantly in the MRC5 cells conditioned with autologous or QU-DB cell-irradiated media, except for 4Gy where the frequency of micronucleated cells was lower in those MRC5 cells cultured in the media of QU-DB-exposed with a single dose of 4Gy. Our study demonstrates that the radiation-induced bystander effect was almost similar after single acute and fractionated exposure in MRC5 cells.

  12. What is the role of the bystander response in radionuclide therapies?

    Directory of Open Access Journals (Sweden)

    Darren eBrady

    2013-08-01

    Full Text Available Radionuclide therapy for cancer is undergoing a renaissance, with a wide range of radionuclide and clinical delivery systems currently under investigation. Dosimetry at the cellular and subcellular level is complex with inhomogeneity and incomplete targeting of all cells such that some tumour cells will receive little or no direct radiation energy. There is now sufficient preclinical evidence of a bystander response which can modulate the biology of these unirradiated cells with current research demonstrating both protective and inhibitory responses. Dependence upon fraction of irradiated cells has also been found has and the presence of functional gap junctions appears to be import for several bystander responses. The selection of either high or low LET radionuclides may be critical. While low LET radionuclides appear to have a bystander response proportional to dose, the dose-response from high LET radionuclides are more complex. In media transfer experiments a U shaped response curve has been demonstrated for high LET treatments. However this U shaped response has not been seen with co-culture experiments and its relevance remains uncertain. For high LET treatments there is a suggestion that dose rate effects may also be important with inhibitory effects noted with 125I labelling study and a stimulatory seen with 123I labelling in one study.

  13. Bystander effects induced by medium from carbon-ion irradiated human cancer cells

    Institute of Scientific and Technical Information of China (English)

    WANG Ju-Fang; LI Wen-Jian; ZHOU Guang-Ming; DANG Bing-Rong; MA Qiu-Feng; FENG Yan

    2005-01-01

    The bystander effects induced by medium from human hepatoma SMMC-7721 and adenocarcinoma F56 cells irradiated with carbon ions were investigated. It was found that the survival fraction (SF) of the irradiated cells decreased exponentially along with the increased dose. SMMC-7721 cells were more radiosensitive than F56 cells.The plating efficiency (PE) of the non-irradiated cells treated with irradiated conditioned medium (ICM) was obviously lower than the PE of control cells for SMMC-7721 cells but not for F56 cells. Moreover, the reduced PE and SF by ICM treatment were more significant for 1Gy irradiation than for 6Gy irradiation on SMMC-7721 cells. These results suggest that the irradiated cells can secrete factor(s) into medium that is cytotoxic to bystander non-irradiated cells. The bystander effects are dependent on cell genotype presented at the time of irradiation and radiation dose.This makes impact on the precise estimation of the effects of radiation and tumor radiotherapy.

  14. Addressing sexual and relationship violence in the LGBT community using a bystander framework.

    Science.gov (United States)

    Potter, Sharyn J; Fountain, Kim; Stapleton, Jane G

    2012-01-01

    Sexual and relationship violence are two major public health issues that affect an alarming number of undergraduate students. As a result, many colleges and universities have protocols to serve victims of these forms of violence. Despite federal legislation stating that all students should have equitable experiences, current protocols and programs focus primarily on heterosexual students. College student victims of sexual and relationship violence who identify as lesbian, gay, bisexual, or transgender can face particular challenges, including disclosure of their sexual and gender orientations, and revictimization when seeking services. In recent years an increasing number of campuses have adopted bystander prevention strategies to address sexual and relationship violence. These strategies seek to engage community members in the prevention of sexual and relationship violence by training them to identify and safely intervene in situations where sexual or relationship violence is about to occur, is occurring, or has occurred. In this article we review published bystander prevention strategies that focus on preventing sexual and relationship violence in the campus community, and discuss how bystander strategies are addressing or can address relationship and sexual violence in the LGBT community.

  15. Theoretical models and simulation codes to investigate bystander effects and cellular communication at low doses

    Science.gov (United States)

    Ballarini, F.; Alloni, D.; Facoetti, A.; Mairani, A.; Nano, R.; Ottolenghi, A.

    Astronauts in space are continuously exposed to low doses of ionizing radiation from Galactic Cosmic Rays During the last ten years the effects of low radiation doses have been widely re-discussed following a large number of observations on the so-called non targeted effects in particular bystander effects The latter consist of induction of cytogenetic damage in cells not directly traversed by radiation most likely as a response to molecular messengers released by directly irradiated cells Bystander effects which are observed both for lethal endpoints e g clonogenic inactivation and apoptosis and for non-lethal ones e g mutations and neoplastic transformation tend to show non-linear dose responses This might have significant consequences in terms of low-dose risk which is generally calculated on the basis of the Linear No Threshold hypothesis Although the mechanisms underlying bystander effects are still largely unknown it is now clear that two types of cellular communication i e via gap junctions and or release of molecular messengers into the extracellular environment play a fundamental role Theoretical models and simulation codes can be of help in elucidating such mechanisms In the present paper we will review different available modelling approaches including one that is being developed at the University of Pavia The focus will be on the different assumptions adopted by the various authors and on the implications of such assumptions in terms of non-targeted radiobiological damage and more generally low-dose

  16. Differential effects of p53 on bystander phenotypes induced by gamma ray and high LET heavy ion radiation

    Science.gov (United States)

    He, Mingyuan; Dong, Chen; Konishi, Teruaki; Tu, Wenzhi; Liu, Weili; Shiomi, Naoko; Kobayashi, Alisa; Uchihori, Yukio; Furusawa, Yoshiya; Hei, Tom K.; Dang, Bingrong; Shao, Chunlin

    2014-04-01

    High LET particle irradiation has several potential advantages over γ-rays such as p53-independent response. The purpose of this work is to disclose the effect of p53 on the bystander effect induced by different LET irradiations and underlying mechanism. Lymphocyte cells of TK6 (wild type p53) and HMy2.CIR (mutated p53) were exposed to either low or high LET irradiation, then their mitochondrial dysfunction and ROS generation were detected. The micronuclei (MN) induction in HL-7702 hepatocytes co-cultured with irradiated lymphocytes was also measured. It was found that the mitochondrial dysfunction, p66Shc activation, and intracellular ROS were enhanced in TK6 but not in HMy2.CIR cells after γ-ray irradiation, but all of them were increased in both cell lines after carbon and iron irradiation. Consistently, the bystander effect of MN formation in HL-7702 cells was only triggered by γ-irradiated TK6 cells but not by γ-irradiated HMy2.CIR cells. But this bystander effect was induced by both lymphocyte cell lines after heavy ion irradiation. PFT-μ, an inhibitor of p53, only partly inhibited ROS generation and bystander effect induced by 30 keV/μm carbon-irradiated TK6 cells but failed to suppress the bystander effect induced by the TK6 cells irradiated with either 70 keV/μm carbon or 180 keV/μm iron. The mitochondrial inhibitors of rotenone and oligomycin eliminated heavy ion induced ROS generation in TK6 and HMy2.CIR cells and hence diminished the bystander effect on HL-7702 cells. These results clearly demonstrate that the bystander effect is p53-dependent for low LET irradiation, but it is p53-independent for high LET irradiation which may be because of p53-independent ROS generation due to mitochondrial dysfunction.

  17. Expression of FHIT in AHH-1 cells irradiated by 60Co γ-ray and bystander effect cells

    International Nuclear Information System (INIS)

    Objective: To investigate the expression of FHIT gene in the 60Co gamma-ray irradiated human lymphocytoblast (AHH-1) cell and the bystander effect cell, and to explore the function of FHIT gene in the bystander effect of ionizing radiation. Method: Preparation of bystander effect cell model: after inadiated with different dose of 60Co gamma-ray (0, 2, 5 Gy), the directly irradiated AHH-1 cells were collected immediately by centrifugation and co-cultivated with non-irradiated cells in Transwell, forming the bystander effect group P1. In addition, some culture media supematant of directly irradiated cells were transferred to the non- irradiated cells culture medium, forming the group P2. Then cells were collected at 0, 6, 12, and 24 h after irradiation and the total RNA and protein were extracted. RT-PCR and Western blot were performed to determine the FHIT mRNA and protein level, respectively. Flow cytometry assay and cell counting were conducted to detect the alteration of cell cycle and cell proliferation, respectively at 0, 24 h after irradiation. Results: The mRNA level of FHIT gene among control cells, directly irradiated cells and bystander cells showed no obvious difference, while the FHIT protein level of the directly irradiated cells and bystander cells was significantly down-regulated compared with the control cells (F=102.45, P2 phase arrest and obviously inhibited the proliferation ability. Conclusions: 2 and 5 Gy of 60Co γ-ray irradiated AHH-1 cells can result in down regulation of the FHIT protein expression, which suggests that FHIT gene is involved in the process of bystander effect induced by irradiation. (authors)

  18. Social thermoregulation and torpor in the Siberian hamster.

    Science.gov (United States)

    Jefimow, Małgorzata; Głabska, Marta; Wojciechowski, Michał S

    2011-04-01

    Social thermoregulation and huddling bring about energy benefits to animals sharing a nest because of the smaller surface-to-volume ratio of a huddle and the higher local temperature in the nest. We tested whether living in groups and huddling affect daily torpor, metabolic rate and seasonal changes in the body mass of a small heterothermic rodent, the Siberian hamster (Phodopus sungorus), housed under semi-natural conditions both singly and in groups of four litter-mates. We predicted that in hamsters housed in groups: (1) synchronized torpor bouts would be longer and deeper than non-synchronized ones but shallower than in solitary hamsters, (2) seasonal variations in metabolic rate would be lower than in solitary hamsters, and (3) the winter decrease in body mass would be smaller in grouped than in singly housed hamsters. We found that group housing led to a smaller decrease in body mass in winter, and affected the length and depth of daily torpor. In group-living hamsters more than 50% of all torpor episodes were synchronized and torpid animals were often found in huddles formed of all cage-mates. The longest and deepest torpor bouts in groups were recorded when all animals in a group entered torpor simultaneously. Although the minimum body temperature during torpor was higher, torpor duration was slightly longer than in solitary hamsters. We did not record significant differences in the body mass-adjusted rate of oxygen consumption between solitary and grouped animals, either in the cold or at the lower critical temperature. We conclude that social thermoregulation enables maintenance of a larger body mass, and thus a larger body fat content, which can ensure better body condition at the beginning of the reproductive season.

  19. The Significance of the Bystander Effect: Modeling, Experiments, and More Modeling

    Energy Technology Data Exchange (ETDEWEB)

    Brenner, David J.

    2009-07-22

    Non-targeted (bystander) effects of ionizing radiation are caused by intercellular signaling; they include production of DNA damage and alterations in cell fate (i.e. apoptosis, differentiation, senescence or proliferation). Biophysical models capable of quantifying these effects may improve cancer risk estimation at radiation doses below the epidemiological detection threshold. Understanding the spatial patterns of bystander responses is important, because it provides estimates of how many bystander cells are affected per irradiated cell. In a first approach to modeling of bystander spatial effects in a three-dimensional artificial tissue, we assumed the following: (1) The bystander phenomenon results from signaling molecules (S) that rapidly propagate from irradiated cells and decrease in concentration (exponentially in the case of planar symmetry) as distance increases. (2) These signals can convert cells to a long-lived epigenetically activated state, e.g. a state of oxidative stress; cells in this state are more prone to DNA damage and behavior alterations than normal and therefore exhibit an increased response (R) for many end points (e.g. apoptosis, differentiation, micronucleation). These assumptions were implemented by a mathematical formalism and computational algorithms. The model adequately described data on bystander responses in the 3D system using a small number of adjustable parameters. Mathematical models of radiation carcinogenesis are important for understanding mechanisms and for interpreting or extrapolating risk. There are two classes of such models: (1) long-term formalisms that track pre-malignant cell numbers throughout an entire lifetime but treat initial radiation dose-response simplistically and (2) short-term formalisms that provide a detailed initial dose-response even for complicated radiation protocols, but address its modulation during the subsequent cancer latency period only indirectly. We argue that integrating short- and long

  20. Adaptation of the interspersed repetitive sequence polymerase chain reaction to the isolation of mouse DNA probes from somatic cell hybrids on a hamster background

    International Nuclear Information System (INIS)

    A strategy for the rapid isolation of DNA probes from radiation-fusion Chinese hamster cell hybrids containing overlapping portions of the murine X chromosome based on the interspersed repetitive sequence polymerase chain reaction (IRS-PCR) previously used with human somatic cell hybrids has been developed. This specific amplification of mouse DNA on a hamster background depends on the use of primers directed to the B2 short interspersed repeat element family and the R repeat, from the long interspersed repeat element family, L1. Two sets of amplification conditions, which gave specific amplification of mouse DNA from either a mouse X-monochromosomal hybrid or irradiation-fusion hybrids having reduced X content, were defined. The mouse X-only chromosome hybrid yielded approximately 20 discrete reproducible bands, while the irradiation-fusion hybrids yielded between 1 and 10 discrete products. Comparison of different irradiation-fusion hybrids has allowed the definition of both specific and shared products corresponding to different regions within the overlapping X-chromosome fragments present within these hybrids. Use of such hybrids and the IRS-PCR technique has allowed the isolation of probes corresponding to the central region of the mouse X chromosome that contains the X-inactivation center. The method should be widely applicable to the isolation of mouse DNA sequences from mouse hybrid cell lines on either human or Chinese hamster backgrounds

  1. Bystander Position Taking in School Bullying: The Role of Positive Identity, Self-Efficacy, and Self-Determination

    Directory of Open Access Journals (Sweden)

    Sandra K. M. Tsang

    2011-01-01

    Full Text Available School bullying has become an explicit, burgeoning problem challenging the healthy development of children and adolescents in Hong Kong. Many bullying prevention and intervention programs focus on victims and bullies, with bystanders treated as either nonexistent or irrelevant. This paper asserts that bystanders actually play pivotal roles in deciding whether the bullying process and dynamics are benign or adversarial. Bystanders' own abilities and characteristics often influence how they respond to victims and bullies. “P.A.T.H.S. to Adulthood: A Jockey Club Youth Enhancement Scheme” (P.A.T.H.S. = Positive Adolescent Training through Holistic Social Programmes is an evidence-based positive youth development program which shows that primary intervention programs have constructive impacts on junior secondary school students' beliefs and behavior. This paper asserts that intrapsychic qualities, namely identity, self-efficacy, and self-determination, greatly influence how bystanders react in school bullying situations. The paper also explains how classroom-based educational programs based on the P.A.T.H.S. model have been designed to help junior secondary school students strengthen these characteristics, so that they can be constructive bystanders when they encounter school bullying.

  2. Dependence of the bystander effect for micronucleus formation on dose of heavy-ion radiation in normal human fibroblasts

    International Nuclear Information System (INIS)

    Ionising radiation-induced bystander effects are well recognised, but its dependence on dose or linear energy transfer (LET) is still a matter of debate. To test this, 49 sites in confluent cultures of AG01522D normal human fibroblasts were targeted with microbeams of carbon (103 keV μm-1), neon (375 keV μm-1) and argon ions (1260 keV μm-1) and evaluated for the bystander-induced formation of micronucleus that is a kind of a chromosome aberration. Targeted exposure to neon and argon ions significantly increased the micronucleus frequency in bystander cells to the similar extent irrespective of the particle numbers per site of 1- 6. In contrast, the bystander micronucleus frequency increased with increasing the number of carbon-ion particles in a range between 1 and 3 particles per site and was similar in a range between 3 and 8 particles per site. These results suggest that the bystander effect of heavy ions for micronucleus formation depends on dose. (authors)

  3. Social context modulates food hoarding in Syrian hamsters

    Directory of Open Access Journals (Sweden)

    Bibiana Montoya

    2016-09-01

    Full Text Available The effect of the presence of a con-specific in the temporal organization of food hoarding was studied in two varieties of Syrian hamster (Mesocricetus auratus: golden and long-haired. Four male hamsters of each variety were used. Their foraging behavior was observed during four individual and four shared trials in which animals were not competing for the same food source or territory. During individual trials, long-haired hamsters consumed food items directly from the food source, transporting and hoarding only remaining pieces. During shared trials, the long-haired variety hoarded food items before consumption, and increased the duration of hoarding trips, food handling in the storage, and cache size. Golden hamsters maintained the same temporal organization of hoarding behavior (i.e., hoarding food items before consumption throughout both individual and shared trials. However, the golden variety increased handling time at the food source and decreased the duration of hoarding trips, the latency of hoarding and storing size throughout the shared trials. In Syrian hamsters, the presence of a con-specific may signal high probability of food source depletion suggesting that social pressures over food availability might facilitate hoarding behavior. Further studies are required to evaluate cost-benefit balance of food hoarding and the role of cache pilferage in this species.

  4. Role of caloric homeostasis and reward in alcohol intake in Syrian golden hamsters

    OpenAIRE

    Gulick, Danielle; Green, Alan I.

    2010-01-01

    The Syrian golden hamster drinks alcohol readily, but only achieves moderate blood alcohol levels, and does not go through withdrawal from alcohol. Because the hamster is a model of caloric homeostasis, both caloric content and reward value may contribute to the hamster’s alcohol consumption. The current study examines alcohol consumption in the hamster when a caloric or non-caloric sweet solution is concurrently available and caloric intake in the hamster before, during, and after exposure t...

  5. Impact of Dispatcher‐Assisted Bystander Cardiopulmonary Resuscitation on Neurological Outcomes in Children With Out‐of‐Hospital Cardiac Arrests: A Prospective, Nationwide, Population‐Based Cohort Study

    OpenAIRE

    Goto, Yoshikazu; Maeda, Tetsuo; GOTO, YUMIKO

    2014-01-01

    Background The impact of dispatcher‐assisted bystander cardiopulmonary resuscitation (CPR) on neurological outcomes in children is unclear. We investigated whether dispatcher‐assisted bystander CPR shows favorable neurological outcomes (Cerebral Performance Category scale 1 or 2) in children with out‐of‐hospital cardiac arrest (OHCA). Methods and Results Children (n=5009, age

  6. 9 CFR 3.36 - Primary enclosures used to transport live guinea pigs and hamsters.

    Science.gov (United States)

    2010-01-01

    ... live guinea pigs and hamsters. 3.36 Section 3.36 Animals and Animal Products ANIMAL AND PLANT HEALTH..., Care, Treatment, and Transportation of Guinea Pigs and Hamsters Transportation Standards § 3.36 Primary enclosures used to transport live guinea pigs and hamsters. No person subject to the Animal...

  7. Genitourinary changes in hamsters infected and reinfected with Trypanosoma cruzi

    Directory of Open Access Journals (Sweden)

    Cabrine-Santos Marlene

    2003-01-01

    Full Text Available Authors describe genitourinary changes in male hamsters infected and reinfected with Trypanosoma cruzi. Changes in genital organs have been described in human and in experimental chagasic infection. Genital dysfunctions in chronic chagasic patients affect ejaculation, libido and sexual potency, and testis biopsies may show arrested maturation of germ cells, oligozoospermia and azoospermia. Sixty-five male hamsters were inoculated and reinoculated with 2x10³ trypomastigotes of T. cruzi VIC strain, and 22 non-infected animals constituted the control group. Animals were necropsied and fragments from testis, epididymis, seminal vesicle and bladder were collected and stained with hematoxylin-eosin. Peroxidase anti-peroxidase procedure was utilized to detect tissue parasitism. T. cruzi nests were found in testis, epididymis and seminal vesicle of these hamsters. Such parasitism plays a role in the origin of genital lesions observed in humans and laboratory animals during chronic chagasic infection.

  8. Homeostatic regulation of sleep in arrhythmic Siberian hamsters.

    Science.gov (United States)

    Larkin, Jennie E; Yokogawa, Tohei; Heller, H Craig; Franken, Paul; Ruby, Norman F

    2004-07-01

    Sleep is regulated by independent yet interacting circadian and homeostatic processes. The present study used a novel approach to study sleep homeostasis in the absence of circadian influences by exposing Siberian hamsters to a simple phase delay of the photocycle to make them arrhythmic. Because these hamsters lacked any circadian organization, their sleep homeostasis could be studied in the absence of circadian interactions. Control animals retained circadian rhythmicity after the phase shift and re-entrained to the phase-shifted photocycle. These animals displayed robust daily sleep-wake rhythms with consolidated sleep during the light phase beginning about 1 h after light onset. This marked sleep-wake pattern was circadian in that it persisted in constant darkness. The distribution of sleep in the arrhythmic hamsters over 24 h was similar to that in the light phase of rhythmic animals. Therefore, daily sleep amounts were higher in arrhythmic animals compared with rhythmic ones. During 2- and 6-h sleep deprivations (SD), it was more difficult to keep arrhythmic hamsters awake than it was for rhythmic hamsters. Because the arrhythmic animals obtained more non-rapid eye movement sleep (NREMS) during the SD, they showed a diminished compensatory response in NREMS EEG slow-wave activity during recovery sleep. When amounts of sleep during the SD were taken into account, there were no differences in sleep homeostasis between experimental and control hamsters. Thus loss of circadian control did not alter the homeostatic response to SD. This supports the view that circadian and homeostatic influences on sleep regulation are independent processes.

  9. Autonomic nervous dysfunction in hamsters infected with West Nile virus.

    Directory of Open Access Journals (Sweden)

    Hong Wang

    Full Text Available Clinical studies and case reports clearly document that West Nile virus (WNV can cause respiratory and gastrointestinal (GI complications. Other functions controlled by the autonomic nervous system may also be directly affected by WNV, such as bladder and cardiac functions. To investigate how WNV can cause autonomic dysfunctions, we focused on the cardiac and GI dysfunctions of rodents infected with WNV. Infected hamsters had distension of the stomach and intestines at day 9 after viral challenge. GI motility was detected by a dye retention assay; phenol red dye was retained more in the stomachs of infected hamsters as compared to sham-infected hamsters. The amplitudes of electromygraphs (EMGs of intestinal muscles were significantly reduced. Myenteric neurons that innervate the intestines, in addition to neurons in the brain stem, were identified to be infected with WNV. These data suggest that infected neurons controlling autonomic function were the cause of GI dysfunction in WNV-infected hamsters. Using radiotelemetry to record electrocardiograms and to measure heart rate variability (HRV, a well-accepted readout for autonomic function, we determined that HRV and autonomic function were suppressed in WNV-infected hamsters. Cardiac histopathology was observed at day 9 only in the right atrium, which was coincident with WNV staining. A subset of WNV infected cells was identified among cells with hyperpolarization-activated cyclic nucleotide-gated potassium channel 4 (HCN4 as a marker for cells in the sinoatrial (SA and atrioventricular (AV nodes. The unique contribution of this study is the discovery that WNV infection of hamsters can lead to autonomic dysfunction as determined by reduced HRV and reduced EMG amplitudes of the GI tract. These data may model autonomic dysfunction of the human West Nile neurological disease.

  10. Asbestos cement dust inhalation by hamsters

    Energy Technology Data Exchange (ETDEWEB)

    Wehner, A.P.; Dagle, G.E.; Cannon, W.C.; Buschbom, R.L. (Pacific Northwest Laboratories, Richland, WA (USA))

    1978-12-01

    Two groups of 96 male Syrian golden hamsters were exposed to respirable asbestos cement aerosol at concentrations of approximately 1 and approximately 10 micrograms/liter, respectively, 3 hours/day, 5 days/week. Average fiber counts ranged from 5 to about 120 fibers/cm3. Each group was randomly divided into six subgroups of 16 animals. The first subgroup was sacrificed after 3 months of exposure, the second after 6 months, and the third after 15 months. The fourth subgroup was withdrawn from exposure after 3 months, observed for an additional 3 months, and then sacrificed. The fifth and sixth subgroups were withdrawn after 3 and 6 months of exposure, respectively, and maintained for observation up to the 15-month exposure point of the third subgroup at which time all surviving animals were sacrificed. All other experimental procedures were similar to those delineated in a previous publication describing the development of an animal model, techniques, and an exposure system for asbestos cement dust inhalation. The asbestos cement exposures had no significant effect on body weight and mortality of the animals. Higher aerosol concentration and longer exposure times increased the number of macrophages and ferruginous bodies found in the lungs of the exposed animals. Recovery periods had no effect on the incidence of macrophages and ferruginous bodies. The incidence of very slight to slight fibrosis in the animals sacrificed after 15 months of exposure shows a significant (P less than 0.01) trend when the untreated control group and the 1 and 10 microgram/liter dose level groups are compared, indicating a dose-response relationship. Development of minimal fibrosis continued in animals withdrawn from exposure. No primary carcinomas of the lung and respiratory tract and no mesotheliomas were found.

  11. Bystander responses to a violent incident in an immersive virtual environment.

    Science.gov (United States)

    Slater, Mel; Rovira, Aitor; Southern, Richard; Swapp, David; Zhang, Jian J; Campbell, Claire; Levine, Mark

    2013-01-01

    Under what conditions will a bystander intervene to try to stop a violent attack by one person on another? It is generally believed that the greater the size of the crowd of bystanders, the less the chance that any of them will intervene. A complementary model is that social identity is critical as an explanatory variable. For example, when the bystander shares common social identity with the victim the probability of intervention is enhanced, other things being equal. However, it is generally not possible to study such hypotheses experimentally for practical and ethical reasons. Here we show that an experiment that depicts a violent incident at life-size in immersive virtual reality lends support to the social identity explanation. 40 male supporters of Arsenal Football Club in England were recruited for a two-factor between-groups experiment: the victim was either an Arsenal supporter or not (in-group/out-group), and looked towards the participant for help or not during the confrontation. The response variables were the numbers of verbal and physical interventions by the participant during the violent argument. The number of physical interventions had a significantly greater mean in the in-group condition compared to the out-group. The more that participants perceived that the Victim was looking to them for help the greater the number of interventions in the in-group but not in the out-group. These results are supported by standard statistical analysis of variance, with more detailed findings obtained by a symbolic regression procedure based on genetic programming. Verbal interventions made during their experience, and analysis of post-experiment interview data suggest that in-group members were more prone to confrontational intervention compared to the out-group who were more prone to make statements to try to diffuse the situation.

  12. Bystander responses to a violent incident in an immersive virtual environment.

    Directory of Open Access Journals (Sweden)

    Mel Slater

    Full Text Available Under what conditions will a bystander intervene to try to stop a violent attack by one person on another? It is generally believed that the greater the size of the crowd of bystanders, the less the chance that any of them will intervene. A complementary model is that social identity is critical as an explanatory variable. For example, when the bystander shares common social identity with the victim the probability of intervention is enhanced, other things being equal. However, it is generally not possible to study such hypotheses experimentally for practical and ethical reasons. Here we show that an experiment that depicts a violent incident at life-size in immersive virtual reality lends support to the social identity explanation. 40 male supporters of Arsenal Football Club in England were recruited for a two-factor between-groups experiment: the victim was either an Arsenal supporter or not (in-group/out-group, and looked towards the participant for help or not during the confrontation. The response variables were the numbers of verbal and physical interventions by the participant during the violent argument. The number of physical interventions had a significantly greater mean in the in-group condition compared to the out-group. The more that participants perceived that the Victim was looking to them for help the greater the number of interventions in the in-group but not in the out-group. These results are supported by standard statistical analysis of variance, with more detailed findings obtained by a symbolic regression procedure based on genetic programming. Verbal interventions made during their experience, and analysis of post-experiment interview data suggest that in-group members were more prone to confrontational intervention compared to the out-group who were more prone to make statements to try to diffuse the situation.

  13. Use of CB hamsters in the study of Treponema pertenue.

    Science.gov (United States)

    Schell, R F; Le Frock, J L; Babu, J P; Chan, J K

    1979-10-01

    The CB/Ss LAK strain of inbred hamster was used as a model for studies of infection with Treponema pertenue and of acquired resistance to it. When infected, this strain developed cutaneous lesions which lasted for six to seven months, even in the presence of peak titres of antitreponemal antibody. The rate of appearance and resolution of these lesions varied with the size of the inoculum. The infected hamsters' inguinal lymph nodes increased significantly in weight and teemed with treponemes for several weeks. Animals infected for eight or 10 weeks obtained quick resolution of their lesions by treatment with penicillin and were thereafter resistant to reinfection. PMID:509189

  14. Apoptosis is signalled early by low doses of ionising radiation in a radiation-induced bystander effect

    Energy Technology Data Exchange (ETDEWEB)

    Furlong, Hayley, E-mail: hayley.furlong@dit.ie [DIT Centre for Radiation and Environmental Science, Focas Research Institute, Dublin Institute of Technology, Kevin St, Dublin 8 (Ireland); School of Biological Sciences, College of Sciences and Health, Dublin Institute of Technology, Kevin St, Dublin 8 (Ireland); Mothersill, Carmel [Medical Physics and Applied Radiation Sciences, Nuclear Research Building, 1280 Hamilton, Ontario L8S 4K1 (Canada); Lyng, Fiona M. [DIT Centre for Radiation and Environmental Science, Focas Research Institute, Dublin Institute of Technology, Kevin St, Dublin 8 (Ireland); Howe, Orla [DIT Centre for Radiation and Environmental Science, Focas Research Institute, Dublin Institute of Technology, Kevin St, Dublin 8 (Ireland); School of Biological Sciences, College of Sciences and Health, Dublin Institute of Technology, Kevin St, Dublin 8 (Ireland)

    2013-01-15

    Highlights: ► Molecular mechanisms involved in the production of a radiation induced bystander effect are not well known. ► We investigate gene expression changes in apoptotic genes in both direct and bystander responses. ► We demonstrate initiation of the apoptotic cascade in a bystander response. ► Lower doses reveal a specific but differential response related to apoptosis compared to higher doses. - Abstract: It is known that ionising radiation (IR) induces a complex signalling apoptotic cascade post-exposure to low doses ultimately to remove damaged cells from a population, specifically via the intrinsic pathway. Therefore, it was hypothesised that bystander reporter cells may initiate a similar apoptotic response if exposed to low doses of IR (0.05 Gy and 0.5 Gy) and compared to directly irradiated cells. Key apoptotic genes were selected according to their role in the apoptotic cascade; tumour suppressor gene TP53, pro-apoptotic Bax and anti-apoptotic Bcl2, pro-apoptotic JNK and anti-apoptotic ERK, initiator caspase 2 and 9 and effector caspase 3, 6 and 7. The data generated consolidated the role of apoptosis following direct IR exposure for all doses and time points as pro-apoptotic genes such as Bax and JNK as well as initiator caspase 7 and effector caspase 3 and 9 were up-regulated. However, the gene expression profile for the bystander response was quite different and more complex in comparison to the direct response. The 0.05 Gy dose point had a more significant apoptosis gene expression profile compared to the 0.5 Gy dose point and genes were not always expressed within 1 h but were sometimes expressed 24 h later. The bystander data clearly demonstrates initiation of the apoptotic cascade by the up-regulation of TP53, Bax, Bcl-2, initiator caspase 2 and effector caspase 6. The effector caspases 3 and 7 of the bystander samples demonstrated down-regulation in their gene expression levels at 0.05 Gy and 0.5 Gy at both time points therefore not

  15. Debriefing bystanders of out-of-hospital cardiac arrest is valuable

    DEFF Research Database (Denmark)

    Møller, Thea Palsgaard; Hansen, Carolina Malta; Fjordholt, Martin;

    2014-01-01

    , positively influencing the ability to cope with the emotional reactions and the cognitive perception of own performance and motivates improvement of CPR skills. Importantly, it increases confidence to provide CPR in the future. Implementation of telephone debriefing to bystanders at Emergency Medical...... the phenomenological approach. RESULTS: Six themes emerged from analysis of debriefing audio files: (1) identification of OHCA; (2) emotional and perceptual experience with OHCA; (3) collaboration with healthcare professionals; (4) patients outcome; (5) coping with the experience and (6) general reflections. When...

  16. HL60 human premyelocitic cell line as a model system for bystander response

    International Nuclear Information System (INIS)

    Complete text of publication follows. Objective: to evaluate HL60 human premyelocitic cell line as a model system to study bystander response. Methods: HL60 cell line, isolated from the blood of a patient affected by premyelocitic leukemia, has 45-46 chromosomes with abnormalities mainly on chromosomes 5, 8 and X and can undergo chemical-induced in vitro differentiation. Differentiation gives rise to granulocytes, monocytes or macrophages depending on the drug used. We define as proliferative (AP) cells those in log phase of growth with less than 10 passages from thawing and as differentiated (D) cells those treated with 10 nM TPA (phorbol ester) for 72 hours. Phorbol ester treatment induces differentiation to monocytes and macrophages. Differentiation has been evaluated through the expression of differentiation cluster membrane antigens (CD95, CD9 and CD14). Results: AP cells resulted positive for CD95 and negative for CD9 and CD14, while D cells resulted positive for CD9 and negative for CD95 and CD14. Our data on AP and D cells showed that: (i) the level of intracellular reactive oxygen and nitrogen species (ROS and RNS) is lower in D cells compared to AP cells; (ii) radiation induced DNA damage (single and double strand breaks, SSB and DSB, as measured with the comet assay technique) is lower in D cells than in AP cells. This different radiosensitivity can be related to the higher degree of compactness of nuclear structure in D cells. Radiation induced bystander effect (BE) was analyzed with the medium transfer technique. The medium from irradiated, with 0.5 Gy of γ-rays, AP cells was collected after 0, 2, 4 and 24 hours from irradiation and added to non irradiated log phase cells. The frequency of micronuclei formation in bystander cells was measured by using the cytokinesis block technique by adding cytochalasin B to the non irradiated culture together with the irradiated medium. Preliminary data indicate about 1.4-fold increase in micronuclei formation in

  17. Bringing in the target audience in bystander social marketing materials for communities: suggestions for practitioners.

    Science.gov (United States)

    Potter, Sharyn J; Stapleton, Jane G

    2011-06-01

    The Know Your Power™ social marketing campaign images model active bystander behaviors that target audience members can use in situations where sexual and relationship violence and stalking are occurring, have occurred, or have the potential to occur. In this practitioner note, we describe strategies that we have used to engage target audience members in the development of the social marketing campaign that we hope can be used by practitioners. We give examples from the development and evaluation of the Know Your Power(TM) social marketing campaign that used focus group and other types of feedback from the target audience to inform the direction of the campaign.

  18. Preventing sexual aggression among college men: an evaluation of a social norms and bystander intervention program.

    Science.gov (United States)

    Gidycz, Christine A; Orchowski, Lindsay M; Berkowitz, Alan D

    2011-06-01

    Men and women living in randomly selected 1st-year dormitories participated in tailored single-sex sexual assault prevention or risk-reduction programs, respectively. An evaluation of the men's project is presented (N = 635). The program incorporated social norms and bystander intervention education and had an impact on self-reported sexual aggression and an effect on men's perceptions that their peers would intervene when they encountered inappropriate behavior in others. Relative to the control group, participants also reported less reinforcement for engaging in sexually aggressive behavior, reported fewer associations with sexually aggressive peers, and indicated less exposure to sexually explicit media. PMID:21571742

  19. Inhibitory effects of Zengshengping fractions on DMBA-induced buccal pouch carcinogenesis in hamsters

    Institute of Scientific and Technical Information of China (English)

    GUAN Xiao-bing; SUN Zheng; CHEN Xiao-xin; WU Hong-ru; ZHANG Xin-yan

    2012-01-01

    Background Zengshengping (ZSP) tablets had inhibitory effects on oral precancerous lesions by reducing the incidence of oral cancer.However,the severe liver toxicity caused by systemic administration of ZSP limits the long-term use of this anti-cancer drug.The purpose of this study was to evaluate the tumor inhibitory effects due to the topical application of extracts from ZSP,a Chinese herbal drug,on 7,12-dimethlbenz(a)anthracene (DMBA) induced oral tumors in hamsters.The study also investigated the anti-cancer mechanisms of the ZSP extracts on oral carcinogenesis.Methods DMBA (0.5%) was applied topically to the buccal pouches of Syrian golden hamsters (6-8 weeks old) three times per week for six weeks in order to induce the development of oral tumors.Different fractions of ZSP were either applied topically to the oral tumor lesions or fed orally at varying dosages to animals with oral tumors for 18 weeks.Tumor volume was measured by histopathological examination.Tumor cell proliferation was evaluated by counting BrdU labeled cells and by Western blotting for mitogen-activated protein kinase (MAPK) protein levels.The protein levels of apoptosis marker Caspase-3 and regulator Bcl-2 protein were also measured by Western blotting.Results Topical application of DMBA to the left pouch of hamsters induced oral tumor formation.Animals treated with DMBA showed a loss in body weight while animals treated with ZSP maintained normal body weights.Both the ZSP n-butanol fraction and water fraction significantly reduced tumor volume by 32.6% (P <0.01) and 22.9% (P <0.01)respectively.Topical application of ZSP also markedly decreased the BrdU-positive cell numbers in oral tumor lesions and reduced the expression level of MAPK.In addition,ZSP promoted tumor cell apoptosis by increasing Caspase-3 expression but decreasing Bcl-2 protein production.Conclusion The n-butanol and water fractions of ZSP are effective at inhibiting tumor cell proliferation and stimulating

  20. Melatonin production accompanies arousal from daily torpor in Siberian hamsters.

    Science.gov (United States)

    Larkin, Jennie E; Yellon, Steven M; Zucker, Irving

    2003-01-01

    Arousal from deep hibernation is accompanied by a transient rise of melatonin (Mel) in circulation; there are no comparable analyses of Mel concentrations in species that undergo much shallower, shorter duration episodes of daily torpor. Serum Mel concentrations were determined during arousal from both natural daily torpor and torpor induced by 2-deoxy-D-glucose (2-DG) treatment (2,500 mg/kg, intraperitoneal [IP]); blood samples were drawn from the retro-orbital sinus of anesthetized Siberian hamsters. For animals kept in darkness during torpor, Mel concentrations were highest during early arousal when thermogenesis is maximal, and they decreased as body temperature increased during arousal and returned to baseline once euthermia was reestablished. In hamsters kept in the light during the torpor bout, Mel concentrations were elevated above basal values during arousal, but the response was significantly blunted in comparison with values recorded in darkness. Increased Mel concentrations were detected in hamsters only during arousal from torpor (either natural or 2-DG induced) and were not simply a result of the drug treatment; hamsters that remained euthermic or manifested mild hypothermia after drug treatment maintained basal Mel concentrations. We propose that increased Mel production may reflect enhanced sympathetic activation associated with intense thermogenesis during arousal from torpor rather than an adjustment of the circadian rhythm of Mel secretion.

  1. Bioavailability and disposition of solanine in rats and hamsters

    NARCIS (Netherlands)

    Groen K; Pereboom-de Fauw DPKH; Besamusca P; Beekhof PK; Speijers GJA; Derks HJGM

    1992-01-01

    The toxicokinetics of [3H]-alpha-solanine after oral (po) and intravenous (iv) administration in rats and hamsters were studied, in order to decide which is the most appropriate model in risk assessment studies. The iv dose was 54 mug/kg; the oral dose was 170 mug/kg. After iv administration, the

  2. Development of Taenia pisiformis in golden hamster (Mesocricetus auratus

    Directory of Open Access Journals (Sweden)

    Maravilla Pablo

    2011-07-01

    Full Text Available Abstract The life cycle of Taenia pisiformis includes canines as definitive hosts and rabbits as intermediate hosts. Golden hamster (Mesocricetus auratus is a rodent that has been successfully used as experimental model of Taenia solium taeniosis. In the present study we describe the course of T. pisiformis infection in experimentally infected golden hamsters. Ten females, treated with methyl-prednisolone acetate were infected with three T. pisiformis cysticerci each one excised from one rabbit. Proglottids released in faeces and adults recovered during necropsy showed that all animals were infected. Eggs obtained from the hamsters' tapeworms, were assessed for viability using trypan blue or propidium iodide stains. Afterwards, some rabbits were inoculated with eggs, necropsy was performed after seven weeks and viable cysticerci were obtained. Our results demonstrate that the experimental model of adult Taenia pisiformis in golden hamster can replace the use of canines in order to study this parasite and to provide eggs and adult tapeworms to be used in different types of experiments.

  3. DOSE RESPONSE OF ELASTASE-INDUCED EMPHYSEMA IN HAMSTERS

    Science.gov (United States)

    Elastase-induced emhysema in hamsters was studied using pulmonary function tests in an effort to develop techniques for determining the effects of air pollutants on the progression of this disease. It appears that as little as 6 units of elastase produces mild emphysema in hamste...

  4. Extracellular signaling through the microenvironment: a hypothesis relating carcinogenesis, bystander effects, and genomic instability

    Science.gov (United States)

    Barcellos-Hoff, M. H.; Brooks, A. L.; Chatterjee, A. (Principal Investigator)

    2001-01-01

    Cell growth, differentiation and death are directed in large part by extracellular signaling through the interactions of cells with other cells and with the extracellular matrix; these interactions are in turn modulated by cytokines and growth factors, i.e. the microenvironment. Here we discuss the idea that extracellular signaling integrates multicellular damage responses that are important deterrents to the development of cancer through mechanisms that eliminate abnormal cells and inhibit neoplastic behavior. As an example, we discuss the action of transforming growth factor beta (TGFB1) as an extracellular sensor of damage. We propose that radiation-induced bystander effects and genomic instability are, respectively, positive and negative manifestations of this homeostatic process. Bystander effects exhibited predominantly after a low-dose or a nonhomogeneous radiation exposure are extracellular signaling pathways that modulate cellular repair and death programs. Persistent disruption of extracellular signaling after exposure to relatively high doses of ionizing radiation may lead to the accumulation of aberrant cells that are genomically unstable. Understanding radiation effects in terms of coordinated multicellular responses that affect decisions regarding the fate of a cell may necessitate re-evaluation of radiation dose and risk concepts and provide avenues for intervention.

  5. Ombud’s Corner: Bystanders, you can have a role too

    CERN Multimedia

    Sudeshna Datta-Cockerill

    2015-01-01

    If you find yourself repeatedly witnessing a situation of inter personal conflict or tension between other colleagues, you have a choice: you can either turn a blind eye to it or you can try to help. In the latter case, you may wish to get another perspective or some guidance before taking steps.   Stefan, Paul and Lucas work together on a challenging project. Over time, Lucas has started to notice Paul’s verbally aggressive behaviour towards Stefan: he frequently criticises him in public, cuts him short at meetings when he is trying to make his point and is known to make derogatory remarks about him behind his back. Stefan does not seem to react but the tension between them is evident and Lucas feels increasingly uncomfortable in their company. It is never easy to know whether or not to intervene in these delicate situations, and the ‘bystander effect’ - where people do nothing - tends to prevail in most workplace cultures. Bystanders hesitate to act because th...

  6. The role of gender, values, and culture in adolescent bystanders' strategies.

    Science.gov (United States)

    Tamm, Anni; Tulviste, Tiia

    2015-02-01

    We examined the relationship between adolescent bystanders' strategies for intervening in the bullying-like situation and their gender, values, and cultural origin. The sample consisted of 682 Estonian and Russian-Estonian adolescents (M age = 13.02 years). They were shown a video of a bullying-like situation with a non-intervening adult bystander and asked to describe what they would do if they, instead of the adult, witnessed that situation. Only 10% said that they would not intervene. Girls were more likely than boys to suggest multiple actions. Adolescents who valued conformity were less likely to propose using physical aggression. Doing nothing was less likely suggested by those who placed more importance on conformity and less on power. Estonian adolescents were more likely than their Russian-Estonian peers to suggest finding out what is going on, and less likely to say that they would do nothing. The findings suggest that although most adolescents express willingness to help the victim, they might not actually know how to intervene.

  7. The role of gender, values, and culture in adolescent bystanders' strategies.

    Science.gov (United States)

    Tamm, Anni; Tulviste, Tiia

    2015-02-01

    We examined the relationship between adolescent bystanders' strategies for intervening in the bullying-like situation and their gender, values, and cultural origin. The sample consisted of 682 Estonian and Russian-Estonian adolescents (M age = 13.02 years). They were shown a video of a bullying-like situation with a non-intervening adult bystander and asked to describe what they would do if they, instead of the adult, witnessed that situation. Only 10% said that they would not intervene. Girls were more likely than boys to suggest multiple actions. Adolescents who valued conformity were less likely to propose using physical aggression. Doing nothing was less likely suggested by those who placed more importance on conformity and less on power. Estonian adolescents were more likely than their Russian-Estonian peers to suggest finding out what is going on, and less likely to say that they would do nothing. The findings suggest that although most adolescents express willingness to help the victim, they might not actually know how to intervene. PMID:24919991

  8. Electronic Cigarettes and Indoor Air Quality: A Simple Approach to Modeling Potential Bystander Exposures to Nicotine

    Directory of Open Access Journals (Sweden)

    Stéphane Colard

    2014-12-01

    Full Text Available There has been rapid growth in the use of electronic cigarettes (“vaping” in Europe, North America and elsewhere. With such increased prevalence, there is currently a debate on whether the aerosol exhaled following the use of e-cigarettes has implications for the quality of air breathed by bystanders. Conducting chemical analysis of the indoor environment can be costly and resource intensive, limiting the number of studies which can be conducted. However, this can be modelled reasonably accurately based on empirical emissions data and using some basic assumptions. Here, we present a simplified model, based on physical principles, which considers aerosol propagation, dilution and extraction to determine the potential contribution of a single puff from an e-cigarette to indoor air. From this, it was then possible to simulate the cumulative effect of vaping over time. The model was applied to a virtual, but plausible, scenario considering an e-cigarette user and a non-user working in the same office space. The model was also used to reproduce published experimental studies and showed good agreement with the published values of indoor air nicotine concentration. With some additional refinements, such an approach may be a cost-effective and rapid way of assessing the potential exposure of bystanders to exhaled e-cigarette aerosol constituents.

  9. Seasonal aspects of sleep in the Djungarian hamster

    Directory of Open Access Journals (Sweden)

    Deboer Tom

    2003-05-01

    Full Text Available Abstract Background Changes in photoperiod and ambient temperature trigger seasonal adaptations in the physiology and behaviour of many species, including the Djungarian hamster. Exposure of the hamsters to a short photoperiod and low ambient temperature leads to a reduction of the polyphasic distribution of sleep and waking over the light and dark period. In contrast, a long photoperiod enhances the daily sleep-wake amplitude leading to a decline of slow-wave activity in NREM sleep within the light period. It is unknown whether these changes can be attributed specifically to photoperiod and/or ambient temperature, or whether endogenous components are contributing factors. The influence of endogenous factors was investigated by recording sleep in Djungarian hamsters invariably maintained at a low ambient temperature and fully adapted to a short photoperiod. The second recording was performed when they had returned to summer physiology, despite the maintenance of the 'winter' conditions. Results Clear winter-summer differences were seen in sleep distribution, while total sleep time was unchanged. A significantly higher light-dark cycle modulation in NREM sleep, REM sleep and waking was observed in hamsters in the summer physiological state compared to those in the winter state. Moreover, only in summer, REM sleep episodes were longer and waking bouts were shorter during the light period compared to the dark period. EEG power in the slow-wave range (0.75–4.0 Hz in both NREM sleep and REM sleep was higher in animals in the summer physiological state than in those in the 'winter' state. In winter SWA in NREM sleep was evenly distributed over the 24 h, while in summer it decreased during the light period and increased during the dark period. Conclusion Endogenous changes in the organism underlie the differences in sleep-wake redistribution we have observed previously in hamsters recorded in a short and long photoperiod.

  10. Cell damage from radiation-induced bystander effects for different cell densities simulated by a mathematical model via cellular automata

    Energy Technology Data Exchange (ETDEWEB)

    Meireles, Sincler P. de; Santos, Adriano M.; Grynberg, Suely Epsztein, E-mail: spm@cdtn.b, E-mail: amsantos@cdtn.b, E-mail: seg@cdtn.b [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil); Nunes, Maria Eugenia S., E-mail: mariaeugenia@iceb.ufop.b [Universidade Federal de Ouro Preto (UFOP), MG (Brazil)

    2011-07-01

    During recent years, there has been a shift from an approach focused entirely on DNA as the main target of ionizing radiation to a vision that considers complex signaling pathways in cells and among cells within tissues. Several newly recognized responses were classified as the so-called non-target responses in which the biological effects are not directly related to the amount of energy deposited in the DNA of cells that were traversed by radiation. In 1992 the bystander effect was described referring to a series of responses such as death, chromosomal instability or other abnormalities that occur in non-irradiated cells that came into contact with irradiated cells or medium from irradiated cells. In this work, we have developed a mathematical model via cellular automata, to quantify cell death induced by the bystander effect. The model is based on experiments with irradiated cells conditioned medium which suggests that irradiated cells secrete molecules in the medium that are capable of damaging other cells. The computational model consists of two-dimensional cellular automata which is able to simulate the transmission of bystander signals via extrinsic route and via Gap junctions. The model has been validated by experimental results in the literature. The time evolution of the effect and the dose-response curves were obtained in good accordance to them. Simulations were conducted for different values of bystander and irradiated cell densities with constant dose. From this work, we have obtained a relationship between cell density and effect. (author)

  11. Perceptions of pesticides exposure risks by operators, workers, residents and bystanders in Greece, Italy and the UK

    NARCIS (Netherlands)

    Remoundou, K.; Brennan, M.; Sacchettini, G.; Panzone, L.; Butler-Ellis, M.C.; Capri, E.; Charistou, A.; Chaideftou, E.; Gerritsen-Ebben, M.G.; Machera, K.; Spanoghe, P.; Glass, R.; Marchis, A.; Doanngoc, K.; Hart, A.; Frewer, L.J.

    2015-01-01

    The EU Directive on the sustainable use of pesticides (EU128/2009/EC) requires European Member States to develop training activities targeting occupational exposure to pesticides, and communication material aimed at residents and bystanders. Risk perceptions, knowledge and attitudes associated with

  12. Cell damage from radiation-induced bystander effects for different cell densities simulated by a mathematical model via cellular automata

    International Nuclear Information System (INIS)

    During recent years, there has been a shift from an approach focused entirely on DNA as the main target of ionizing radiation to a vision that considers complex signaling pathways in cells and among cells within tissues. Several newly recognized responses were classified as the so-called non-target responses in which the biological effects are not directly related to the amount of energy deposited in the DNA of cells that were traversed by radiation. In 1992 the bystander effect was described referring to a series of responses such as death, chromosomal instability or other abnormalities that occur in non-irradiated cells that came into contact with irradiated cells or medium from irradiated cells. In this work, we have developed a mathematical model via cellular automata, to quantify cell death induced by the bystander effect. The model is based on experiments with irradiated cells conditioned medium which suggests that irradiated cells secrete molecules in the medium that are capable of damaging other cells. The computational model consists of two-dimensional cellular automata which is able to simulate the transmission of bystander signals via extrinsic route and via Gap junctions. The model has been validated by experimental results in the literature. The time evolution of the effect and the dose-response curves were obtained in good accordance to them. Simulations were conducted for different values of bystander and irradiated cell densities with constant dose. From this work, we have obtained a relationship between cell density and effect. (author)

  13. Bystanders' Reactions to Bullying: A Cross-Cultural Analysis of Personal Correlates among Italian and Singaporean Students

    Science.gov (United States)

    Pozzoli, Tiziana; Ang, Rebecca P.; Gini, Gianluca

    2012-01-01

    This study examined the role of attitudes against bullying and perceived peer pressure for intervention in explaining defending the victim and passive bystanding behavior in bullying. Participants were 1031 school-age children from two culturally diverse settings, namely Italy and Singapore, which are similar on several dimensions (e.g., quality…

  14. Active Defending and Passive Bystanding Behavior in Bullying: The Role of Personal Characteristics and Perceived Peer Pressure

    Science.gov (United States)

    Pozzoli, Tiziana; Gini, Gianluca

    2010-01-01

    This study examined the role of pro-victim attitudes, personal responsibility, coping responses to observations of bullying, and perceived peer normative pressure in explaining defending the victim and passive bystanding behavior in bullying. A total of 462 Italian early adolescents (mean age = 13.4 years, SD = 9 months) participated in the study.…

  15. Studies of ionising radiation induced bystander effects in 3D artificial tissue system and applications for radiation protection

    International Nuclear Information System (INIS)

    The universality of the target theory of radiation-induced effects is challenged by observations on non-targeted effects such as bystander effects. Essential features of non-targeted effects are that they do not require direct nuclear exposure by radiation and they are particularly significant at low doses. This new evidence suggests a need for a new paradigm in radiation biology. The new paradigm should cover both the classical (targeted) and the non-targeted effects. The bystander effect cannot be comprehensively explained on the basis of a single cell reaction. It is well known that an organism is composed of different cell types that interact as functional units in a way to maintain normal tissue function. Therefore the radiation response is not simply the sum of cellular responses as assumed in classical radiobiology, predominantly from studies using cell cultures. Experimental models, which maintain tissue-like intercellular cell signalling and 3D structure, are essential for proper understanding of the bystander effect. Our work relates to experimentation with novel 3D artificial human tissue systems available from MatTek Corporation (Boston, USA). Air-liquid interface culture technique is used to grow artificial tissues, which allow to model conditions present in vivo. The Gray Cancer Institute (Northwood, UK) charged particle microbeam was used to irradiate tissue samples in a known pattern with a known number of 3He2+ particles or protons. After irradiation, the tissues models were incubated for 3 days, fixed in 10 % NBF, paraffin embedded and then sliced into 5 μm histological sections located at varying distances from the plane of the irradiated cells. We studied in situ apoptosis and markers of differentiation. Significantly elevated bystander induced apoptosis was observed with 3'-OH DNA end-labelling based technique in 3D artificial tissue systems. Our results also suggested an importance of proliferation and differentiation status for bystander

  16. Reciprocal bystander effect between α-irradiated macrophage and hepatocyte is mediated by cAMP through a membrane signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    He, Mingyuan [Institute of Radiation Medicine, Fudan University, No. 2094 Xie-Tu Road, Shanghai 200032 (China); Department of Radiation Oncology, China–Japan Union Hospital of Jilin University, Changchun 130033 (China); Dong, Chen; Xie, Yuexia; Li, Jitao; Yuan, Dexiao; Bai, Yang [Institute of Radiation Medicine, Fudan University, No. 2094 Xie-Tu Road, Shanghai 200032 (China); Shao, Chunlin, E-mail: clshao@shmu.edu.cn [Institute of Radiation Medicine, Fudan University, No. 2094 Xie-Tu Road, Shanghai 200032 (China)

    2014-05-15

    Highlights: • α-Irradiation induced reciprocal effects between macrophage and hepatocyte cells. • cAMP played a protective role in regulating the reverse bystander effect. • cAMP communication contributed to the reciprocal effects via membrane signaling. • p53 was required for cAMP-regulated bystander effect in the recipient cells. - Abstract: Irradiated cells can induce biological effects on vicinal non-irradiated bystander cells, meanwhile the bystander cells may rescue the irradiated cells through a feedback signal stress. To elucidate the nature of this reciprocal effect, we examined the interaction between α-irradiated human macrophage cells U937 and its bystander HL-7702 hepatocyte cells using a cell co-culture system. Results showed that after 6 h of cell co-culture, mitochondria depolarization corresponding to apoptosis was significantly induced in the HL-7702 cells, but the formation of micronuclei in the irradiated U937 cells was markedly decreased compared to that without cell co-culture treatment. This reciprocal effect was not observed when the cell membrane signaling pathway was blocked by filipin that inhibited cAMP transmission from bystander cells to irradiated cells. After treatment of cells with exogenous cAMP, forskolin (an activator of cAMP) or KH-7 (an inhibitor of cAMP), respectively, it was confirmed that cAMP communication from bystander cells to targeted cells could mitigate radiation damage in U739 cells, and this cAMP insufficiency in the bystander cells contributed to the enhancement of bystander apoptosis. Moreover, the bystander apoptosis in HL-7702 cells was aggravated by cAMP inhibition but it could not be evoked when p53 of HL-7702 cells was knocked down no matter of forskolin and KH-7 treatment. In conclusion, this study disclosed that cAMP could be released from bystander HL-7702 cells and compensated to α-irradiated U937 cells through a membrane signaling pathway and this cAMP communication played a profound role in

  17. Experimental verification for in vitro technique confirmation of bystander effect induced by gamma radiation in CHO-K1 cell line; Verificacao experimental para confirmacao da tecnica in vitro do efeito bystander induzido por radiacao gama na linhagem celular CHO-K1

    Energy Technology Data Exchange (ETDEWEB)

    Viana, P.H.L.; Goes, A.M.; Gomes, D.A., E-mail: pedroleroybio@hotmail.com [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Departamento Bioquimica e Imunologia. Lab. de Imunologia Celular e Molecular; Grynberg, S.E., E-mail: seg@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil)

    2013-08-15

    The bystander effect refers to biological responses detected in cells not directly irradiated but influenced, somehow, by signals transmitted from neighboring irradiated cells. These biological responses include sister chromatid exchange, mutations, micronucleus formation, chromosomal aberrations, carcinogenesis, apoptosis and necrosis. Although its existence is unquestionable, the mechanisms involved on triggering the bystander effect are not yet completely elucidated. Previous studies have shown that the bystander effect depends on a large variety of parameters including the radiation dose, the dose rate, the type of radiation and type of cells or tissue. This study aims to confirm the technique previously used in the literature in human cell lines for the bystander effect verification. The results suggest that the working conditions adopted by the group show technical efficiency and enables the reproduction of the bystander effect. (author)

  18. Time-series clustering of gene expression in irradiated and bystander fibroblasts: an application of FBPA clustering

    Directory of Open Access Journals (Sweden)

    Markatou Marianthi

    2011-01-01

    Full Text Available Abstract Background The radiation bystander effect is an important component of the overall biological response of tissues and organisms to ionizing radiation, but the signaling mechanisms between irradiated and non-irradiated bystander cells are not fully understood. In this study, we measured a time-series of gene expression after α-particle irradiation and applied the Feature Based Partitioning around medoids Algorithm (FBPA, a new clustering method suitable for sparse time series, to identify signaling modules that act in concert in the response to direct irradiation and bystander signaling. We compared our results with those of an alternate clustering method, Short Time series Expression Miner (STEM. Results While computational evaluations of both clustering results were similar, FBPA provided more biological insight. After irradiation, gene clusters were enriched for signal transduction, cell cycle/cell death and inflammation/immunity processes; but only FBPA separated clusters by function. In bystanders, gene clusters were enriched for cell communication/motility, signal transduction and inflammation processes; but biological functions did not separate as clearly with either clustering method as they did in irradiated samples. Network analysis confirmed p53 and NF-κB transcription factor-regulated gene clusters in irradiated and bystander cells and suggested novel regulators, such as KDM5B/JARID1B (lysine (K-specific demethylase 5B and HDACs (histone deacetylases, which could epigenetically coordinate gene expression after irradiation. Conclusions In this study, we have shown that a new time series clustering method, FBPA, can provide new leads to the mechanisms regulating the dynamic cellular response to radiation. The findings implicate epigenetic control of gene expression in addition to transcription factor networks.

  19. Genomic instability after targeted irradiation of human lymphocytes: Evidence for inter-individual differences under bystander conditions

    International Nuclear Information System (INIS)

    Environmental 222radon exposure is a human health concern, and many studies demonstrate that very low doses of high LET α-particle irradiation initiate deleterious genetic consequences in both irradiated and non-irradiated bystander cells. One consequence, radiation-induced genomic instability (RIGI), is a hallmark of tumorigenesis and is often assessed by measuring delayed chromosomal aberrations. We utilised a technique that facilitates transient immobilization of primary lymphocytes for targeted microbeam irradiation and have reported that environmentally relevant doses, e.g. a single 3He2+ particle traversal to a single cell, are sufficient to induce RIGI. Herein we sought to determine differences in radiation response in lymphocytes isolated from five healthy male donors. Primary lymphocytes were irradiated with a single particle per cell nucleus. We found evidence for inter-individual variation in radiation response (RIGI, measured as delayed chromosome aberrations). Although this was not highly significant, it was possibly masked by high levels of intra-individual variation. While there are many studies showing a link between genetic predisposition and RIGI, there are few studies linking genetic background with bystander effects in normal human lymphocytes. In an attempt to investigate inter-individual variation in the induction of bystander effects, primary lymphocytes were irradiated with a single particle under conditions where fractions of the population were traversed. We showed a marked genotype-dependent bystander response in one donor after exposure to 15% of the population. The findings may also be regarded as a radiation-induced genotype-dependent bystander effect triggering an instability phenotype.

  20. Molecular Understanding of Growth Inhibitory Effect from Irradiated to Bystander Tumor Cells in Mouse Fibrosarcoma Tumor Model.

    Science.gov (United States)

    Desai, Sejal; Srambikkal, Nishad; Yadav, Hansa D; Shetake, Neena; Balla, Murali M S; Kumar, Amit; Ray, Pritha; Ghosh, Anu; Pandey, B N

    2016-01-01

    Even though bystander effects pertaining to radiation risk assessment has been extensively studied, the molecular players of radiation induced bystander effect (RIBE) in the context of cancer radiotherapy are poorly known. In this regard, the present study is aimed to investigate the effect of irradiated tumor cells on the bystander counterparts in mouse fibrosarcoma (WEHI 164 cells) tumor model. Mice co-implanted with WEHI 164 cells γ-irradiated with a lethal dose of 15 Gy and unirradiated (bystander) WEHI 164 cells showed inhibited tumor growth, which was measured in terms of tumor volume and Luc+WEHI 164 cells based bioluminescence in vivo imaging. Histopathological analysis and other assays revealed decreased mitotic index, increased apoptosis and senescence in these tumor tissues. In addition, poor angiogenesis was observed in these tumor tissues, which was further confirmed by fluorescence imaging of tumor vascularisation and CD31 expression by immuno-histochemistry. Interestingly, the growth inhibitory bystander effect was exerted more prominently by soluble factors obtained from the irradiated tumor cells than the cellular fraction. Cytokine profiling of the supernatants obtained from the irradiated tumor cells showed increased levels of VEGF, Rantes, PDGF, GMCSF and IL-2 and decreased levels of IL-6 and SCF. Comparative proteomic analysis of the supernatants from the irradiated tumor cells showed differential expression of total 24 protein spots (21 up- and 3 down-regulated) when compared with the supernatant from the unirradiated control cells. The proteins which showed substantially higher level in the supernatant from the irradiated cells included diphosphate kinase B, heat shock cognate, annexin A1, angiopoietin-2, actin (cytoplasmic 1/2) and stress induced phosphoprotein 1. However, the levels of proteins like annexin A2, protein S100 A4 and cofilin was found to be lower in this supernatant. In conclusion, our results provided deeper insight about

  1. A Web-Based Sexual Violence Bystander Intervention for Male College Students: Randomized Controlled Trial

    Science.gov (United States)

    Vivolo-Kantor, Alana; Hardin, James; Berkowitz, Alan

    2014-01-01

    Background Bystander intervention approaches offer promise for reducing rates of sexual violence on college campuses. Most interventions are in-person small-group formats, which limit their reach and reduce their overall public health impact. Objective This study evaluated the efficacy of RealConsent, a Web-based bystander approach to sexual violence prevention, in enhancing prosocial intervening behaviors and preventing sexual violence perpetration. Methods A random probability sample of 743 male undergraduate students (aged 18 to 24 years) attending a large, urban university located in the southeastern United States was recruited online and randomized to either RealConsent (n=376) or a Web-based general health promotion program (n=367). Participants were surveyed online at baseline, postintervention, and 6-months postintervention. RealConsent was delivered via a password-protected Web portal that contained six 30-minute media-based and interactive modules covering knowledge of informed consent, communication skills regarding sex, the role of alcohol and male socialization in sexual violence, empathy for rape victims, and bystander education. Primary outcomes were self-reported prosocial intervening behaviors and sexual violence perpetration. Secondary outcomes were theoretical mediators (eg, knowledge, attitudes). Results At 6-month follow-up RealConsent participants intervened more often (P=.04) and engaged in less sexual violence perpetration (P=.04) compared to controls. In addition, RealConsent participants reported greater legal knowledge of sexual assault (Prape myths (Prape victims (Prape attitudes (P<.001), less hostility toward women (P=.01), greater intentions to intervene (P=.04), less hyper-gender ideology (P<.001), less positive outcome expectancies for nonconsensual sex (P=.03), more positive outcome expectancies for intervening (P<.001), and less comfort with other men’s inappropriate behaviors (P<.001). Conclusions Our results support the

  2. Heat and cold acclimation in helium-cold hypothermia in the hamster.

    Science.gov (United States)

    Musacchia, X. J.

    1972-01-01

    A study was made of the effects of acclimation of hamsters to high (34-35 C) and low (4-5 C) temperatures for periods up to 6 weeks on the induction of hypothermia in hamsters. Hypothermia was achieved by exposing hamsters to a helox mixture of 80% helium and 20% oxygen at 0 C. Hypothermic induction was most rapid (2-3 hr) in heat-acclimated hamsters and slowest (6-12 hr) in cold-acclimated hamsters. The induction period was intermediate (5-8 hr) in room temperature nonacclimated animals (controls). Survival time in hypothermia was relatable to previous temperature acclimations. The hypothesis that thermogenesis in cold-acclimated hamsters would accentuate resistance to induction of hypothermia was substantiated.

  3. TELOMERASE ACTIVITY DURING 7, 12-DIMETHYLBENZ [a] ANTHRACENE-INDUCED HAMSTER BUCCAL POUCH CARCINOGENESIS

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To investigate the roles of telomerase activity (TA) in relation to hamster buccal pouch tumor progression. Methods: male hamster were treated three times weekly with 0.5% of 7, 12-dimethyl- benzanthracene (DMBA) over a 15 weeks experimental period. Hamsters were sacrificed at 3, 6, 9, 12 and 15 weeks after treatment. Telomerase activity of hamster buccal pouch tissue were measured along with the analyses of the formation of DMBA-induced hamster buccal pouch tumors. Results: DMBA-induced squamous cell carcinomas were found at the 6th week after dosing. Telomerase activity elevation began at the 3rd week and was increasing to a plateau at the 12th week. Conclusion: Our results show that telomerase activity in the target tissue may be detected at the early stage of the DMBA-induced hamster buccal pouch tumor formation and suggests that telomerase activity may be used as a biomarker for an early clinical detection of buccal pouch cancer.

  4. Alpha-particle-induced bystander effects between zebrafish embryos in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Yum, E.H.W.; Choi, V.W.Y.; Nikezic, D. [Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong); Li, V.W.T.; Cheng, S.H. [Department of Biology and Chemistry, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong); Yu, K.N., E-mail: peter.yu@cityu.edu.h [Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong)

    2009-10-15

    Dechorionaed embryos of the zebrafish, Danio rerio, at 1.5 h post-fertilization (hpf) were irradiated with alpha particles from an {sup 241}Am source. Thin polyallyldiglycol carbonate (PADC) films with a thickness of 16 mum were used as support substrates for holding the embryos and recorded alpha-particle hit positions, and thus enabled calculation of the dose absorbed by the embryos. The irradiated embryos were subsequently incubated with naive (unirradiated) embryos in such a way that the irradiated and naive embryos were spatially separated but the medium was shared. Acridine orange was used to perform in vital staining to show cell deaths in the naive embryos at 24 hpf. Our results gave evidence in supporting the existence of alpha-particle-induced bystander effects between zebrafish embryos in vivo, and a general positive correlation between the cell death signals in the naive embryos and the alpha-particle dose absorbed by the irradiated embryos.

  5. Diffusible Factors Secreted by Glioblastoma and Medulloblastoma Cells Induce Oxidative Stress in Bystander Neural Stem Progenitors.

    Science.gov (United States)

    Sharma, Neha; Colangelo, Nicholas W; de Toledo, Sonia M; Azzam, Edouard I

    2016-08-01

    Harmful effects that alter the homeostasis of neural stem or progenitor cells (NSPs) can affect regenerative processes in the central nervous system. We investigated the effect of soluble factors secreted by control or (137)Cs-γ-irradiated glioblastoma or medulloblastoma cells on redox-modulated endpoints in recipient human NSPs. Growth medium harvested from the nonirradiated brain tumor cells, following 24 h of growth, induced prominent oxidative stress in recipient NSPs as judged by overall increases in mitochondrial superoxide radical levels (p medulloblastoma cells that was more potent at inducing apoptosis in the NSPs than medium from nonirradiated cells (p < .001). The elucidation of such stressful bystander effects provides avenues to understand the biochemical events underlying the development or exacerbation of degenerative outcomes associated with brain cancers. It is also relevant to tissue culture protocols whereby growth medium conditioned by tumor cells is often used to support the growth of stem cells. PMID:27511909

  6. Re-Evaluating Sexual Violence Prevention Through Bystander Education: A Latent Growth Curve Approach.

    Science.gov (United States)

    Shaw, Jessica; Janulis, Patrick

    2016-10-01

    Recently, there has been a call for more advanced analytic techniques in violence against women research, particularly in community interventions that use longitudinal designs. The current study re-evaluates experimental evaluation data from a sexual violence bystander intervention program. Using an exploratory latent growth curve approach, we were able to model the longitudinal growth trajectories of individual participants over the course of the entire study. Although the results largely confirm the original evaluation findings, the latent growth curve approach better fits the demands of "messy" data (e.g., missing data, varying number of time points per participant, and unequal time spacing within and between participants) that are frequently obtained during a community-based intervention. The benefits of modern statistical techniques to practitioners and researchers in the field of sexual violence prevention, and violence against women more generally, are further discussed. PMID:25888503

  7. Diffusible Factors Secreted by Glioblastoma and Medulloblastoma Cells Induce Oxidative Stress in Bystander Neural Stem Progenitors.

    Science.gov (United States)

    Sharma, Neha; Colangelo, Nicholas W; de Toledo, Sonia M; Azzam, Edouard I

    2016-08-01

    Harmful effects that alter the homeostasis of neural stem or progenitor cells (NSPs) can affect regenerative processes in the central nervous system. We investigated the effect of soluble factors secreted by control or (137)Cs-γ-irradiated glioblastoma or medulloblastoma cells on redox-modulated endpoints in recipient human NSPs. Growth medium harvested from the nonirradiated brain tumor cells, following 24 h of growth, induced prominent oxidative stress in recipient NSPs as judged by overall increases in mitochondrial superoxide radical levels (p p21(Waf1) and p27(Kip1), and perturbations in cell cycle progression (p cells to radiation only slightly altered the induced oxidative changes in the bystander NSPs, except for medium from irradiated medulloblastoma cells that was more potent at inducing apoptosis in the NSPs than medium from nonirradiated cells (p cells is often used to support the growth of stem cells.

  8. Space radiation-induced bystander effect: kinetics of biologic responses, mechanisms, and significance of secondary radiations

    International Nuclear Information System (INIS)

    Widespread evidence indicates that exposure of cell cultures to a particles results in significant biological changes in both the irradiated and non-irradiated bystander cells in the population. The induction of non-targeted biological responses in cell cultures exposed to low fluences of high charge (Z) and high energy (E) particles is relevant to estimates of the health risks of space radiation and to radiotherapy. Here, we investigated the mechanisms underlying the induction of stressful effects in confluent normal human fibroblast cultures exposed to low fluences of 1000 MeV/u iron ions (linear energy transfer (LET) 151 keV/μm), 600 MeV/u silicon ions (LET 50 keV/μm) or 290 MeV/u carbon ions (LET 13 keV/μm). We compared the results with those obtained in cell cultures exposed, in parallel, to low fluences of 0.92 MeV/u a particles (LET 109 keV/μm). Induction of DNA damage, changes in gene expression, protein carbonylation and lipid peroxidation during 24 h after exposure of confluent cultures to mean doses as low as 0.2 cGy of iron or silicon ions strongly supported the propagation of stressful effects from irradiated to bystander cells. At a mean dose of 0.2 cGy, only 1 and 3 % of the cells would be targeted through the nucleus by an iron or silicon ion, respectively. Within 24 h post-irradiation, immunoblot analyses revealed significant increases in the levels of phospho-TP53 (serine 15), p21Waf1 (also known as CDKN1A), HDM2, phospho-ERK1/2, protein carbonylation and lipid peroxidation. The magnitude of the responses suggested participation of non-targeted cells in the response. Furthermore, when the irradiated cell populations were subcultured in fresh medium shortly after irradiation, greater than expected increases in the levels of these markers were also observed during 24 h. Together, the results imply a rapidly propagated and persistent bystander effect. In situ analyses in confluent cultures showed 53BP1 foci formation, a marker of DNA damage, in

  9. Cystolithiasis in a Syrian hamster: a different outcome

    Directory of Open Access Journals (Sweden)

    D. Petrini

    2016-08-01

    Full Text Available A 14-month-old intact male Syrian hamster was admitted for lethargy and hematuria. A total body radiographic image and abdominal ultrasonography showed the presence of a vesical calculus. During cystotomy, a sterile urine sample was obtained and sent to the diagnostic laboratory along with the urolith for analysis. Urine culture was found negative for bacterial growth, and the urolith was identified as a calcium-oxalate stone. Diet supplementation with palmitoylethanolamide, glucosamine and hesperidin was adopted the day after discharge. One year follow up revealed no presence of vesical calculi. Although this is the report of a single clinical case, this outcome differs from the results reported in the literature characterized by recurrences after few months. Considering the positive outcome and the beneficial properties of palmitoylethanolamide, glucosamine, and hesperidin, these nutritional elements in Syrian hamsters, are recommended to reduce recurrence after surgical treatment of urolithiasis.

  10. Cystolithiasis in a Syrian hamster: a different outcome.

    Science.gov (United States)

    Petrini, D; Di Giuseppe, M; Deli, G; De Caro Carella, C

    2016-01-01

    A 14-month-old intact male Syrian hamster was admitted for lethargy and hematuria. A total body radiographic image and abdominal ultrasonography showed the presence of a vesical calculus. During cystotomy, a sterile urine sample was obtained and sent to the diagnostic laboratory along with the urolith for analysis. Urine culture was found negative for bacterial growth, and the urolith was identified as a calcium-oxalate stone. Diet supplementation with palmitoylethanolamide, glucosamine and hesperidin was adopted the day after discharge. One year follow up revealed no presence of vesical calculi. Although this is the report of a single clinical case, this outcome differs from the results reported in the literature characterized by recurrences after few months. Considering the positive outcome and the beneficial properties of palmitoylethanolamide, glucosamine, and hesperidin, these nutritional elements in Syrian hamsters, are recommended to reduce recurrence after surgical treatment of urolithiasis. PMID:27540515

  11. Oral implantation of Bacteroides asaccharolyticus and Eikenella corrodens in conventional hamsters.

    OpenAIRE

    Nagahata, T; Kiyoshige, T; Tomono, S; Abe, R; Sasaki, S.; Takazoe, I

    1982-01-01

    Oral implantation of Bacteroides asaccharolyticus 381-R' and Eikenella corrodens 1073S-R, which are highly resistant to streptomycin, was examined in conventional hamsters. The hamsters' first molars were ligatured with cotton threads preimmersed in bacterial suspensions. Bacterial inoculation was performed daily for 1 week, followed by a single weekly inoculation for 7 more weeks. Hamsters were fed Keyes' diet no. 2000 or ordinary powdered diet. Bacterial recovery, gingival histological chan...

  12. Hibernation, stress, intestinal functions, and catecholoamine turnover rate in hamsters and gerbils

    Science.gov (United States)

    Musacchia, X. J.

    1973-01-01

    Bioenergetic studies on hamsters during depressed metabolic states are reported. External support of blood glucose extended the survival times of hibernating animals. Radioresistance increased in hibernating as well as in hypothermic hamsters. Marked changes in hamster catecholamine turnover rates were observed during acclimatization to high temperature stress. High radioresistance levels of the gerbil gastrointestinal system were attributed in part to the ability of the gut to maintain functional integrity.

  13. Photoperiodic regulation of adrenal hormone secretion and aggression in female Syrian hamsters

    OpenAIRE

    Gutzler, Stephanie J.; Karom, Mary; Erwin, W. Daniel; ALBERS, H. Elliott

    2009-01-01

    Seasonal changes in the length of the daily photoperiod induce significant changes in social behavior. Hamsters housed in winter-like short photoperiods (SP) can express significantly higher levels of aggression than hamsters housed in long photoperiods (LP) that mimic summer. The mechanisms responsible for increasing aggressiveness in SP-exposed female hamsters are not well understood but may involve seasonal changes in the endocrine system. In experiment 1, the effects of SP exposure on the...

  14. Bystander effects, genomic instability, adaptive response, and cancer risk assessment for radiation and chemical exposures

    International Nuclear Information System (INIS)

    There is an increased interest in utilizing mechanistic data in support of the cancer risk assessment process for ionizing radiation and environmental chemical exposures. In this regard, the use of biologically based dose-response models is particularly advocated. The aim is to provide an enhanced basis for describing the nature of the dose-response curve for induced tumors at low levels of exposure. Cellular responses that might influence the nature of the dose-response curve at low exposures are understandably receiving attention. These responses (bystander effects, genomic instability, and adaptive responses) have been studied most extensively for radiation exposures. The former two could result in an enhancement of the tumor response at low doses and the latter could lead to a reduced response compared to that predicted by a linear extrapolation from high dose responses. Bystander responses, whereby cells other than those directly traversed by radiation tracks are damaged, can alter the concept of target cell population per unit dose. Similarly, induced genomic instability can alter the concept of total response to an exposure. There appears to be a role for oxidative damage and cellular signaling in the etiology of these cellular responses. The adaptive response appears to be inducible at very low doses of radiation or of some chemicals and reduces the cellular response to a larger challenge dose. It is currently unclear how these cellular toxic responses might be involved in tumor formation, if indeed they are. In addition, it is not known how widespread they are as regards inducing agents. Thus, their impact on low dose cancer risk remains to be established

  15. Contribution of nitric oxide radicals in bystander and adaptive responses induced by heavy ion-beams

    International Nuclear Information System (INIS)

    The purpose of this study was to investigate whether radioadaptive responses were induced after irradiation with accelerated ion beams through nitric oxide-mediated bystander response in cultured cells in vitro and in some organs of mice in vivo. Human non-small cell lung carcinoma cells transfected with wild-type p53 (H1299/wtp53 cells) were used. The cells were irradiated with accelerated neon (400 MeV/u, 31 keV/μm) or iron (500 MeV/u, 200 keV/μm) ion beams. Then, the cells were allowed forming colonies, were cultured for 48 h to obtained samples for Western blot analysis, or were cultured for several weeks to fix mutations in the locus of hprt gene. ICR male mice (Jcl:ICR) were used. The mice were irradiated on 2 days with accelerated carbon ion beams (290 MeV/u, 13 keV/μm) or argon ion beams (500 MeV/u, 90 keV/μm). The intestine and testis were excised 2 days after the last irradiation. These excised tissues were fixed, embedded in paraffin and made of thin-sections on slide glasses. Then the TdT-mediated dUTP-biotin nick end-labeling (TUNEL)- and activated caspase-3-positive cells in the thin-sections of tissues were detected by the immunohistochemical method. A significant reduction of mutation rate of the hprt gene was observed when the cells were challengingly irradiated after the priming irradiation with accelerate neon or iron ion beams. This reduction was partially suppressed by NO radical scavenger, carboxy-PTIO. The bystander-induced apoptotic and activated caspase-3-positive cells were obviously observed in unirradiated intestine and testis when mice were irradiated with carbon or argon ion beams across the upper body. These observations were partially suppressed by carboxy-PTIO into the peritoneal cavity. (author)

  16. Radiation-Induced Bystander Effects in A549 Cells Exposed to 6 MV X-rays.

    Science.gov (United States)

    Yang, Shuning; Xu, Jing; Shao, Weixian; Geng, Chong; Li, Jia; Guo, Feng; Miao, Hui; Shen, Wenbin; Ye, Tao; Liu, Yazhou; Xu, Haiting; Zhang, Xuguang

    2015-07-01

    The aim of the study is to explore the bystander effects in A549 cells that have been exposed to 6MV X-ray. Control group, irradiated group, irradiated conditioned medium (ICM)-received group, and fresh medium group were designed in this study. A549 cells in the logarithmic growth phase were irradiated with 6MV X-ray at 0, 0.5, 1, 1.5, and 2. In ICM-received group, post-irradiation A549 cells were cultured for 3 h and were transferred into non-irradiated A549 cells for further cultivation. Clone forming test was applied to detect the survival fraction of cells. Annexin V-FITC/PI double-staining assay was used to detect the apoptosis of A549 cells 24, 48, 72, and 96 h after 2-Gy 6MV X-ray irradiation, and the curves of apoptosis were drawn. The changes in the cell cycles 4, 48, 72, and 96 h after 2-Gy 6MV X-ray irradiation were detected using PI staining flow cytometry. With the increase of irradiation dose, the survival fraction of A549 cells after the application of 0.5 Gy irradiation was decreasing continuously. In comparison to the control group, the apoptosis rate of the ICM-received group was increased in a time-dependent pattern, with the highest apoptosis rate observed at 72 h (p A549 cell damage, indicating that 6MV X-ray irradiation can induce bystander effect on A549 cells, which reaches a peak at 72 h. PMID:25686868

  17. Inhibition of caries in hamsters treated with staphylococcin 1580.

    OpenAIRE

    Fitzgerald, R J; Morhart, R E; Marquez, C; Adams, B. O.

    1986-01-01

    Littermate hamsters were infected orally with cariogenic Streptococcus mutans NS-50S and maintained on a high-sucrose diet to induce dental caries. Individual groups of animals were treated by single daily instillation of staphylococcin 1580 (100 micrograms) in the cheek pouches. Other groups were treated similarly with bacitracin (60 or 120 U) or saline. After 35 days on the caries test regimen, animals treated with staphylococcin 1580 had 49 or 60% less caries than the saline controls in tw...

  18. Photoperiodic influences on ultradian rhythms of male Siberian hamsters.

    Science.gov (United States)

    Prendergast, Brian J; Zucker, Irving

    2012-01-01

    Seasonal changes in mammalian physiology and behavior are proximately controlled by the annual variation in day length. Long summer and short winter day lengths markedly alter the amplitude of endogenous circadian rhythms and may affect ultradian oscillations, but the threshold photoperiods for inducing these changes are not known. We assessed the effects of short and intermediate day lengths and changes in reproductive physiology on circadian and ultradian rhythms of locomotor activity in Siberian hamsters. Males were maintained in a long photoperiod from birth (15 h light/day; 15 L) and transferred in adulthood to 1 of 7 experimental photoperiods ranging from 14 L to 9 L. Decreases in circadian rhythm (CR) robustness, mesor and amplitude were evident in photoperiods ≤14 L, as were delays in the timing of CR acrophase and expansion of nocturnal activity duration. Nocturnal ultradian rhythms (URs) were comparably prevalent in all day lengths, but 15 L markedly inhibited the expression of light-phase URs. The period (τ'), amplitude and complexity of URs increased in day lengths ≤13 L. Among hamsters that failed to undergo gonadal regression in short day lengths (nonresponders), τ' of the dark-phase UR was longer than in photoresponsive hamsters; in 13 L the incidence and amplitude of light-phase URs were greater in hamsters that did not undergo testicular regression. Day lengths as long as 14 L were sufficient to trigger changes in the waveform of CRs without affecting UR waveform. The transition from a long- to a short-day ultradian phenotype occurred for most UR components at day lengths of 12 L-13 L, thereby establishing different thresholds for CR and UR responses to day length. At the UR-threshold photoperiod of 13 L, differences in gonadal status were largely without effect on most UR parameters.

  19. Circadian arrhythmia dysregulates emotional behaviors in aged Siberian hamsters.

    Science.gov (United States)

    Prendergast, Brian J; Onishi, Kenneth G; Patel, Priyesh N; Stevenson, Tyler J

    2014-03-15

    Emotional behaviors are influenced by the circadian timing system. Circadian disruptions are associated with depressive-like symptoms in clinical and preclinical populations. Circadian rhythm robustness declines markedly with aging and may contribute to susceptibility to emotional dysregulation in aged individuals. The present experiments used a model of chronic circadian arrhythmia generated noninvasively, via a series of circadian-disruptive light treatments, to investigate interactions between circadian desynchrony and aging on depressive- and anxiety-like behaviors, and on limbic neuroinflammatory gene expression that has been linked with emotionality. We also examined whether a social manipulation (group housing) would attenuate effects of arrhythmia on emotionality. In aged (14-18 months of age) male Siberian hamsters, circadian arrhythmia increased behavioral despair and decreased social motivation, but decreased exploratory anxiety. These effects were not evident in younger (5-9 months of age) hamsters. Social housing (3-5 hamsters/cage) abolished the effects of circadian arrhythmia on emotionality. Circadian arrhythmia alone was without effect on hippocampal or cortical interleukin-1β (IL-1β) and indoleamine 2,3-dioxygenase (Ido) mRNA expression in aged hamsters, but social housing decreased hippocampal IL-1β and Ido mRNAs. The data demonstrate that circadian disruption can negatively impact affective state, and that this effect is pronounced in older individuals. Although clear associations between circadian arrhythmia and constitutive limbic proinflammatory activity were not evident, the present data suggest that social housing markedly inhibits constitutive hippocampal IL-1β and Ido activity, which may contribute to the ameliorating effects of social housing on a number of emotional behaviors.

  20. Antibody Prophylaxis and Therapy against Nipah Virus Infection in Hamsters

    OpenAIRE

    Guillaume, V; Contamin, H.; Loth, P.; Grosjean, I.; Courbot, M. C. Georges; Deubel, V.; Buckland, R; Wild, T F

    2006-01-01

    Nipah virus (NiV), a member of the Paramyxoviridae family, causes a zoonotic infection in which the reservoir, the fruit bat, may pass the infection to pigs and eventually to humans. In humans, the infection leads to encephalitis with >40 to 70% mortality. We have previously shown that polyclonal antibody directed to either one of two glycoproteins, G (attachment protein) or F (fusion protein), can protect hamsters from a lethal infection. In the present study, we have developed monoclonal an...

  1. Stochastic models of the bystander effect and of transmissible genomic instability: implications for mechanisms and low dose risks

    Science.gov (United States)

    Little, M. P.

    Bystander effects following exposure to α -particles have been observed in C3H 10T cells and in other experimental systems, and imply that linearly extrapolating low dose risks from high-dose data might materially underestimate risk. In many experimental systems there is evidence of saturation of dose response that would be expected from the bystander effect. The ratio of lung cancer risk among persons exposed to low and high doses of radon daughters is 2.4 -- 4.0, with an upper 95% confidence limit of about 14. Assuming the bystander effect observed in the C3H 10T data applies to human lung cells in vivo, the epidemiological data imply that the number of neighbouring cells that can contribute to the bystander effect is between 0 and 1, with an upper 95% confidence limit of about 7. As a consequence, the bystander effect observed in the C3H 10T system probably does not play a large part in the process of radon-induced lung carcinogenesis in humans. Other experimental data relating to the bystander effect after α -particle exposure are surveyed; some of these data are more compatible with the epidemiological data. Three models of genomic instability recently developed by Little and Wright (Math. Biosci. 2003;183:111-34), with two, three and five stages, are compared with the four-stage model proposed by Luebeck and Moolgavkar (PNAS 2002;99:15095-100) and the two-stage model of Nowak et al. (PNAS 2002;99:16226-31). All models are fitted to SEER colon cancer data. Although the five-stage model of Little and Wright (2003) provides the best fit, it is not much superior to that of the model of Nowak et al. (2002) or the two- and three-stage models of Little and Wright (2003). The fit of the model of Luebeck and Moolgavkar (2002) is somewhat worse than these three, particularly for females under the age of 40. Comparison of the predictions of the two-stage models of Little and Wright (2003) and Nowak (2002) with patterns of excess risk in the Japanese atomic bomb

  2. Goitre and wasting induced in hamsters by hexachlorobenzene

    International Nuclear Information System (INIS)

    Male Syrian hamsters were treated with hexachlorobenzene (HCB) in their diet at levels of 100 ppm for 28 weeks, 200 ppm for 18 and 28 weeks, and 500 ppm for 6 weeks. All treatments caused at least a 2.5- to 3-fold increase in thyroid size, mainly by enlargement of some follicles. Serum thyroxine (T4) levels were unchanged, whereas levels of triiodothyronine (T3) eventually became depressed by >60%. Uptake of 131I into thyroids was induced approximately 3-fold when estimated after feeding HCB (500 ppm) for 3 or 6 weeks. Hamsters also lost weight by depletion of adipose tissue, leading to 50% mortality in longer experiments. Results were distinct from the effects of the known antithyroid agent 3-aminotriazole or amitrole (200 ppm for 28 weeks), which did not affect survival and although causing thyroid enlargement depressed serum T4 and significantly elevated T3. The effects of HCB in hamsters were also different from those in rats (500 ppm HCB for 6 weeks) in which there was only a small increase in thyroid size (1.3-fold), serum levels of T3 were only slightly depressed but T4 levels were reduced by 74%. These studies are discussed with reference to the effects of other polyhalogenated aromatic chemicals on the thyroid, serum thyroid hormone levels and lethality. (orig.)

  3. Effects of hyperthermia on the hamster immune system

    International Nuclear Information System (INIS)

    In previous studies, the authors have shown that hyperthermia can enhance antibody-complement chytotoxicity of hamster and human tumor cells. Moreover, whole body microwave exposure of hamsters resulted in activation of peritoneal macrophages to a viricidal state and transient suppression of natural killer (NK) cell activity. In this study, the authors compare the effects of whole body heating by microwaves or by an environmental chamber (hot air) on the hamster immune system. Microwave exposure (25mW/cm/sup 2/; 1 hr) caused viricidal activation of peritoneal macrophages which resulted in restriction of vaccinia and vesicular stomatitis virs (VSV) growth. However, heating in an environmental chamber (410C; 1 hr) did not activate macrophages to a viricidal state. Both microwave and hot air hyperthermia caused significant augmentation of antibody producing spleen cell response to sheep red blood cells (SRBC), using the Jerne hymolytic plaque assay, four days post exposure and immunization with SRBC. Natural killer spleen cell cytotoxicity was suppressed by microwave and hot air hyperthermia showing that NK lymphocytes are extremely sensitive to changes in temperature. These alterations in cellular immune response due to hyperthermia could be of significance in treatment of tumors and viral infections

  4. Female-biased anorexia and anxiety in the Syrian hamster.

    Science.gov (United States)

    Shannonhouse, John L; Fong, Li An; Clossen, Bryan L; Hairgrove, Ross E; York, Daniel C; Walker, Benjamin B; Hercules, Gregory W; Mertesdorf, Lauren M; Patel, Margi; Morgan, Caurnel

    2014-06-22

    Anorexia and anxiety cause significant mortality and disability with female biases and frequent comorbidity after puberty, but the scarcity of suitable animal models impedes understanding of their biological underpinnings. It is reported here that in adult or weanling Syrian hamsters, relative to social housing (SH), social separation (SS) induced anorexia characterized as hypophagia, weight loss, reduced adiposity, and hypermetabolism. Following anorexia, SS increased reluctance to feed, and thigmotaxis, in anxiogenic environments. Importantly, anorexia and anxiety were induced post-puberty with female biases. SS also reduced hypothalamic corticotrophin-releasing factor mRNA and serum corticosteroid levels assessed by RT-PCR and RIA, respectively. Consistent with the view that sex differences in adrenal suppression contributed to female biases in anorexia and anxiety by disinhibiting neuroimmune activity, SS elevated hypothalamic interleukin-6 and toll-like receptor 4 mRNA levels. Although corticosteroids were highest during SH, they were within the physiological range and associated with juvenile-like growth of white adipose, bone, and skeletal muscle. These results suggest that hamsters exhibit plasticity in bioenergetic and emotional phenotypes across puberty without an increase in stress responsiveness. Thus, social separation of hamsters provides a model of sex differences in anorexia and anxiety during adulthood and their pathogeneses during adolescence.

  5. Experience-independent development of the hamster circadian visual system.

    Directory of Open Access Journals (Sweden)

    August Kampf-Lassin

    Full Text Available Experience-dependent functional plasticity is a hallmark of the primary visual system, but it is not known if analogous mechanisms govern development of the circadian visual system. Here we investigated molecular, anatomical, and behavioral consequences of complete monocular light deprivation during extended intervals of postnatal development in Syrian hamsters. Hamsters were raised in constant darkness and opaque contact lenses were applied shortly after eye opening and prior to the introduction of a light-dark cycle. In adulthood, previously-occluded eyes were challenged with visual stimuli. Whereas image-formation and motion-detection were markedly impaired by monocular occlusion, neither entrainment to a light-dark cycle, nor phase-resetting responses to shifts in the light-dark cycle were affected by prior monocular deprivation. Cholera toxin-b subunit fluorescent tract-tracing revealed that in monocularly-deprived hamsters the density of fibers projecting from the retina to the suprachiasmatic nucleus (SCN was comparable regardless of whether such fibers originated from occluded or exposed eyes. In addition, long-term monocular deprivation did not attenuate light-induced c-Fos expression in the SCN. Thus, in contrast to the thalamocortical projections of the primary visual system, retinohypothalamic projections terminating in the SCN develop into normal adult patterns and mediate circadian responses to light largely independent of light experience during development. The data identify a categorical difference in the requirement for light input during postnatal development between circadian and non-circadian visual systems.

  6. Learned magnetic compass orientation by the Siberian hamster, Phodopus sungorus

    Energy Technology Data Exchange (ETDEWEB)

    Deutschlander, Mark E.; Freake, Michael J.; Borland, Christopher; Phillips, John B.; Madden, R C.; Anderson, Larry E.; Wilson, B W.

    2003-04-01

    Magnetic orientation has been demonstrated in Siberian hamsters, Phodopus sungorus. The behavior, using a nest building assay, shows a directional preference in nest position and appears in this animal to be a learned behavior. Hamsters were housed prior to testing in rectangular cages aligned along perpendicular axes. When subsequently tested in a radially-symmetrical arena, the hamsters positioned their nests in a bimodal distribution that coincided with the magnetic direction of the long-axis of the holding cages. In addition, results are presented that illustrate some of the factors that can influence behavioral responses to the magnetic field. In particular for P. sungorus, holding conditions prior to testing and the presence of non-magnetic cues may influence the strength and expression of magnetic orientation. Failure to consider these and other factors may help to explain why previous attempts to demonstrate magnetic orientation in a number of rodent species have failed or, when positive results have been obtained, have been difficult to replicate in other laboratories.

  7. Teratogenicity and embryotoxicity of nickel carbonyl in Syrian hamsters

    Energy Technology Data Exchange (ETDEWEB)

    Sunderman, F.W. Jr.; Shen, S.K.; Reid, M.C.; Allpass, P.R.

    1980-01-01

    Nickel carbonyl was administered to groups of pregnant hamsters by inhalation on days 4, 5, 6, 7, or 8 of gestation. The dams were killed on day 15 of gestation, and the fetuses were examined for malformations. Exposure to Ni(CO)/sub 4/ on days 4 or 5 of gestation resulted in malformation in 5.5% and 5.8% of the progeny, respectively. Progeny included 9 fetuses with cystic lungs, 7 fetuses with exencephaly, 1 fetus with exencephaly plus fused rib and 1 fetus with anophthalmia plus cleft palate. Hemorrhages into serious cavities were found. In progeny of dams exposed to Ni(CO)/sub 4/ on days 6 or 7 of gestation, there was 1 fetus with fused ribs and there were 2 fetuses with hydronephrosis. In another experiment, pregnant hamsters were exposed to inhalation of Ni(CO)/sub 4/ on day 5 of gestation; these dams were permitted to deliver their litters and to nurse their pups. There was no significant difference in the average number of live pups in the Ni(CO)/sub 4/-exposed litters compared to control litters. Neonatal mortality was increased in Ni(CO)/sub 4/-exposed litters. This study demonstrates that Ni(CO)/sub 4/ is teratogenic and embryotoxic in Syrian hamsters.

  8. Blame Conformity: Innocent Bystanders Can Be Blamed for a Crime as a Result of Misinformation from a Young, but Not Elderly, Adult Co-Witness.

    Directory of Open Access Journals (Sweden)

    Craig Thorley

    Full Text Available This study examined whether or not exposing an eyewitness to a co-witness statement that incorrectly blames an innocent bystander for a crime can increase the likelihood of the eyewitness subsequently blaming the innocent bystander for the crime. It also examined whether or not the perceived age of the co-witness influences this effect. Participant eyewitnesses first watched a video of a crime featuring a perpetrator and an innocent bystander. They then read one of six bogus co-witness statements about the crime. All were presented as having been written by a female co-witness and they differed in terms of her age (young adult or elderly and who she blamed for the crime (the perpetrator, the innocent bystander, or nobody. One week later the participants were asked who committed the crime. When the young adult co-witness had blamed the innocent bystander just over 40% of participants subsequently did the same. Few participants (less than 8% in the other conditions subsequently blamed the innocent bystander. The elderly co-witness was also rated as less credible, less competent, and less accurate than the younger co-witness suggesting eyewitnesses were less likely to be influenced by her incorrect statement as they perceived her to be a less reliable source of information. The applied implications of these findings are discussed.

  9. Triterpenic Acids Present in Hawthorn Lower Plasma Cholesterol by Inhibiting Intestinal ACAT Activity in Hamsters

    Directory of Open Access Journals (Sweden)

    Yuguang Lin

    2011-01-01

    Full Text Available Hawthorn (Crataegus pinnatifida is an edible fruit used in traditional Chinese medicine to lower plasma lipids. This study explored lipid-lowering compounds and underlying mechanisms of action of hawthorn. Hawthorn powder extracts inhibited acylCoA:cholesterol acyltransferase (ACAT activity in Caco-2 cells. The inhibitory activity was positively associated with triterpenic acid (i.e., oleanolic acid (OA and ursolic acid (UA contents in the extracts. Cholesterol lowering effects of hawthorn and its potential additive effect in combination with plant sterol esters (PSE were further studied in hamsters. Animals were fed a semi-synthetic diet containing 0.08% (w/w cholesterol (control or the same diet supplemented with (i 0.37% hawthorn dichloromethane extract, (ii 0.24% PSE, (iii hawthorn dichloromethane extract (0.37% plus PSE (0.24% or (iv OA/UA mixture (0.01% for 4 weeks. Compared to the control diet, hawthorn, PSE, hawthorn plus PSE and OA/UA significantly lowered plasma non-HDL (VLDL + LDL cholesterol concentrations by 8%, 9%, 21% and 6% and decreased hepatic cholesterol ester content by 9%, 23%, 46% and 22%, respectively. The cholesterol lowering effects of these ingredients were conversely associated with their capacities in increasing fecal neutral sterol excretion. In conclusion, OA and UA are responsible for the cholesterol lowering effect of hawthorn by inhibiting intestinal ACAT activity. In addition, hawthorn and particularly its bioactive compounds (OA and UA enhanced the cholesterol lowering effect of plant sterols.

  10. Androgen dependence in hamsters: overdose, tolerance, and potential opioidergic mechanisms.

    Science.gov (United States)

    Peters, K D; Wood, R I

    2005-01-01

    Anabolic steroids are drugs of abuse. However, the potential for steroid reward and addiction remains largely unexplored. This study used i.c.v. testosterone self-administration and controlled infusions of testosterone or vehicle in hamsters to explore central mechanisms of androgen overdose. Forty-two hamsters used nose-pokes to self-administer 1 microg/microl testosterone i.c.v. 4 h/day in an operant chamber. During 1-56 days of androgen self-administration, 10 (24%) hamsters died. Deaths correlated with peak daily intake of testosterone. Of the hamsters that self-administered a peak intake of testosterone intake peaked at 20-60 microg/day. Only 30% (three of 10) survived when daily testosterone intake exceeded 60 microg/day. Deaths are not due to volume or vehicle because i.c.v. infusions of 80 mul vehicle had no effect. Testosterone overdose resembles opiate intoxication. When male hamsters received infusions of 40 microg testosterone, locomotion (25.1+/-18.8 grid-crossings/10 min), respiration (72.7+/-5.4 breaths/min) and body temperature (33.5+/-0.4 degrees C) were significantly reduced, compared with males receiving vehicle infusions (186.1+/-8.1 crossings/10 min, 117.6+/-1.0 breaths/min, 35.9+/-0.1 degrees C, Ptestosterone infusion. After 15 days, locomotion (170.2+/-6.3 crossings), respiration (118.4+/-1.3 breaths/min), and body temperature (35.3+/-0.3 degrees C) in testosterone-infused males were equivalent to that in vehicle controls (P>0.05). The depressive effects of testosterone infusion are blocked by the opioid antagonist, naltrexone. With naltrexone pre-treatment (10 mg/kg s.c.), locomotion (183.7+/-1.8 crossings/10 min), respiration (116.9+/-0.3 breaths/min), and body temperature (36.1+/-0.4 degrees C) during testosterone infusion were equivalent to vehicle controls. Likewise, naltrexone prevents the reinforcing effects of i.c.v. testosterone self-administration. These results indicate that testosterone at high doses causes central autonomic

  11. Engaging Active Bystanders in Mass Casualty Events and Other Life-Threatening Emergencies: A Pilot Training Course Demonstration.

    Science.gov (United States)

    Smith, Tracey O; Baker, Susan D; Roberts, Kathryn; Payne, Skip A

    2016-04-01

    Emerging research indicates the critical role members of the public can play in saving lives and reducing morbidity at the scene in the immediate aftermath of a disaster. It is anticipated that with training, more members of the public will be ready and able to assist should they be present at mass casualty events or other circumstances in which there are serious injuries or potential loss of life. This article describes a training course developed by multiple federal and nonfederal partners aimed at preparing the public to become "active bystanders" followed by a pilot demonstration project conducted by Medical Reserve Corps Units. The outcomes of the project indicated that the training was comprehensive and appropriate for members of the public with little or no first aid knowledge. National availability of the "Becoming an Active Bystander" training course is currently being planned. PMID:26841861

  12. Developmental Changes in the ECG of a Hamster Model of Muscular Dystrophy and Heart Failure

    Directory of Open Access Journals (Sweden)

    Thomas Gerard Hampton

    2012-05-01

    Full Text Available Aberrant autonomic signaling is being increasingly recognized as an important symptom in neuromuscular disorders. The delta-sarcoglycan-deficient BIO TO-2 hamster is recognized as a good model for studying mechanistic pathways and sequelae in muscular dystrophy and heart failure, including autonomic nervous system dysfunction. Recent studies using the TO-2 hamster model have provided promising preclinical results demonstrating the efficacy of gene therapy to treat skeletal muscle weakness and heart failure. Methods to accelerate preclinical testing of gene therapy and new drugs for neuromuscular diseases are urgently needed. The purpose of this investigation was to demonstrate a rapid non-invasive screen for characterizing the autonomic nervous system imbalance in dystrophic TO-2 hamsters. Electrocardiograms were recorded non-invasively in conscious ~9-month old TO-2 hamsters (n=10 and non-myopathic F1B control hamsters (n=10. Heart rate was higher in TO-2 hamsters than controls (453 ± 12 bpm vs. 311 ± 25 bpm, P<0.01. Time domain heart rate variability, an index of parasympathetic tone, was lower in TO-2 hamsters (12.2 ± 3.7 bpm vs. 38.2 ± 6.8, P<0.05, as was the coefficient of variance of the RR interval (2.8 ± 0.9 % vs. 16.2 ± 3.4 %, P<0.05 compared to control hamsters. Power spectral analysis demonstrated reduced high frequency and low frequency contributions, indicating autonomic imbalance with increased sympathetic tone and decreased parasympathetic tone in dystrophic TO-2 hamsters. Similar observations in newborn hamsters indicate autonomic nervous dysfunction may occur quite early in life in neuromuscular diseases. Our findings of autonomic abnormalities in newborn hamsters with a mutation in the delta-sarcoglycan gene suggest approaches to correct modulation of the heart rate as prevention or therapy for muscular dystrophies.

  13. The presence of opioidergic pinealocytes in the pineal gland of the European hamster (Cricetus cricetus): an immunocytochemical study

    DEFF Research Database (Denmark)

    Coto-Montes, A.; Masson-Pévet, M.; Pévet, P.;

    1994-01-01

    Neurobiologi, pineal gland, leu-enkephalin, Met-enkephalin, synaptic contacts, paracrine regulation, European hamster, cricetus cricetus (rodents)......Neurobiologi, pineal gland, leu-enkephalin, Met-enkephalin, synaptic contacts, paracrine regulation, European hamster, cricetus cricetus (rodents)...

  14. Radiation-induced bystander effects: Are they good bad or both?; Les nouvelles orientations en radiobiologie et radiopathologie

    Energy Technology Data Exchange (ETDEWEB)

    Le Guen, B.; Lallemand, J. [Electricite de France (EDF), 75 - Paris (France); Averbeck, D. [Institut Curie, 75 - Paris (France); Chetioui, A. [Paris-6 Univ., 75 (France); Gardes-Albert, M. [Paris-5 Univ., 75 (France); Mothersill, C. [Mc Master Univ., Hamilton (Canada); Gourmelon, P.; Benderitter, M. [Institut de Radioprotection et de Surete Nucleaire, 92 - Clamart (France); Chevillard, S.; Martin, M. [CEA Fontenay-aux-Roses, Dir. des sciences du vivant, 92 (France); Verrelle, P. [Centre Jean-Perrin, 63 - Clermont-Ferrand (France)

    2004-07-01

    The different contributions are as follow: the current events on the cellular responses to irradiation ( part one and two); From physico-chemistry to radiobiology: new knowledge (part one and two); Radiation-induced bystander effects: are they good bad or both; recognition of the multi visceral failure in the acute irradiation syndrome; integrated approach of the tissue carcinogenesis: differential effect sane tissue-tumoral tissue; differential diagnosis of thyroid cancers by the transcriptoma analysis. (N.C.)

  15. Perceptions of pesticides exposure risks by operators, workers, residents and bystanders in Greece, Italy and the UK

    International Nuclear Information System (INIS)

    The EU Directive on the sustainable use of pesticides (EU128/2009/EC) requires European Member States to develop training activities targeting occupational exposure to pesticides, and communication material aimed at residents and bystanders. Risk perceptions, knowledge and attitudes associated with passive and occupational exposure to pesticide potentially influence the extent to which different stakeholders adopt self-protective behaviour. A methodology for assessing the link between attitudes, adoption of self-protective behaviours and exposure was developed and tested. A survey was implemented in the Greece, Italy and the UK, and targeted stakeholders associated with pesticide exposure linked to orchards, greenhouse crops and arable crops respectively. The results indicated that the adoption of protective measures is low for residents and bystanders, with the exception of residents in Greece, when compared to operators and workers, who tend to follow recommended safety practices. A regression analysis was used to examine the factors affecting the probability of adopting protective measures as well the as the level of exposure in the case of operators and workers where data are available. The results indicate that the likelihood of engaging in self-protective behaviour is not significantly affected by perceptions of own health being affected by pesticides for residents and bystanders. However, operators who perceive that their heath has been negatively affected by the use of pesticides are found to be more likely to adopt self-protective behaviours. Gender and country differences, in perceptions, attitudes and self-protection are also observed. Recommendations for improved communication, in particular for vulnerable groups, are provided. - Highlights: • Perceptions of risks associated with pesticide exposure were assessed • Surveys were conducted in Greece, Italy and the UK targeting vulnerable stakeholders • Perceptions of risk were associated with

  16. Perceptions of pesticides exposure risks by operators, workers, residents and bystanders in Greece, Italy and the UK

    Energy Technology Data Exchange (ETDEWEB)

    Remoundou, K.; Brennan, M. [Food and Society Group, Centre for Rural Economy, School of Agriculture, Food and Rural Development, Newcastle University, Newcastle Upon Tyne NE19 1AA (United Kingdom); Sacchettini, G. [Opera Research Centre, Università Cattolica del Sacro Cuore di Piacenza, 29100 Piacenza (Italy); Panzone, L. [Food and Society Group, Centre for Rural Economy, School of Agriculture, Food and Rural Development, Newcastle University, Newcastle Upon Tyne NE19 1AA (United Kingdom); Butler-Ellis, M.C. [Silsoe Spray Applications Unit, NIAB, Building 42, Wrest Park, Silsoe, Bedford MK45 4HP (United Kingdom); Capri, E. [Opera Research Centre, Università Cattolica del Sacro Cuore di Piacenza, 29100 Piacenza (Italy); Charistou, A.; Chaideftou, E. [Benaki Phytopathological Institute, 8 Stefanou Delta Street, Kifissia, Athens 14561 (Greece); Gerritsen-Ebben, M.G. [TNO Innovation for Life, Utrechtseweg 48, 3704 HE Zeist (Netherlands); Machera, K. [Benaki Phytopathological Institute, 8 Stefanou Delta Street, Kifissia, Athens 14561 (Greece); Spanoghe, P. [Department of Crop Protection, Ghent University, Coupure Links 653, B-9000 Ghent (Belgium); Glass, R. [Food and Environmental Research Agency, Sand Hutton, York Y0411LZ (United Kingdom); Marchis, A. [Opera Research Centre, Università Cattolica del Sacro Cuore di Piacenza, 29100 Piacenza (Italy); Doanngoc, K. [Department of Crop Protection, Ghent University, Coupure Links 653, B-9000 Ghent (Belgium); Hart, A. [Food and Environmental Research Agency, Sand Hutton, York Y0411LZ (United Kingdom); Frewer, L.J., E-mail: Lynn.Frewer@newcastle.ac.uk [Food and Society Group, Centre for Rural Economy, School of Agriculture, Food and Rural Development, Newcastle University, Newcastle Upon Tyne NE19 1AA (United Kingdom)

    2015-02-01

    The EU Directive on the sustainable use of pesticides (EU128/2009/EC) requires European Member States to develop training activities targeting occupational exposure to pesticides, and communication material aimed at residents and bystanders. Risk perceptions, knowledge and attitudes associated with passive and occupational exposure to pesticide potentially influence the extent to which different stakeholders adopt self-protective behaviour. A methodology for assessing the link between attitudes, adoption of self-protective behaviours and exposure was developed and tested. A survey was implemented in the Greece, Italy and the UK, and targeted stakeholders associated with pesticide exposure linked to orchards, greenhouse crops and arable crops respectively. The results indicated that the adoption of protective measures is low for residents and bystanders, with the exception of residents in Greece, when compared to operators and workers, who tend to follow recommended safety practices. A regression analysis was used to examine the factors affecting the probability of adopting protective measures as well the as the level of exposure in the case of operators and workers where data are available. The results indicate that the likelihood of engaging in self-protective behaviour is not significantly affected by perceptions of own health being affected by pesticides for residents and bystanders. However, operators who perceive that their heath has been negatively affected by the use of pesticides are found to be more likely to adopt self-protective behaviours. Gender and country differences, in perceptions, attitudes and self-protection are also observed. Recommendations for improved communication, in particular for vulnerable groups, are provided. - Highlights: • Perceptions of risks associated with pesticide exposure were assessed • Surveys were conducted in Greece, Italy and the UK targeting vulnerable stakeholders • Perceptions of risk were associated with

  17. Bystander CD8 T-Cell-Mediated Demyelination is Interferon-γ-Dependent in a Coronavirus Model of Multiple Sclerosis

    OpenAIRE

    Dandekar, Ajai A.; Anghelina, Daniela; Perlman, Stanley

    2004-01-01

    Mice infected with the coronavirus mouse hepatitis virus, strain JHM (JHM) develop a disease that shares many histological characteristics with multiple sclerosis. We previously demonstrated that JHM-infected mice that only have CD8 T cells specific for an epitope not in the virus develop demyelination on specific activation of these cells. Herein we show that this process of bystander T-cell-mediated demyelination is interferon-γ (IFN-γ)-dependent. The absence of IFN-γ abrogated demyelinatio...

  18. Things Chinese.

    Science.gov (United States)

    Law, Yip Wang

    Presented in this booklet are brief descriptions of items and activities that are symbolic of Chinese culture. Some of the items and activities described include a traditional Chinese child's outfit, dolls, sandalwood fans, writing and printing materials and techniques, toys and crafts, a Chinese abacus, and eating utensils. Several recipes for…

  19. Radiation-induced bystander effects and adaptive responses--the Yin and Yang of low dose radiobiology?

    Energy Technology Data Exchange (ETDEWEB)

    Mothersill, Carmel [Medical Physics and Applied Radiation Sciences Unit, McMaster University, Hamilton, Ont., L8S 4K1 (Canada)]. E-mail: mothers@mcmaster.ca; Seymour, Colin [Medical Physics and Applied Radiation Sciences Unit, McMaster University, Hamilton, Ont., L8S 4K1 (Canada)]. E-mail: seymouc@mcmaster.ca

    2004-12-02

    Our current knowledge of the mechanisms underlying the induction of bystander effects by low doses of high or low LET ionizing radiation is reviewed. The question of what actually constitutes a protective effect is discussed in the context of adaptive (often referred to as hormetic or protective) responses. Finally the review considers critically, how bystander effects may be related to observed adaptive responses or other seemingly protective effects of low doses exposures. Bystander effects induce responses at the tissue level, which are similar to generalized stress responses. Most of the work involving low LET radiation exposure discussed in the existing literature measures a death response. Since many cell populations carry damaged cells without being exposed to radiation (so-called 'background damage'), it is possible that low doses exposures cause removal of cells carrying potentially problematic lesions, prior to exposure to radiation. This mechanism could lead to the production of 'U-shaped' or hormetic dose-response curves. The level of adverse, adaptive or apparently beneficial response will be related to the background damage carried by the original cell population, the level of organization at which damage or harm are scored and the precise definition of 'harm'. This model may be important when attempting to predict the consequences of mixed exposures involving low doses of radiation and other environmental stressors.

  20. Workplace mobbing and bystanders' helping behaviour towards victims: the role of gender, perceived responsibility and anticipated stigma by association.

    Science.gov (United States)

    Mulder, Roelie; Pouwelse, Mieneke; Lodewijkx, Hein; Bolman, Catherine

    2014-08-01

    We examined victims' perceived responsibility and bystanders' anticipated risk of being victimized themselves when others associate them with the victim (stigma by association, SBA) as possible antecedents of bystanders' helping behaviour towards a victim of workplace mobbing, and explored the effects of gender. Guided by the attribution model of social conduct (Weiner, 2006), a 2 × 2 vignette experiment was conducted. Participants were Dutch regional government employees (N = 161). Path analyses generally supported the hypotheses, but showed different results for women and men. In the strong (Vs. weak) responsibility condition, women reported less sympathy and more anger and men only more anger, which resulted in lower helping intention. Additionally, for men the results showed an unexpected direct positive effect of responsibility on helping intention. Furthermore, in the strong SBA condition, women and men reported more fear and men, unexpectedly, more anger. Consequently, helping intention decreased. The findings on gender are discussed in the context of social role theory, gender and emotion. Our findings suggest that to prevent and tackle mobbing, organizations and professionals should be aware of the attributional and emotional processes and gender differences in bystanders' helping behaviour. PMID:24990642

  1. Increased frequency of spontaneous neoplastic transformation in progeny of bystander cells from cultures exposed to densely ionizing radiation.

    Directory of Open Access Journals (Sweden)

    Manuela Buonanno

    Full Text Available An increased risk of carcinogenesis caused by exposure to space radiation during prolonged space travel is a limiting factor for human space exploration. Typically, astronauts are exposed to low fluences of ionizing particles that target only a few cells in a tissue at any one time. The propagation of stressful effects from irradiated to neighboring bystander cells and their transmission to progeny cells would be of importance in estimates of the health risks of exposure to space radiation. With relevance to the risk of carcinogenesis, we investigated, in model C3H 10T½ mouse embryo fibroblasts (MEFs, modulation of the spontaneous frequency of neoplastic transformation in the progeny of bystander MEFs that had been in co-culture 10 population doublings earlier with MEFs exposed to moderate doses of densely ionizing iron ions (1 GeV/nucleon or sparsely ionizing protons (1 GeV. An increase (P<0.05 in neoplastic transformation frequency, likely mediated by intercellular communication through gap junctions, was observed in the progeny of bystander cells that had been in co-culture with cells irradiated with iron ions, but not with protons.

  2. Monitoring of bystander effect of herpes simplex virus thymidine kinase/acyclovir system using fluorescence resonance energy transfer technique.

    Science.gov (United States)

    Xiong, Tao; Li, Yongjun; Ni, Fenge; Zhang, Feng

    2012-02-01

    Cytotoxic gene therapy mediated by gene transfer of the herpes simplex virus thymidine kinase (HSV-tk) gene followed by acyclovir (ACV) treatment has been reported to inhibit malignant tumor growth in a variety of studies. The magnitude of "bystander effect" is an essential factor for this anti-tumor approach in vivo. However, the mechanism by which HSV-tk/ACV brings "bystander effect" is poorly understood. In this report, the plasmid CD3 (ECFP-CRS-DsRed) and TK-GFP were transferred to the human adenoid cystic carcinoma line ACC-M cell line. The CD3-expressing cells apoptosis was monitored using fluorescence resonance energy transfer (FRET) technique. First, CD3 and TK-GFP co-expressing ACC-M cells apoptosis was monitored using FRET technique. The apoptosis was induced by ACV and initiated by caspase3. The FRET efficient was remarkably decreased and then disappeared during cellular apoptosis, which indicated that the TK-GFP expressing ACC-M cells apoptosis, induced by ACV, was via a caspase3-dependent pathway. Secondly, CD3 and TK-GFP mixed expressing ACC-M cells apoptosis, induced by ACV, were monitored using FRET technique. The apoptotic phenomena appeared in the CD3-expressing ACC-M cells. The results show that HSV-tk/ACV system killed ACC-M cells using its bystander effect. These results confirm that HSV-tk/ACV system is potential for cancer gene therapy.

  3. A Lethal Disease Model for Hantavirus Pulmonary Syndrome in Immunosuppressed Syrian Hamsters Infected with Sin Nombre Virus

    OpenAIRE

    Brocato, Rebecca L.; Hammerbeck, Christopher D.; Bell, Todd M.; Wells, Jay B.; Queen, Laurie A.; Hooper, Jay W.

    2014-01-01

    Sin Nombre virus (SNV) is a rodent-borne hantavirus that causes hantavirus pulmonary syndrome (HPS) predominantly in North America. SNV infection of immunocompetent hamsters results in an asymptomatic infection; the only lethal disease model for a pathogenic hantavirus is Andes virus (ANDV) infection of Syrian hamsters. Efforts to create a lethal SNV disease model in hamsters by repeatedly passaging virus through the hamster have demonstrated increased dissemination of the virus but no signs ...

  4. Lack of negative effects on Syrian hamsters and Mongolian gerbils housed in the same secondary enclosure.

    Science.gov (United States)

    Pritchett-Corning, Kathleen R; Gaskill, Brianna N

    2015-05-01

    In cases where different species might be housed in the same room or secondary enclosure, the Guide for the Care and Use of Laboratory Animals recommends that the animals should be behaviorally compatible and have the same health status. Syrian hamsters and Mongolian gerbils, both desert-dwelling rodents, appear to be reasonable candidates for such a combination. This study was undertaken to evaluate whether housing hamsters and gerbils in the same secondary enclosure is an acceptable practice. Weanling and breeding-age hamsters and gerbils were housed in open-topped cages in an isolator for 5 mo; the isolator also contained with nude and haired mice, which acted as sentinels. Cages housing hamsters and gerbils were rotated between species, and dirty bedding was exchanged between species in an effort to transmit microorganisms. In addition, sentinel mice housed in the isolator were supplied with dirty bedding from both hamsters and gerbils. Neither species showed clinical signs of illness, the health status of neither the hamsters nor the gerbils changed significantly, and the sentinel mice acquired only 2 infectious organisms, a Helicobacter species and Staphylococcus aureus. Both hamsters and gerbils bred successfully when housed together in the same isolator, and no infanticide or mortality was seen. Breeding performance did not differ between isolator breeding and barrier breeding. This study supports the housing of hamsters and gerbils in the same secondary enclosure. PMID:26045450

  5. CARBENDAZIM (MBC) DISRUPTS OOCYTE SPINDLE FUNCTION AND INDUCES ANEUPLOIDY IN HAMSTERS EXPOSED DURING FERTILIZATION (MEIOSIS II)

    Science.gov (United States)

    Peri-fertilization exposure to Carbendazim (MBC; a microtubule poison) induces infertility and early pregnancy loss (EPL) in hamsters. resently, both in vivo and in vitro techniques were employed to characterize the effects of MBC on cellular aspects of fertilization in hamsters....

  6. The Chemistry of Cold: Mechanisms of Torpor Regulation in the Siberian Hamster.

    Science.gov (United States)

    Cubuk, Ceyda; Bank, Jonathan H H; Herwig, Annika

    2016-01-01

    Siberian hamsters use spontaneous daily torpor, a state of hypometabolism and hypothermia, to save energy during winter. Multiple neuroendocrine signals set the scene for spontaneous torpor to occur, and several brain areas have been identified as potential sites for torpor regulation. Here, we summarize the known mechanisms of a fascinating physiological state in the Siberian hamster.

  7. Diet affects resting, but not basal metabolic rate of normothermic Siberian hamsters acclimated to winter.

    Science.gov (United States)

    Gutowski, Jakub P; Wojciechowski, Michał S; Jefimow, Małgorzata

    2011-12-01

    We examined the effect of different dietary supplements on seasonal changes in body mass (m(b)), metabolic rate (MR) and nonshivering thermogenesis (NST) capacity in normothermic Siberian hamsters housed under semi-natural conditions. Once a week standard hamster food was supplemented with either sunflower and flax seeds, rich in polyunsaturated fatty acids (FA), or mealworms, rich in saturated and monounsaturated FA. We found that neither of these dietary supplements affected the hamsters' normal winter decrease in m(b) and fat content nor their basal MR or NST capacity. NST capacity of summer-acclimated hamsters was lower than that of winter-acclimated ones. The composition of total body fat reflected the fat composition of the dietary supplements. Resting MR below the lower critical temperature of the hamsters, and their total serum cholesterol concentration were lower in hamsters fed a diet supplemented with mealworms than in hamsters fed a diet supplemented with seeds. These results indicate that in mealworm-fed hamsters energy expenditure in the cold is lower than in animals eating a seed-supplemented diet, and that the degree of FA unsaturation of diet affects energetics of heterotherms, not only during torpor, but also during normothermy.

  8. Adenoviral delivery of pan-caspase inhibitor p35 enhances bystander killing by P450 gene-directed enzyme prodrug therapy using cyclophosphamide+

    International Nuclear Information System (INIS)

    Cytochrome P450-based suicide gene therapy for cancer using prodrugs such as cyclophosphamide (CPA) increases anti-tumor activity, both directly and via a bystander killing mechanism. Bystander cell killing is essential for the clinical success of this treatment strategy, given the difficulty of achieving 100% efficient gene delivery in vivo using current technologies. Previous studies have shown that the pan-caspase inhibitor p35 significantly increases CPA-induced bystander killing by tumor cells that stably express P450 enzyme CYP2B6 (Schwartz et al, (2002) Cancer Res. 62: 6928-37). To further develop this approach, we constructed and characterized a replication-defective adenovirus, Adeno-2B6/p35, which expresses p35 in combination with CYP2B6 and its electron transfer partner, P450 reductase. The expression of p35 in Adeno-2B6/p35-infected tumor cells inhibited caspase activation, delaying the death of the CYP2B6 'factory' cells that produce active CPA metabolites, and increased bystander tumor cell killing compared to that achieved in the absence of p35. Tumor cells infected with Adeno-2B6/p35 were readily killed by cisplatin and doxorubicin, indicating that p35 expression is not associated with acquisition of general drug resistance. Finally, p35 did not inhibit viral release when the replication-competent adenovirus ONYX-017 was used as a helper virus to facilitate co-replication and spread of Adeno-2B6/p35 and further increase CPA-induced bystander cell killing. The introduction of p35 into gene therapeutic regimens constitutes an effective approach to increase bystander killing by cytochrome P450 gene therapy. This strategy may also be used to enhance other bystander cytotoxic therapies, including those involving the production of tumor cell toxic protein products

  9. Contribution of nitric oxide radicals in bystander and adaptive responses induced by heavy ion-beams

    International Nuclear Information System (INIS)

    The purpose of this study was to investigate whether radioadaptive responses were induced after irradiation with accelerated ion beams through nitric oxide-mediated bystander response in cultured cells in vitro and in some organs of mice in vivo. Human non-small cell lung carcinoma cells transfected with wild-type p53 (H1299/wtp53 cells) were used. The cells were irradiated with accelerated carbon ion beams (290 MeV/u, 31 keV/μm or 135 MeV/u, 31 keV/μm). Then, the cells were allowed forming colonies. ICR male mice (Jcl: ICR) were used. The mice were irradiated on 2 days with accelerated carbon ion beams (290 MeV/u, 13 keV/μm or 135 MeV/u, 25 keV/μm) or argon ion beams (500 MeV/u, 90 keV/μm). The small intestine and testis were excised 2 days after the last irradiation. These excised tissues were fixed, embedded in paraffin and made of thin-sections on slide glasses. Then the TUNEL- and activated caspase-3-positive cells in the thin-sections of tissues were detected by the immunohistochemical method. A significant elevated surviving fractions of cells was observed when the cells were challengingly irradiated after the priming irradiation with accelerate carbon ion beams. This enhancement was partially suppressed by Nitric oxide (NO) radical scavenger, carboxy-PTIO (c-PTIO). The bystander-induced apoptotic and activated caspase-3-positive cells were obviously observed in the unirradiated small intestine and testis when mice were irradiated with carbon or argon ion beams across the upper body. In addition, a significant reduction of apoptotic cells in the intestine and testis, when mice were challengingly irradiated after the priming irradiation with accelerate carbon or argon ion beams. These observations were partially suppressed by c-PTIO into the peritoneal cavity. Furthermore, it is suggested that the apoptosis may be induced in the tissue stem cells of small intestine and testis. (author)

  10. Melatonin attenuates photic disruption of circadian rhythms in Siberian hamsters.

    Science.gov (United States)

    Ruby, N F; Kang, T; Heller, H C

    1997-10-01

    Body temperature (Tb) was recorded via a biotelemetry system from 28 adult male Siberian hamsters maintained in a light-dark (LD) cycle of 16 h light/day for several months. After Tb was recorded for 3 wk, the LD cycle was phase delayed by extending the light phase by 5 h for 1 day; animals remained on a 16:8 LD cycle for the remainder of the experiment. Hamsters were injected daily with melatonin or vehicle solution for several weeks, beginning either 2 mo after (experiment 1) or on the day of (experiment 2) the phase shift; injections occurred within 30 min of dark onset. In experiment 1, 75% of animals free ran with circadian periods >24 h, beginning on the day of the phase shift, and never reentrained to the LD cycle; no hamsters unambiguously entrained to daily injections. In contrast, 78% of animals in experiment 2 entrained to melatonin injections, and 71% of those animals subsequently reentrained to the photocycle when the injection regimen ended. No vehicle-treated animals entrained to the injection schedule. Melatonin had no effect on daily mean Tb and Tb rhythm amplitude in either experiment; however, melatonin doubled the duration of a hyperthermic response that occurred after each injection. Thus melatonin can prevent loss of entrainment induced by a phase shift of the LD cycle but cannot restore entrainment to free-running animals. Failure to reentrain in the presence of two appropriately coordinated entraining agents also suggests that a phase shift of the photocycle can diminish the sensitivity of the circadian system to both photic and nonphotic input.

  11. Photoperiodic regulation of FGF21 production in the Siberian hamster.

    Science.gov (United States)

    Samms, Ricardo J; Fowler, Maxine J; Cooper, Scott; Emmerson, Paul; Coskun, Tamer; Adams, Andrew C; Kharitonenkov, Alexei; Tsintzas, Kostas; Ebling, Francis J P

    2014-06-01

    This article is part of a Special Issue "Energy Balance". FGF21 is an endocrine member of the fibroblast growth factor superfamily that has been shown to play an important role in the physiological response to nutrient deprivation. Food restriction enhances hepatic FGF21 production, which serves to engage an integrated response to energy deficit. Specifically, elevated FGF21 levels lead to reduced gluconeogenesis and increased hepatic ketogenesis. However, circulating FGF21 concentrations also paradoxically rise in states of metabolic dysfunction such as obesity. Furthermore, multiple peripheral tissues also produce FGF21 in addition to the liver, raising questions as to its endocrine and paracrine roles in the control of energy metabolism. The objectives of this study were to measure plasma FGF21 concentrations in the Siberian hamster, a rodent which undergoes a seasonal cycle of fattening and body weight gain in the long days (LD) of summer, followed by reduction of appetite and fat catabolism in the short days (SD) of winter. Groups of adult male hamsters were raised in long days, and then exposed to SD for up to 12 weeks. Chronic exposure of LD animals to SD led to a significant increase in circulating FGF21 concentrations. This elevation of circulating FGF21 was preceded by an increase in liver FGF21 protein production evident as early as 4 weeks of exposure to SD. FGF21 protein abundance was also increased significantly in interscapular brown adipose tissue, with a positive correlation between plasma levels of FGF21 and BAT protein abundance throughout the experimental period. Epididymal white adipose tissue and skeletal muscle (gastrocnemius) also produced FGF21, but levels did not change in response to a change in photoperiod. In summary, a natural programmed state of fat catabolism was associated with increased FGF21 production in the liver and BAT, consistent with the view that FGF21 has a role in adapting hamsters to the hypophagic winter state.

  12. Teens’ Self-Efficacy to Deal with Dating Violence as Victim, Perpetrator or Bystander

    Science.gov (United States)

    Van Camp, Tinneke; Hébert, Martine; Guidi, Elisa; Lavoie, Francine; Blais, Martin

    2015-01-01

    Multiple studies have demonstrated that adolescent dating violence is highly prevalent and associated with internalizing and externalizing problems. A number of prevention initiatives are being implemented in North-American high schools. Such initiatives do not only aim to raise awareness among potential victims and offenders but also among peer bystanders. Since teenagers mainly reach out to their peers when experiencing adversity, it is important to address adolescents’ efficiency to deal with witnessing dating violence or with friends disclosing dating abuse, in addition to increasing ability to deal with experienced dating violence victimization or perpetration. The aim of this study is to explore adolescents’ self-efficacy to deal with dating violence victimization and perpetration in their relationships and those of their peers. A paper-and-pencil questionnaire was completed by 259 14–18 years olds in Quebec, Canada. The data allows building insight into adolescents’ confidence to reach out for help or to help others in a situation of dating violence victimization and perpetration. We also considered the impact of gender and dating victimization history. Results suggest that dating violence prevention can build on teens’ self-efficacy to deal with dating violence and offer them tools to do so efficiently. PMID:26807554

  13. Presence of viral nucleic acids in the middle ear: acute otitis media pathogen or bystander?

    Science.gov (United States)

    Chonmaitree, Tasnee; Ruohola, Aino; Hendley, J Owen

    2012-04-01

    Viruses play an important role in acute otitis media (AOM) pathogenesis, and live viruses may cause AOM in the absence of pathogenic bacteria. Detection of AOM pathogens generally relies on bacterial culture of middle ear fluid. When viral culture is used and live viruses are detected in the middle ear fluid of children with AOM, the viruses are generally accepted as AOM pathogens. Because viral culture is not sensitive and does not detect the comprehensive spectrum of respiratory viruses, polymerase chain reaction assays are commonly used to detect viral nucleic acids in the middle ear fluid. Although polymerase chain reaction assays have greatly increased the viral detection rate, new questions arise on the significance of viral nucleic acids detected in the middle ear because nucleic acids of multiple viruses are detected simultaneously, and nucleic acids of specific viruses are detected repeatedly and in a high proportion of asymptomatic children. This article first reviews the role of live viruses in AOM and presents the point-counterpoint arguments on whether viral nucleic acids in the middle ear represent an AOM pathogen or a bystander status. Although there is evidence to support both directions, helpful information for interpretation of the data and future research direction is outlined.

  14. Cancer Stem Cells Protect Non-Stem Cells From Anoikis: Bystander Effects.

    Science.gov (United States)

    Kim, Seog-Young; Hong, Se-Hoon; Basse, Per H; Wu, Chuanyue; Bartlett, David L; Kwon, Yong Tae; Lee, Yong J

    2016-10-01

    Cancer stem cells (CSCs) are capable of initiation and metastasis of tumors. Therefore, understanding the biology of CSCs and the interaction between CSCs and their counterpart non-stem cells is crucial for developing a novel cancer therapy. We used CSC-like and non-stem breast cancer MDA-MB-231 and MDA-MB-453 cells to investigate mammosphere formation. We investigated the role of the epithelial cadherin (E-cadherin)-extracellular signal-regulated kinase (Erk) axis in anoikis. Data from E-cadherin small hairpin RNA assay and mitogen-activated protein kinase kinase (MEK) inhibitor study show that activation of Erk, but not modulation of E-cadherin level, may play an important role in anoikis resistance. Next, the two cell subtypes were mixed and the interaction between them during mammosphere culture and xenograft tumor formation was investigated. Unlike CSC-like cells, increased secretion of interleukin-6 (IL-6) and growth-related oncogene (Gro) chemokines was detected during mammosphere culture in non-stem cells. Similar results were observed in mixed cells. Interestingly, CSC-like cells protected non-stem cells from anoikis and promoted tumor growth. Our results suggest bystander effects between CSC-like cells and non-stem cells. J. Cell. Biochem. 117: 2289-2301, 2016. © 2016 Wiley Periodicals, Inc. PMID:26918647

  15. Bystander activation of CD8+ T lymphocytes during experimental mycobacterial infection.

    Science.gov (United States)

    Gilbertson, Brad; Germano, Susie; Steele, Pauline; Turner, Steven; Fazekas de St Groth, Barbara; Cheers, Christina

    2004-12-01

    Infection of C57BL/6 mice with Mycobacterium avium leads to the activation of both CD4+ and CD8+ gamma interferon (IFN-gamma)-producing T cells, although the CD8+ cells play no role in protection against infection. Using transfer of different lines of transgenic T cells with T-cell receptors (TCRs) which recognize irrelevant antigens, we show here that transferred CD8+ T cells from two of the three lines were activated to the same degree as the host cells, suggesting that the majority of the IFN-gamma-producing CD8+ T cells of the host represented bystander activation. The third line, specific for the male HY antigen, showed no activation. Activation required the participation of the CD28 coreceptor on T cells and was unaffected by the removal of CD44(hi) (memory phenotype) T cells. The transferred CD8+ T cells proliferated in vivo, although this was not essential for IFN-gamma production. Taken together, these data are highly reminiscent of homeostatic proliferation of TCR transgenic T cells upon transfer to lymphopenic hosts, and suggest low-affinity stimulation through the TCR, possibly by self peptides. The findings are discussed in relation to homeostatic proliferation and their significance in the possible induction of autoimmune disease.

  16. Virtual bystanders in a language lesson: examining the effect of social evaluation, vicarious experience, cognitive consistency and praising on students' beliefs, self-efficacy and anxiety in a virtual reality environment

    NARCIS (Netherlands)

    Qu, C.; Ling, Y.; Heynderickx, I.; Brinkman, W.-P.

    2015-01-01

    Bystanders in a real world's social setting have the ability to influence people’s beliefs and behavior. This study examines whether this effect can be recreated in a virtual environment, by exposing people to virtual bystanders in a classroom setting. Participants (n = 26) first witnessed virtual s

  17. Sex differences in Siberian hamster ultradian locomotor rhythms.

    Science.gov (United States)

    Prendergast, Brian J; Stevenson, Tyler J; Zucker, Irving

    2013-02-17

    Sex differences in ultradian activity rhythms (URs) and circadian rhythms (CRs) were assessed in Siberian hamsters kept in long day (LD) or short day (SD) photoperiods for 40 weeks. For both sexes URs of locomotor activity were more prevalent, greater in amplitude and more robust in SDs. The UR period was longer in females than males in both day lengths. The reproductive system underwent regression and body mass declined during the initial 10 weeks of SD treatment, and in both sexes these traits spontaneously reverted to the LD phenotype at or before 40 weeks in SD, reflecting the development of neuroendocrine refractoriness to SD patterns of melatonin secretion. Hamsters of both sexes, however, continued to display SD-like URs at the 40 weeks time point. CRs were less prevalent and the waveform less robust and lower in amplitude in SDs than LDs; the SD circadian waveform also did not revert to the long-day phenotype after 40 weeks of SD treatment. Short day lengths enhanced ultradian and diminished circadian rhythms in both sexes. Day length controls several UR characteristics via gonadal steroid and melatonin-independent mechanisms. Sex differences in ultradian timing may contribute to sex diphenisms in rhythms of sleep, food intake and exercise.

  18. Constant darkness restores entrainment to phase-delayed Siberian hamsters.

    Science.gov (United States)

    Ruby, Norman F; Joshi, Nirav; Heller, H Craig

    2002-12-01

    Over 90% of Siberian hamsters (Phodopus sungorus) fail to reentrain to a 5-h phase delay of a 16:8-h photocycle. Because constant darkness (DD) restores rhythms disrupted by constant light, we tested whether DD could also restore entrainment. DD began 0, 5, or 14 days after a 5-h phase delay, and the light-dark cycle was reinstated 14 days later. All hamsters exposed to DD on day 0 reentrained, whereas 42% reentrained irrespective of whether DD began 5 or 14 days later. For these latter two groups, tau (tau) and alpha (alpha) in DD predicted reentrainment; animals that reentrained had a mean tau and alpha of 24.1 and 8.9 h, respectively, whereas those that failed to reentrain maintained a mean tau and alpha of 25.0 and of 7.1 h, respectively. Restoration of entrainment by DD is somewhat paradoxical because it suggests that reentrainment to the photocycle was prevented by continued exposure to that same photocycle. The dichotomy of circadian responses to DD suggests "entrainment" phenotypes that are similar to those of photoperiodic responders and nonresponders.

  19. Rift Valley fever virus infection in golden Syrian hamsters.

    Directory of Open Access Journals (Sweden)

    Dionna Scharton

    Full Text Available Rift Valley fever virus (RVFV is a formidable pathogen that causes severe disease and abortion in a variety of livestock species and a range of disease in humans that includes hemorrhagic fever, fulminant hepatitis, encephalitis and blindness. The natural transmission cycle involves mosquito vectors, but exposure can also occur through contact with infected fluids and tissues. The lack of approved antiviral therapies and vaccines for human use underlies the importance of small animal models for proof-of-concept efficacy studies. Several mouse and rat models of RVFV infection have been well characterized and provide useful systems for the study of certain aspects of pathogenesis, as well as antiviral drug and vaccine development. However, certain host-directed therapeutics may not act on mouse or rat pathways. Here, we describe the natural history of disease in golden Syrian hamsters challenged subcutaneously with the pathogenic ZH501 strain of RVFV. Peracute disease resulted in rapid lethality within 2 to 3 days of RVFV challenge. High titer viremia and substantial viral loads were observed in most tissues examined; however, histopathology and immunostaining for RVFV antigen were largely restricted to the liver. Acute hepatocellular necrosis associated with a strong presence of viral antigen in the hepatocytes indicates that fulminant hepatitis is the likely cause of mortality. Further studies to assess the susceptibility and disease progression following respiratory route exposure are warranted. The use of the hamsters to model RVFV infection is suitable for early stage antiviral drug and vaccine development studies.

  20. Nontoxigenic Clostridium difficile Protects Hamsters against Challenge with Historic and Epidemic Strains of Toxigenic BI/NAP1/027 C. difficile

    OpenAIRE

    Nagaro, Kristin J.; Phillips, S. Tyler; Cheknis, Adam K.; Sambol, Susan P.; Zukowski, Walter E.; Johnson, Stuart; Gerding, Dale N.

    2013-01-01

    Nontoxigenic Clostridium difficile (NTCD) has been shown to prevent fatal C. difficile infection in the hamster model when hamsters are challenged with standard toxigenic C. difficile strains. The purpose of this study was to determine if NTCD can prevent C. difficile infection in the hamster model when hamsters are challenged with restriction endonuclease analysis group BI C. difficile strains. Groups of 10 hamsters were given oral clindamycin, followed on day 2 by 106 CFU of spores of NTCD ...

  1. Pineal-independent regulation of photo-nonresponsiveness in the Siberian hamster (Phodopus sungorus).

    Science.gov (United States)

    Prendergast, B J; Freeman, D A

    1999-02-01

    The pineal hormone melatonin influences circadian rhythms and also mediates reproductive responses to photoperiod. The authors tested whether pinealectomy influences circadian oscillators responsible for induction of nonresponsiveness to short day lengths by preventing normal short-day patterns of circadian entrainment. Adult male Siberian hamsters were pinealectomized or sham operated, maintained in either 18 h light per day (18L) or 15L for 10 weeks, and then tested for responsiveness to 10L. Because pinealectomized hamsters do not show gonadal regression in short day lengths, responsiveness was assessed by measuring phase angle of entrainment and the length of the nightly activity period following transfer to 10L. The incidence of nonresponsiveness was significantly higher in 18L hamsters than in 15L hamsters but was unaffected by pineal status. Fully 88% of 18L hamsters failed to entrain to 10L in the normal short-day manner; the duration of nightly activity remained compressed, and the phase angle of entrainment was large and negative relative to lights off. The 15L hamsters entrained normally to 10L. Exposure to constant light after 10L treatment was equally effective in inducing arrhythmicity in pinealectomized and intact hamsters. Changes in the period of morning and evening circadian oscillators subsequent to 18L treatment did not predict circadian responsiveness to short photoperiod. Long-day induction of photo-nonresponsiveness, which prevents winter responses to short day lengths, occurs independently of pineal melatonin feedback on the circadian system.

  2. Bioavailability and disposition of 3H-solanine in rat and hamster.

    Science.gov (United States)

    Groen, K; Pereboom-de Fauw, D P; Besamusca, P; Beekhof, P K; Speijers, G J; Derks, H J

    1993-09-01

    1. The toxicokinetics of [3H]-alpha-solanine after oral (p.o.) and intravenous (i.v.) administration in rat and hamster were studied, in order to decide which is the most appropriate model in risk assessment studies. The i.v. dose was 54 micrograms/kg; the oral dose was 170 micrograms/kg. 2. After i.v. administration, the toxicokinetics of total radioactivity in blood were comparable in rat and hamster. However, the clearance of total radioactivity from plasma was more effective in rat than in hamster. The half-lives of distribution and of the terminal phase of unchanged alpha-solanine were not different between rat and hamster, whereas the systemic and metabolic clearance were, respectively, about 1.6 and 2.7 times higher in rat than in hamster. The clearance of unchanged alpha-solanine is more effective than of total radioactivity. 3. After p.o. administration in rat and hamster, the mean bioavailability of total radioactivity is about 29 and 57%, respectively. The bioavailability of unchanged alpha-solanine is only 1.6 and 3.2%, respectively, when compared with i.v. administration. 4. T1/2el of alpha-solanine after p.o. administration was in rats a factor of four and in hamsters a factor of two shorter than after i.v. administration. A strong retention of radioactivity was seen in the hamsters after p.o. administration; only 40% of the dose was excreted within 7 days versus 90% in rat. 5. Based on these and toxicological data from literature, it was decided that the hamster is a more appropriate model in (sub)-chronic toxicity studies with alpha-solanine than the rat.

  3. Association of national initiatives to improve cardiac arrest management with rates of bystander intervention and patient survival after out-of-hospital cardiac arrest

    DEFF Research Database (Denmark)

    Wissenberg, Mads; Lippert, Freddy K.; Folke, Fredrik;

    2013-01-01

    resuscitation was attempted were identified between 2001 and 2010 in the nationwide Danish Cardiac Arrest Registry. Of 29 111 patients with cardiac arrest, we excluded those with presumed noncardiac cause of arrest (n = 7390) and those with cardiac arrests witnessed by emergency medical services personnel (n......IMPORTANCE Out-of-hospital cardiac arrest is a major health problem associated with poor outcomes. Early recognition and intervention are critical for patient survival. Bystander cardiopulmonary resuscitation (CPR) is one factor among many associated with improved survival. OBJECTIVE To examine...... temporal changes in bystander resuscitation attempts and survival during a 10-year period in which several national initiatives were taken to increase rates of bystander resuscitation and improve advanced care. DESIGN, SETTING, AND PARTICIPANTS Patients with out-of-hospital cardiac arrest for which...

  4. Determination of elements in blood of golden hamster by NAA; Determinacao de elementos em sangue de hamster dourado usando AAN

    Energy Technology Data Exchange (ETDEWEB)

    Aguiar, Rodrigo Oliveira de

    2009-07-01

    In the present study Neutron Activation Analysis technique has been used to determine, simultaneously, some element concentrations of clinical relevance in whole blood samples of golden hamster. The normal range for Br, Ca, Cl K, Mg, Na and S considering 2 {sigma} (Two Standard deviations) was 0.011 0.047 gL{sup -1} (Br); 0.11 0.35 gL{sup -1} (Ca); 2.11 3.75 gL{sup -1} (Cl); 1.35 2.79 gL{sup -1} (K), 0.026 0.090 gL{sup -1} (Mg), 1.03 2.51 gL{sup -1} (Na) e 0.97 2.01 gL{sup -1} (S). The knowledge of these limits became possible to perform clinical investigation in this animal model using whole blood. The comparison with the results from human being whole blood estimation (Hamster and human) became possible to check the similarities or physiologic differences, an important data for animal experimentation. (author)

  5. Virtual bystanders in a language lesson: examining the effect of social evaluation, vicarious experience, cognitive consistency and praising on students' beliefs, self-efficacy and anxiety in a virtual reality environment.

    Science.gov (United States)

    Qu, Chao; Ling, Yun; Heynderickx, Ingrid; Brinkman, Willem-Paul

    2015-01-01

    Bystanders in a real world's social setting have the ability to influence people's beliefs and behavior. This study examines whether this effect can be recreated in a virtual environment, by exposing people to virtual bystanders in a classroom setting. Participants (n = 26) first witnessed virtual students answering questions from an English teacher, after which they were also asked to answer questions from the teacher as part of a simulated training for spoken English. During the experiment the attitudes of the other virtual students in the classroom was manipulated; they could whisper either positive or negative remarks to each other when a virtual student was talking or when a participant was talking. The results show that the expressed attitude of virtual bystanders towards the participants affected their self-efficacy, and their avoidance behavior. Furthermore, the experience of witnessing bystanders commenting negatively on the performance of other students raised the participants' heart rate when it was their turn to speak. Two-way interaction effects were also found on self-reported anxiety and self-efficacy. After witnessing bystanders' positive attitude towards peer students, participants' self-efficacy when answering questions received a boost when bystanders were also positive towards them, and a blow when bystanders reversed their attitude by being negative towards them. Still, inconsistency, instead of consistency, between the bystanders' attitudes towards virtual peers and the participants was not found to result in a larger change in the participants' beliefs. Finally the results also reveal that virtual flattering or destructive criticizing affected the participants' beliefs not only about the virtual bystanders, but also about the neutral teacher. Together these findings show that virtual bystanders in a classroom can affect people's beliefs, anxiety and behavior. PMID:25884211

  6. Virtual bystanders in a language lesson: examining the effect of social evaluation, vicarious experience, cognitive consistency and praising on students' beliefs, self-efficacy and anxiety in a virtual reality environment.

    Directory of Open Access Journals (Sweden)

    Chao Qu

    Full Text Available Bystanders in a real world's social setting have the ability to influence people's beliefs and behavior. This study examines whether this effect can be recreated in a virtual environment, by exposing people to virtual bystanders in a classroom setting. Participants (n = 26 first witnessed virtual students answering questions from an English teacher, after which they were also asked to answer questions from the teacher as part of a simulated training for spoken English. During the experiment the attitudes of the other virtual students in the classroom was manipulated; they could whisper either positive or negative remarks to each other when a virtual student was talking or when a participant was talking. The results show that the expressed attitude of virtual bystanders towards the participants affected their self-efficacy, and their avoidance behavior. Furthermore, the experience of witnessing bystanders commenting negatively on the performance of other students raised the participants' heart rate when it was their turn to speak. Two-way interaction effects were also found on self-reported anxiety and self-efficacy. After witnessing bystanders' positive attitude towards peer students, participants' self-efficacy when answering questions received a boost when bystanders were also positive towards them, and a blow when bystanders reversed their attitude by being negative towards them. Still, inconsistency, instead of consistency, between the bystanders' attitudes towards virtual peers and the participants was not found to result in a larger change in the participants' beliefs. Finally the results also reveal that virtual flattering or destructive criticizing affected the participants' beliefs not only about the virtual bystanders, but also about the neutral teacher. Together these findings show that virtual bystanders in a classroom can affect people's beliefs, anxiety and behavior.

  7. A comparative study of the pulmonary effects of NO2 in the rat and hamster.

    OpenAIRE

    Foster, J R; Cottrell, R C; Herod, I. A.; Atkinson, H. A.; Miller, K

    1985-01-01

    A study of the response of rat and hamster to nitrogen dioxide (NO2) under identical conditions has been undertaken. Exposure to 20 parts/IO6 NO2 for 24 h produced a mild cytotoxic effect on the terminal bronchiole and proximal alveoli in the rat, whereas the hamster developed a moderate to severe bronchiolitis and alveolitis. Electron microscopic examination of tissue sections showed accumulation of surfactant in lamellar bodies of the alveolar type II cell in the rat but not in the hamster,...

  8. In vitro metabolism of cannabinol in rat, mouse, rabbit, guinea pig, hamster, gerbil and cat.

    Science.gov (United States)

    Brown, N K; Harvey, D J

    1990-01-01

    Metabolism of cannabinol (CBN) was studied in hepatic microsomal incubates from mouse, rat, rabbit, guinea pig, cat, hamster and gerbil. Metabolites were extracted with ethyl acetate, concentrated by chromatography on Sephadex LH-20 and identified by GC/MS as TMS derivatives. Six monohydroxy metabolites were identified. These had hydroxy groups at C-11 and at all positions of the pentyl side-chain. Metabolism varied considerably between the species. 11-Hydroxylation was the most prominent route in the majority of species, but in the hamster and cat the major metabolic pathway was 4'-hydroxylation. Metabolites hydroxylated in the pentyl chain were generally more abundant in guinea pig, hamster and cat. PMID:2253656

  9. SirT1 knockdown potentiates radiation-induced bystander effect through promoting c-Myc activity and thus facilitating ROS accumulation

    Energy Technology Data Exchange (ETDEWEB)

    Xie, Yuexia [Institute of Radiation Medicine, Fudan University, Shanghai (China); Central Laboratory, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai (China); Tu, Wenzhi; Zhang, Jianghong; He, Mingyuan; Ye, Shuang; Dong, Chen [Institute of Radiation Medicine, Fudan University, Shanghai (China); Shao, Chunlin, E-mail: clshao@shmu.edu.cn [Institute of Radiation Medicine, Fudan University, Shanghai (China)

    2015-02-15

    Highlights: • γ-Irradiation induced bystander effects between hepatoma cells and hepatocyte cells. • SirT1 played a protective role in regulating this bystander effect. • SirT1 contributed to the protective effects via elimination the accumulation of ROS. • The activity of c-Myc is critical for maintaining the protective role of SirT1. - Abstract: Radiation-induced bystander effect (RIBE) has important implications for secondary cancer risk assessment during cancer radiotherapy, but the bystander signaling processes, especially under hypoxic condition, are still largely unclear. The present study found that micronuclei (MN) formation could be induced in the non-irradiated HL-7702 hepatocyte cells after being treated with the conditioned medium from irradiated hepatoma HepG2 and SK-Hep-1 cells under either normoxia or hypoxia. This bystander response was dramatically diminished or enhanced when the SirT1 gene of irradiated hepatoma cells was overexpressed or knocked down, respectively, especially under hypoxia. Meanwhile, SirT1 knockdown promoted transcriptional activity for c-Myc and facilitated ROS accumulation. But both of the increased bystander responses and ROS generation due to SirT1-knockdown were almost completely suppressed by c-Myc interference. Moreover, ROS scavenger effectively abolished the RIBE triggered by irradiated hepatoma cells even with SirT1 depletion. These findings provide new insights that SirT1 has a profound role in regulating RIBE where a c-Myc-dependent release of ROS may be involved.

  10. Chinese Cooking.

    Science.gov (United States)

    Kane, Tony

    This unit, intended for secondary level students, is a general introduction to Chinese cooking. It is meant to inform students about the origins of Chinese cooking styles in their various regional manifestations, and it can be used to discuss how and why different cultures develop different styles of cooking. The first part of the unit, adapted…

  11. Cytosine Deaminase/5-Fluorocytosine Exposure Induces Bystander and Radiosensitization Effects in Hypoxic Glioblastoma Cells in vitro

    International Nuclear Information System (INIS)

    Purpose: Treatment of glioblastoma (GBM) is limited by therapeutic ratio; therefore, successful therapy must be specifically cytotoxic to cancer cells. Hypoxic cells are ubiquitous in GBM, and resistant to radiation and chemotherapy, and, thus, are logical targets for gene therapy. In this study, we investigated whether cytosine deaminase (CD)/5-fluorocytosine (5-FC) enzyme/prodrug treatment induced a bystander effect (BE) and/or radiosensitization in hypoxic GBM cells. Methods and Materials: We stably transfected cells with a gene construct consisting of the SV40 minimal promoter, nine copies of a hypoxia-responsive element, and the yeast CD gene. During hypoxia, a hypoxia-responsive element regulates expression of the CD gene and facilitates the conversion of 5-FC to 5-fluorouracil, a highly toxic antimetabolite. We used colony-forming efficiency (CFE) and immunofluorescence assays to assess for BE in co-cultures of CD-expressing clone cells and parent, pNeo- or green fluorescent protein-stably transfected GBM cells. We also investigated the radiosensitivity of CD clone cells treated with 5-FC under hypoxic conditions, and we used flow cytometry to investigate treatment-induced cell cycle changes. Results: Both a large BE and radiosensitization occurred in GBM cells under hypoxic conditions. The magnitude of the BE depended on the number of transfected cells producing CD, the functionality of the CD, the administered concentration of 5-FC, and the sensitivity of cell type to 5-fluorouracil. Conclusion: Hypoxia-inducible CD/5-FC therapy in combination with radiation therapy shows both a pronounced BE and a radiosensitizing effect under hypoxic conditions

  12. The effects of cell phone conversations on the attention and memory of bystanders.

    Directory of Open Access Journals (Sweden)

    Veronica V Galván

    Full Text Available The pervasive use of cell phones impacts many people-both cell phone users and bystanders exposed to conversations. This study examined the effects of overhearing a one-sided (cell phone conversation versus a two-sided conversation on attention and memory. In our realistic design, participants were led to believe they were participating in a study examining the relationship between anagrams and reading comprehension. While the participant was completing an anagram task, the researcher left the room and participants overheard a scripted conversation, either two confederates talking with each other or one confederate talking on a cell phone. Upon the researcher's return, the participant took a recognition memory task with words from the conversation, and completed a questionnaire measuring the distracting nature of the conversation. Participants who overheard the one-sided conversation rated the conversation as significantly higher in distractibility than those who overheard the two-sided conversation. Also, participants in the one-sided condition scored higher on the recognition task. In particular they were more confident and accurate in their responses to words from the conversation than participants in the two-sided condition. However, participants' scores on the anagram task were not significantly different between conditions. As in real world situations, individual participants could pay varying amounts of attention to the conversation since they were not explicitly instructed to ignore it. Even though the conversation was irrelevant to the anagram task and contained less words and noise, one-sided conversations still impacted participants' self-reported distractibility and memory, thus showing people are more attentive to cell phone conversations than two-sided conversations. Cell phone conversations may be a common source of distraction causing negative consequences in workplace environments and other public places.

  13. Bystander effects of the ionizing radiation and his implications in radiotherapy and radioprotection

    International Nuclear Information System (INIS)

    According to the classical paradigm, biological effects of ionizing radiation are attributed to DNA damage induced in each irradiated cell. Demonstration of ionizing radiation-induced bystander effects (RIBE) has generated a deep change in current understanding of radiobiology. RIBE are radiation-induced effects produced in cells that have not been actually irradiated. Several technical advances, particularly the use of microbeams, allowed in vitro study of RIBE. There are two known ways by which irradiated cells can communicate with non-irradiated cells, namely: through gap junctions connecting the cytoplasms of adjacent cells, and through the secretion of soluble factors to the extracellular medium. These factors include several cytokines and reactive species of oxygen and nitrogen. In the affected cells, signalling pathways mostly involve activation of mitogen-activated protein kinases (MAPK), NF-kB transcription factor and of the enzymes cyclooxygenase 2, nitric oxide synthase 2 and NAD (P)H oxidase. RIBE induce point mutations and epigenetic changes. Effects on cellular signalling pathways can persist indefinitely and even be transmitted to the progeny of affected cells. Paradoxically, under certain conditions RIBE may be adaptive, which means that they turn affected cells more resistant to ionizing radiation. Adaptation demands protein synthesis. It enhances DNA repair mechanisms and resistance to oxidative stress. RIBE have also been demonstrated in vivo. Thus, they may have important implications for radiotherapy, both to improve therapeutic efficacy and to reduce the incidence of adverse effects. Furthermore, a better understanding of RIBE may have an influence on international radioprotection standards. (authors)

  14. Versatile microscale screening platform for improving recombinant protein productivity in Chinese hamster ovary cells

    DEFF Research Database (Denmark)

    Hansen, Henning Gram; Nilsson, Claes Nymand; Lund, Anne Mathilde;

    2015-01-01

    to reduce production costs significantly. The aim of this study was to establish a versatile target gene screening platform for improving productivity for primarily non-mAb glycoproteins with complete interchangeability of model proteins and target genes using transient expression. The platform consists...... of four techniques compatible with 96-well microplates: lipid-based transient transfection, cell cultivation in microplates, cell counting and antibody-independent product titer determination based on split-GFP complementation. We were able to demonstrate growth profiles and volumetric productivity of CHO...... cells in 96-half-deepwell microplates comparable with those obtained in shake flasks. In addition, we demonstrate that split-GFP complementation can be used to accurately measure relative titers of therapeutic glycoproteins. Using this platform, we were able to detect target gene-specific increase...

  15. Expression of recombinant rat Neurotrophin-3 in Chinese hamster ovary cells

    Institute of Scientific and Technical Information of China (English)

    季爱民; 舒斯云; 包新民; 邹恒琴; 张忠义; 李明

    1999-01-01

    The CHO cell line stably producing recombinant rat NT-3 was established. The insertion of rNT-3 cDNA into transferred cell gonome was analyzed with Southern blot. The expressed protein was identified by Dot ELISA (enzyme-linked immunosorbent assay) and Western blot. Western blot showed a clear specifie band of about 14 ku for NT-3. The mean level of rNT-3 in four NT-3eDNA/CHO cell lines was about 2 100 ng/10~6 cells/48 h determined by EIA. The conditioned-medium (CM) of NT-3cDNA/CHO cells could promote the fiber outgrowth of the dissociated dorsal root ganglion of 8-day-old chick embryos, which shows a dose-response relationship. A half-maximal concentration of the biological activity (EC50) of the recombinant protein was approximately 16.7 ng/mL. The MoAb 3W3 of NT-3 could neutralize the biological activity of the rNT-3.

  16. A theoretical estimate for nucleotide sugar demand towards Chinese Hamster Ovary cellular glycosylation

    Science.gov (United States)

    del Val, Ioscani Jimenez; Polizzi, Karen M.; Kontoravdi, Cleo

    2016-01-01

    Glycosylation greatly influences the safety and efficacy of many of the highest-selling recombinant therapeutic proteins (rTPs). In order to define optimal cell culture feeding strategies that control rTP glycosylation, it is necessary to know how nucleotide sugars (NSs) are consumed towards host cell and rTP glycosylation. Here, we present a theoretical framework that integrates the reported glycoproteome of CHO cells, the number of N-linked and O-GalNAc glycosylation sites on individual host cell proteins (HCPs), and the carbohydrate content of CHO glycosphingolipids to estimate the demand of NSs towards CHO cell glycosylation. We have identified the most abundant N-linked and O-GalNAc CHO glycoproteins, obtained the weighted frequency of N-linked and O-GalNAc glycosites across the CHO cell proteome, and have derived stoichiometric coefficients for NS consumption towards CHO cell glycosylation. By combining the obtained stoichiometric coefficients with previously reported data for specific growth and productivity of CHO cells, we observe that the demand of NSs towards glycosylation is significant and, thus, is required to better understand the burden of glycosylation on cellular metabolism. The estimated demand of NSs towards CHO cell glycosylation can be used to rationally design feeding strategies that ensure optimal and consistent rTP glycosylation. PMID:27345611

  17. Generation of a Chinese Hamster Ovary Cell Line Producing Recombinant Human Glucocerebrosidase

    Directory of Open Access Journals (Sweden)

    Juliana Branco Novo

    2012-01-01

    Full Text Available Impaired activity of the lysosomal enzyme glucocerebrosidase (GCR results in the inherited metabolic disorder known as Gaucher disease. Current treatment consists of enzyme replacement therapy by administration of exogenous GCR. Although effective, it is exceptionally expensive, and patients worldwide have a limited access to this medicine. In Brazil, the public healthcare system provides the drug free of charge for all Gaucher’s patients, which reaches the order of $ 84 million per year. However, the production of GCR by public institutions in Brazil would reduce significantly the therapy costs. Here, we describe a robust protocol for the generation of a cell line producing recombinant human GCR. The protein was expressed in CHO-DXB11 (dhfr− cells after stable transfection and gene amplification with methotrexate. As expected, glycosylated GCR was detected by immunoblotting assay both as cell-associated (~64 and 59 kDa and secreted (63–69 kDa form. Analysis of subclones allowed the selection of stable CHO cells producing a secreted functional enzyme, with a calculated productivity of 5.14 pg/cell/day for the highest producer. Although being laborious, traditional methods of screening high-producing recombinant cells may represent a valuable alternative to generate expensive biopharmaceuticals in countries with limited resources.

  18. Glycoengineering of Chinese hamster ovary cells for enhanced erythropoietin N-glycan branching and sialylation

    DEFF Research Database (Denmark)

    Yin, Bojiao; Gao, Yuan; Chung, Cheng-yu;

    2015-01-01

    increased by 26%. The increase in sialic acid content was further verified by detailed profiling of the N-glycan structures using mass spectra (MS) analysis. In order to enhance antennarity/branching, UDP-N-acetylglucosamine: α-1,3-D-mannoside β1,4-N-acetylglucosaminyltransferase (GnTIV/Mgat4) and UDP...

  19. Kisspeptin and the seasonal control of reproduction in hamsters

    DEFF Research Database (Denmark)

    Simonneaux, Valérie; Ansel, Laura; Revel, Florent G;

    2008-01-01

    Reproduction is a complex and energy demanding function. When internal and external conditions might impair reproductive success (negative energy balance, stress, harsh season) reproductive activity has to be repressed. Recent evidence suggests that these inhibitory mechanisms operate on Kiss1......-expressing neurons, which were recently shown to be implicated in the regulation of GnRH release. Hamsters are seasonal rodents which are sexually active in long photoperiod and quiescent in short photoperiod. The photoperiodic information is transmitted to the reproductive system by melatonin, a pineal...... hormone whose secretion is adjusted to night length. The photoperiodic variation in circulating melatonin has been shown to synchronize reproductive activity with seasons, but the mechanisms involved in this effect of melatonin were so far unknown. Recently we have observed that Kiss1 mRNA level in the...

  20. Uptake of indocyanine green by hamster sebaceous glands

    Science.gov (United States)

    McMillan, Kathleen; Lo, Kai-Ming; Wang, Zhi

    2001-05-01

    Photothermal injury to the sebaceous glands is a potential curative treatment for the common skin disease acne vulgaris. Accumulation of the exogenous chromophore indocyanine green in the sebaceous glands may be accomplished using an emulsion or liposomal formulation applied to the skin surface. An emulsion containing 0.09% by weight indocyanine green (ICG) was applied to the epidermis of hamster ears ex vivo and the flank organ in vivo. Fluorescence microscopy demonstrated selective accumulation of ICG in the underlying sebaceous glands. The concentration of ICG that may be expected to accumulate in sebaceous glands of humans was then estimated on the basis of the gland size and orifice area, for the case of topical application of a more concentrated 1% ICG liposomal formulation. Monte Carlo modeling and heat transfer calculations showed that the sebaceous glands containing the exogenous chromophore may be selectively damaged by pulsed 810 nm laser radiation in conjunction with cryogen spray cooling.

  1. Fluoxetine disrupts motivation and GABAergic signaling in adolescent female hamsters.

    Science.gov (United States)

    Shannonhouse, John L; DuBois, Dustin W; Fincher, Annette S; Vela, Alejandra M; Henry, Morgan M; Wellman, Paul J; Frye, Gerald D; Morgan, Caurnel

    2016-08-01

    Initial antidepressant treatment can paradoxically worsen symptoms in depressed adolescents by undetermined mechanisms. Interestingly, antidepressants modulate GABAA receptors, which mediate paradoxical effects of other therapeutic drugs, particularly in females. Although the neuroanatomic site of action for this paradox is unknown, elevated GABAA receptor signaling in the nucleus accumbens can disrupt motivation. We assessed fluoxetine's effects on motivated behaviors in pubescent female hamsters - anhedonia in the reward investigational preference (RIP) test as well as anxiety in the anxiety-related feeding/exploration conflict (AFEC) test. We also assessed accumbal signaling by RT-PCR and electrophysiology. Fluoxetine initially worsened motivated behaviors at puberty, relative to adulthood. It also failed to improve these behaviors as pubescent hamsters transitioned into adulthood. Low accumbal mRNA levels of multiple GABAA receptor subunits and GABA-synthesizing enzyme, GAD67, assessed by RT-PCR, suggested low GABAergic tone at puberty. Nonetheless, rapid fluoxetine-induced reductions of α5GABAA receptor and BDNF mRNA levels at puberty were consistent with age-related differences in GABAergic responses to fluoxetine and disruption of the motivational state. Whole-cell patch clamping of accumbal slices also suggested low GABAergic tone by the low amplitude of miniature inhibitory postsynaptic currents (mIPSCs) at puberty. It also confirmed age-related differences in GABAergic responses to fluoxetine. Specifically, fluoxetine potentiated mIPSC amplitude and frequency at puberty, but attenuated the amplitude during adulthood. These results implicate GABAergic tone and GABAA receptor plasticity in adverse motivational responses and resistance to fluoxetine during adolescence. PMID:27068049

  2. Retention of inhaled particles in hamsters with pulmonary fibrosis

    International Nuclear Information System (INIS)

    Aerosol retention was studied in hamsters 30, 60, and 90 days after the initiation of interstitial pulmonary fibrosis by a combination of bleomycin (bleo), 0.16 U/100 g body weight given intratracheally, and O2, for 72 h. Groups of bleo-O2-treated and control animals were exposed (awake) for 25 min to a 99mTc-labeled insoluble aerosol (activity median aerodynamic diameter, 0.45 micron; geometric standard deviation, 1.3). Within 5 min after exposure, the hamsters were killed and their lungs were excised and dried at total lung capacity, and sliced into 1-mm sections. Slices were dissected into pieces, and an evenness index (EI) was calculated for each piece (formula: see text). With uniformity of retention, all Els would be 1. The distribution of Els in control animals had a mean of 1.0 and a SD of 0.27; 0% of the Els were less than or equal to 0.20. Total retention diminished and was less uniform in bleo-O2-treated animals. At 30 days, the SD increased to 0.62, and 6% of the Els were less than or equal to 0.20. At 60 and 90 days, nonuniformity decreased but was still greater than that in the control animals (SD60 . 0.42, SD90 . 0.36). When examined histologically, individual pieces with low Els had more disease than those with high Els. Local decreases in compliance caused by fibrosis may have altered regional ventilation and retention. Our data also correlate with the progression of fibrosis from a focal lesion at 30 days to a more diffuse lesion at 90 days

  3. Photoperiod Regulates vgf-Derived Peptide Processing in Siberian Hamsters.

    Science.gov (United States)

    Noli, Barbara; Brancia, Carla; Pilleri, Roberta; D'Amato, Filomena; Messana, Irene; Manconi, Barbara; Ebling, Francis J P; Ferri, Gian-Luca; Cocco, Cristina

    2015-01-01

    VGF mRNA is induced in specific hypothalamic areas of the Siberian hamster upon exposure to short photoperiods, which is associated with a seasonal decrease in appetite and weight loss. Processing of VGF generates multiple bioactive peptides, so the objective of this study was to determine the profile of the VGF-derived peptides in the brain, pituitary and plasma from Siberian hamsters, and to establish whether differential processing might occur in the short day lean state versus long day fat. Antisera against short sequences at the C- or N- termini of proVGF, as well as against NERP-1, TPGH and TLQP peptides, were used for analyses of tissues, and both immunohistochemistry and enzyme linked immunosorbent assay (ELISA) coupled with high-performance liquid (HPLC) or gel chromatography were carried out. VGF peptide immunoreactivity was found within cortex cholinergic perikarya, in multiple hypothalamic nuclei, including those containing vasopressin, and in pituitary gonadotrophs. ELISA revealed that exposure to short day photoperiod led to a down-regulation of VGF immunoreactivity in the cortex, and a less pronounced decrease in the hypothalamus and pituitary, while the plasma VGF levels were not affected by the photoperiod. HPLC and gel chromatography both confirmed the presence of multiple VGF-derived peptides in these tissues, while gel chromatography showed the presence of the VGF precursor in all tissues tested except for the cortex. These observations are consistent with the view that VGF-derived peptides have pleiotropic actions related to changing photoperiod, possibly by regulating cholinergic systems in the cortex, vasopressin hypothalamic pathways, and the reproductive axis.

  4. Photoperiod Regulates vgf-Derived Peptide Processing in Siberian Hamsters.

    Directory of Open Access Journals (Sweden)

    Barbara Noli

    Full Text Available VGF mRNA is induced in specific hypothalamic areas of the Siberian hamster upon exposure to short photoperiods, which is associated with a seasonal decrease in appetite and weight loss. Processing of VGF generates multiple bioactive peptides, so the objective of this study was to determine the profile of the VGF-derived peptides in the brain, pituitary and plasma from Siberian hamsters, and to establish whether differential processing might occur in the short day lean state versus long day fat. Antisera against short sequences at the C- or N- termini of proVGF, as well as against NERP-1, TPGH and TLQP peptides, were used for analyses of tissues, and both immunohistochemistry and enzyme linked immunosorbent assay (ELISA coupled with high-performance liquid (HPLC or gel chromatography were carried out. VGF peptide immunoreactivity was found within cortex cholinergic perikarya, in multiple hypothalamic nuclei, including those containing vasopressin, and in pituitary gonadotrophs. ELISA revealed that exposure to short day photoperiod led to a down-regulation of VGF immunoreactivity in the cortex, and a less pronounced decrease in the hypothalamus and pituitary, while the plasma VGF levels were not affected by the photoperiod. HPLC and gel chromatography both confirmed the presence of multiple VGF-derived peptides in these tissues, while gel chromatography showed the presence of the VGF precursor in all tissues tested except for the cortex. These observations are consistent with the view that VGF-derived peptides have pleiotropic actions related to changing photoperiod, possibly by regulating cholinergic systems in the cortex, vasopressin hypothalamic pathways, and the reproductive axis.

  5. INVESTIGATION OF POSSIBLE AGE EFFECTS ON MEIOTIC CHROMOSOMAL RECOMBINATION AND SEGREGATION IN ARMENIAN HAMSTER SPERMATOCYTES

    Science.gov (United States)

    Male Armenian hamsters (Cricetulus migratorius; 2N:22) were evaluated for age effects upon meiotic recombination and aneuploidy incidence. Primary spermatocytes from young and old animals revealed similar chiasma frequencies. The incidence of terminal-type chiasmata in sex bivale...

  6. Seasonal adaptation of dwarf hamsters (Genus Phodopus): differences between species and their geographic origin.

    Science.gov (United States)

    Müller, D; Hauer, J; Schöttner, K; Fritzsche, P; Weinert, D

    2015-12-01

    The genus Phodopus consists of three species--P. campbelli (Pc), P. sungorus (Ps), and P. roborovskii (Pr). They inhabit steppes, semi-deserts, and deserts in continental Asia with a climate changing from a moderate to a hard Continental one with extreme daily and seasonal variations. These different environmental challenges are likely to have consequences for hamsters' morphology, physiology, and behavior. Hamsters of all three species were investigated during the course of the year in the laboratory though using natural lighting and temperature conditions. Motor activity and body temperature were measured continuously, and body mass, testes size, and fur coloration every 1-2 weeks. With regard to the pattern of activity, nearly twice as many Pc as Ps hamsters (25 vs. 14%) failed to respond to changes of photoperiod, whereas all Pr hamsters did. Body mass and testes size were high in summer and low in winter, with the biggest relative change in Ps and the lowest in Pr hamsters. Changes of fur coloration were found in Ps hamsters only. All responding animals (that is excluding Pr), exhibited regular torpor bouts during the short winter days. In autumn, seasonal changes started considerably earlier in Ps hamsters. To investigate the putative causes of these different time courses, a further experiment was performed, to identify the critical photoperiod. Hamsters were kept for 10 weeks under different photoperiods, changing from 16 to 8 h light per day. Motor activity was recorded continuously, to identify responding and non-responding animals. Body mass was measured at the beginning and the end of the experiment, testes mass only at the end. The critical photoperiod was found to be similar in all three species. Though in a further experiment, Pc and Pr hamsters showed a delayed response, whereas the changes in Ps hamsters started immediately following transfer to short-day conditions. The results show that interspecific differences in seasonal adaptation exist, even

  7. Seasonal pelage changes are synchronized by simulated natural photoperiods in Siberian hamsters (Phodopus sungorus)

    OpenAIRE

    Butler, Matthew P.; Zucker, Irving

    2009-01-01

    The extent to which changing day lengths synchronize the seasonal molt was assessed in nine cohorts of male and female Siberian hamsters (Phodopus sungorus) born into a simulated natural photoperiod (SNP) beginning 4 weeks before and ending 12 weeks after the summer solstice. Hamsters in early cohorts displayed rapid somatic and gonadal growth and early puberty, whereas those in later cohorts delayed puberty until the next spring. Despite the varying birth dates and puberty strategies, the se...

  8. Aflatoxin B1 metabolism by 3-methylcholanthrene-induced hamster hepatic cytochrome P-450s.

    Science.gov (United States)

    Lai, T S; Chiang, J Y

    1990-01-01

    We have studied the activation of aflatoxin B1 by hamster liver microsomes and purified hamster cytochrome P-450 isozymes using a umu mutagen test. The hamster liver microsomes or S-9 fractions were much more active than rat liver microsomes or S-9 fractions in the activation of umu gene expression by aflatoxin B1 metabolites. 3-Methyl-cholanthrene treatment increased aflatoxin B1 activation by hamster liver microsomes. Two major 3-methylcholanthrene-inducible cytochrome P-450 isozymes, P-450 MC1 (IIA) and P-450 MC4 (IA2), were purified from 3-methylcholanthrene-treated hamster liver microsomes, and the metabolism of aflatoxin B1 by these two cytochromes was studied. In the reconstituted enzyme system, both P-450 MC1 and P-450 MC4 were highly active in the activation of aflatoxin B1, and antibodies against these P-450s specifically inhibited these activities. Antibody against P-450 MC1 inhibited the activation of aflatoxin B1 by 20% in the presence of 3-methyl-cholanthrene-treated hamster liver microsomes. In contrast, antibody against P-450 MC4 stimulated the activity by 175%. These results indicated that hamster P-450 MC1 might convert aflatoxin B1 to more toxic metabolite(s), whereas P-450 MC4 might convert aflatoxin B1 to less toxic metabolite(s), than aflatoxin B1 in liver microsomes. The metabolite(s) produced by both hamster cytochrome P-450 MC1 and MC4 were genotoxic in the umu mutagen test. PMID:2126562

  9. Use of hamster as a model to study diet-induced atherosclerosis

    Directory of Open Access Journals (Sweden)

    Lichtenstein Alice H

    2010-12-01

    Full Text Available Abstract Golden-Syrian hamsters have been used as an animal model to assess diet-induced atherosclerosis since the early 1980s. Advantages appeared to include a low rate of endogenous cholesterol synthesis, receptor-mediated uptake of LDL cholesterol, cholesteryl ester transfer protein activity, hepatic apoB-100 and intestinal apoB-48 secretion, and uptake of the majority of LDL cholesterol via the LDL receptor pathway. Early work suggested hamsters fed high cholesterol and saturated fat diets responded similarly to humans in terms of lipoprotein metabolism and aortic lesion morphology. Recent work has not consistently replicated these findings. Reviewed was the literature related to controlled hamster feeding studies that assessed the effect of strain, background diet (non-purified, semi-purified and dietary perturbation (cholesterol and/or fat on plasma lipoprotein profiles and atherosclerotic lesion formation. F1B hamsters fed a non-purified cholesterol/fat-supplemented diet had more atherogenic lipoprotein profiles (nHDL-C > HDL-C than other hamster strains or hamsters fed cholesterol/fat-supplemented semi-purified diets. However, fat type; saturated (SFA, monounsaturated or n-6 polyunsaturated (PUFA had less of an effect on plasma lipoprotein concentrations. Cholesterol- and fish oil-supplemented semi-purified diets yielded highly variable results when compared to SFA or n-6 PUFA, which were antithetical to responses observed in humans. Dietary cholesterol and fat resulted in inconsistent effects on aortic lipid accumulation. No hamster strain was reported to consistently develop lesions regardless of background diet, dietary cholesterol or dietary fat type amount. In conclusion, at this time the Golden-Syrian hamster does not appear to be a useful model to determine the mechanism(s of diet-induced development of atherosclerotic lesions.

  10. Developmental Changes in the ECG of a Hamster Model of Muscular Dystrophy and Heart Failure

    OpenAIRE

    ThomasGerardHampton; AjitKale; HemmiBhagavan

    2012-01-01

    Aberrant autonomic signaling is being increasingly recognized as an important symptom in neuromuscular disorders. The delta-sarcoglycan-deficient BIO TO-2 hamster is recognized as a good model for studying mechanistic pathways and sequelae in muscular dystrophy and heart failure, including autonomic nervous system dysfunction. Recent studies using the TO-2 hamster model have provided promising preclinical results demonstrating the efficacy of gene therapy to treat skeletal muscle weakness a...

  11. Effects of propionyl-L-carnitine on ischemia-reperfusion injury in hamster cheek pouch microcirculation.

    OpenAIRE

    DomingaLapi; LinaSabatino; GiovannaAltobelli

    2010-01-01

    Background and Purpose Propionyl-L-carnitine (pLc) exerts protective effects in different experimental models of ischemia-reperfusion (I/R). The aim of the present study was to assess the effects of intravenously and topically applied pLc on microvascular permeability increase induced by I/R in the hamster check pouch preparation. Methods The hamster check pouch microcirculation was visualized by fluorescence microscopy. Microvascular permeability, leukocyte adhesion to venular walls, perfus...

  12. Adaptation to short photoperiods augments circadian food anticipatory activity in Siberian hamsters

    OpenAIRE

    Bradley, Sean P.; Prendergast, Brian J.

    2014-01-01

    Both the light-dark cycle and the timing of food intake can entrain circadian rhythms. Entrainment to food is mediated by a food entrainable circadian oscillator (FEO) that is formally and mechanistically separable from the hypothalamic light-entrainable oscillator. This experiment examined whether seasonal changes in day length affect the function of the FEO in male Siberian hamsters (Phodopus sungorus). Hamsters housed in long (LD; 15 h light/day) or short (SD; 9 h light/day) photoperiods w...

  13. Leptin mediates seasonal variation in some but not all symptoms of sickness in Siberian hamsters.

    Science.gov (United States)

    Carlton, Elizabeth D; Demas, Gregory E

    2014-11-01

    Many seasonally breeding species, including Siberian hamsters (Phodopus sungorus), exhibit seasonal variation in sickness responses. One hypothesis regarding the mechanism of this variation is that sickness intensity tracks an animal's energetic state, such that sickness is attenuated in the season that an animal has the lowest fat stores. Energetic state may be signaled via leptin, an adipose hormone that provides a signal of fat stores. Siberian hamsters respond to extended housing in short, winter-like days by reducing fat stores and leptin levels, relative to those housed in long, summer-like days. Sickness responses are also attenuated in short-day hamsters as compared to long-day hamsters. We hypothesized that leptin provides a physiological signal by which seasonally breeding animals modulate sickness responses, such that animals with higher leptin levels show increased sickness intensity. To test this, we provided short-day hamsters with a long-day-like leptin signal and assessed their responses to lipopolysaccharide (LPS), a sickness-inducing antigen. We compared these responses to short-day vehicle-, long-day vehicle-, and long-day leptin-treated hamsters. Unexpectedly, LPS induced a hypothermic response (rather than fever) in all groups. Short-day vehicle-treated hamsters exhibited the greatest LPS-induced hypothermia, and leptin treatment attenuated this response, making hypothermia more long-day-like. Contrary to our hypothesis, short-day leptin-treated hamsters showed the least pronounced LPS-induced anorexia among all groups. These results suggest that leptin may mediate some but not all aspects of seasonal sickness variation in this species. Future studies should be targeted at determining roles of other energetic hormones in regulating seasonal sickness response variation.

  14. Male Syrian Hamsters Demonstrate a Conditioned Place Preference for Sexual Behavior and Female Chemosensory Stimuli

    OpenAIRE

    Bell, Margaret R.; Meerts, Sarah H.; Sisk, Cheryl L.

    2010-01-01

    Sexual behavior is a natural reward for many rodent species, and it often includes chemosensory-directed components. Chemosensory stimuli themselves may also be rewarding. Conditioned place preference (CPP) is one paradigm frequently used to test the rewarding properties of a range of stimuli. Males and females of several rodent species show a CPP for sexual behavior, however, it is currently unknown whether sexual behavior can induce a CPP in male Syrian hamsters. As male Syrian hamsters are...

  15. Experimental infection of hamsters with avian paramyxovirus serotypes 1 to 9

    Directory of Open Access Journals (Sweden)

    Samuel Arthur S

    2011-02-01

    Full Text Available Abstract Avian paramyxoviruses (APMVs are frequently isolated from domestic and wild birds throughout the world and are separated into nine serotypes (APMV-1 to -9. Only in the case of APMV-1, the infection of non-avian species has been investigated. The APMVs presently are being considered as human vaccine vectors. In this study, we evaluated the replication and pathogenicity of all nine APMV serotypes in hamsters. The hamsters were inoculated intranasally with each virus and monitored for clinical disease, pathology, histopathology, virus replication, and seroconversion. On the basis of one or more of these criteria, each of the APMV serotypes was found to replicate in hamsters. The APMVs produced mild or inapparent clinical signs in hamsters except for APMV-9, which produced moderate disease. Gross lesions were observed over the pulmonary surface of hamsters infected with APMV-2 & -3, which showed petechial and ecchymotic hemorrhages, respectively. Replication of all of the APMVs except APMV-5 was confirmed in the nasal turbinates and lungs, indicating a tropism for the respiratory tract. Histologically, the infection resulted in lung lesions consistent with bronchointerstitial pneumonia of varying severity and nasal turbinates with blunting or loss of cilia of the epithelium lining the nasal septa. The majority of APMV-infected hamsters exhibited transient histological lesions that self resolved by 14 days post infection (dpi. All of the hamsters infected with the APMVs produced serotype-specific HI or neutralizing antibodies, confirming virus replication. Taken together, these results demonstrate that all nine known APMV serotypes are capable of replicating in hamsters with minimal disease and pathology.

  16. Engagement of NKG2D on bystander memory CD8 T cells promotes increased immunopathology following Leishmania major infection.

    Directory of Open Access Journals (Sweden)

    Erika J Crosby

    2014-02-01

    Full Text Available One of the hallmarks of adaptive immunity is the development of a long-term pathogen specific memory response. While persistent memory T cells certainly impact the immune response during a secondary challenge, their role in unrelated infections is less clear. To address this issue, we utilized lymphocytic choriomeningitis virus (LCMV and Listeria monocytogenes immune mice to investigate whether bystander memory T cells influence Leishmania major infection. Despite similar parasite burdens, LCMV and Listeria immune mice exhibited a significant increase in leishmanial lesion size compared to mice infected with L. major alone. This increased lesion size was due to a severe inflammatory response, consisting not only of monocytes and neutrophils, but also significantly more CD8 T cells. Many of the CD8 T cells were LCMV specific and expressed gzmB and NKG2D, but unexpectedly expressed very little IFN-γ. Moreover, if CD8 T cells were depleted in LCMV immune mice prior to challenge with L. major, the increase in lesion size was lost. Strikingly, treating with NKG2D blocking antibodies abrogated the increased immunopathology observed in LCMV immune mice, showing that NKG2D engagement on LCMV specific memory CD8 T cells was required for the observed phenotype. These results indicate that bystander memory CD8 T cells can participate in an unrelated immune response and induce immunopathology through an NKG2D dependent mechanism without providing increased protection.

  17. Contribution of radiation-induced, nitric oxide-mediated bystander effect to radiation-induced adaptive response.

    Science.gov (United States)

    Matsumoto, H.; Ohnishi, T.

    There has been a recent upsurge of interest in radiation-induced adaptive response and bystander effect which are specific modes in stress response to low-dose low-dose rate radiation Recently we found that the accumulation of inducible nitric oxide NO synthase iNOS in wt p53 cells was induced by chronic irradiation with gamma rays followed by acute irradiation with X-rays but not by each one resulting in an increase in nitrite concentrations of medium It is suggested that the accumulation of iNOS may be due to the depression of acute irradiation-induced p53 functions by pre-chronic irradiation In addition we found that the radiosensitivity of wt p53 cells against acute irradiation with X-rays was reduced after chronic irradiation with gamma rays This reduction of radiosensitivity of wt p53 cells was nearly completely suppressed by the addition of NO scavenger carboxy-PTIO to the medium This reduction of radiosensitivity of wt p53 cells is just radiation-induced adaptive response suggesting that NO-mediated bystander effect may considerably contribute to adaptive response induced by radiation

  18. Neoplastic transformation in vitro by low doses of ionizing radiation: Role of adaptive response and bystander effects

    Energy Technology Data Exchange (ETDEWEB)

    Ko, M. [Department of Radiation Oncology, University of California Irvine, Irvine, CA 92697 (United States); Lao, X.-Y. [Department of Radiation Oncology, University of California Irvine, Irvine, CA 92697 (United States); Kapadia, R. [Department of Radiation Oncology, University of California Irvine, Irvine, CA 92697 (United States); Elmore, E. [Department of Radiation Oncology, University of California Irvine, Irvine, CA 92697 (United States); Redpath, J.L. [Department of Radiation Oncology, University of California Irvine, Irvine, CA 92697 (United States)]. E-mail: jlredpat@uci.edu

    2006-05-11

    The shape of the dose-response curve for cancer induction by low doses of ionizing radiation is of critical importance to the assessment of cancer risk at such doses. Epidemiologic analyses are limited by sensitivity to doses typically greater than 50-100 mGy for low LET radiation. Laboratory studies allow for the examination of lower doses using cancer-relevant endpoints. One such endpoint is neoplastic transformation in vitro. It is known that this endpoint is responsive to both adaptive response and bystander effects. The relative balance of these processes is likely to play an important role in determining the shape of the dose-response curve at low doses. A factor that may influence this balance is cell density at time of irradiation. The findings reported in this paper indicate that the transformation suppressive effect of low doses previously seen following irradiation of sub-confluent cultures, and attributed to an adaptive response, is reduced for irradiated confluent cultures. However, even under these conditions designed to optimize the role of bystander effects the data do not fit a linear no-threshold model and are still consistent with the notion of a threshold dose for neoplastic transformation in vitro by low LET radiation.

  19. Autoradiographic localization of tritiated dihydrotestosterone in the flank organ of the albino hamster

    International Nuclear Information System (INIS)

    In the hamster flank organ, the growth of hair and growth of sebaceous glands are androgen-dependent functions. Although dihydrotestosterone (DHT) is known to be a potent stimulator of flank organ growth, there is no information about localization of DHT receptor sites in this organ. The purpose of this study was to use steroid autoradiography to localize DHT receptors in the hamster flank organ. Because steroid hormones are functional when translocated to nuclear receptors, nuclear localization by autoradiography defines receptor sites. In order to be able to visualize autoradiographic grains from radiolabeled androgens around hair follicles, albino hamsters were studied to avoid confusion between the grains and pigment granules which are abundant in the more common Golden Syrian hamster. Mature male hamsters castrated 24 hours earlier were given tritium-labeled dihydrotestosterone ( [3H]DHT). Using the technique of thaw-mount steroid autoradiography, 4-micron unfixed frozen sections were mounted in the dark onto emulsion-coated glass slides and allowed to develop for 4-6 months. [3H]DHT was found to be concentrated over sebocyte nuclei. The label was present peripherally as well as in differentiating sebocytes. There was no nuclear localization of [3H]DHT in animals pretreated with excessive quantities of unlabeled DHT. Steroid metabolites of [3H] DHT were assessed by thin-layer chromatography in paired tissue samples. Most of the label remained with DHT. Uptake was inhibited in the flank organ of hamsters pretreated with unlabeled DHT

  20. Individual differences in circadian waveform of Siberian hamsters under multiple lighting conditions.

    Science.gov (United States)

    Evans, Jennifer A; Elliott, Jeffrey A; Gorman, Michael R

    2012-10-01

    Because the circadian clock in the mammalian brain derives from a network of interacting cellular oscillators, characterizing the nature and bases of circadian coupling is fundamental to understanding how the pacemaker operates. Various phenomena involving plasticity in circadian waveform have been theorized to reflect changes in oscillator coupling; however, it remains unclear whether these different behavioral paradigms reference a unitary underlying process. To test whether disparate coupling assays index a common mechanism, we examined whether there is covariation among behavioral responses to various lighting conditions that produce changes in circadian waveform. Siberian hamsters, Phodopus sungorus, were transferred from long to short photoperiods to distinguish short photoperiod responders (SP-R) from nonresponders (SP-NR). Short photoperiod chronotyped hamsters were subsequently transferred, along with unselected controls, to 24-h light:dark:light: dark cycles (LDLD) with dim nighttime illumination, a procedure that induces bifurcated entrainment. Under LDLD, SP-R hamsters were more likely to bifurcate their rhythms than were SP-NR hamsters or unselected controls. After transfer from LDLD to constant dim light, SP-R hamsters were also more likely to become arrhythmic compared to SP-NR hamsters and unselected controls. In contrast, short photoperiod chronotype did not influence more transient changes in circadian waveform. The present data reveal a clear relationship in the plasticity of circadian waveform across 3 distinct lighting conditions, suggesting a common mechanism wherein individual differences reflect variation in circadian coupling.

  1. Beneficial effects of noni (Morinda citrifolia L.) juice on livers of high-fat dietary hamsters.

    Science.gov (United States)

    Lin, Yi-Ling; Chang, Yuan-Yen; Yang, Deng-Jye; Tzang, Bor-Show; Chen, Yi-Chen

    2013-09-01

    Polyphenols in noni juice (NJ) are mainly composed of phenolic acids, mainly gentisic, p-hydroxybenoic, and chlorogenic acids. To investigate the beneficial effects of NJ on the liver, hamsters were fed with two diets, normal-fat and high-fat diets. Furthermore, high-fat dietary hamsters were received distilled water, and 3, 6, and 9 mL NJ/kg BW, respectively. After a 6-week feeding period, the increased (p<0.05) sizes of liver and visceral fat in high-fat dietary hamsters compared to the control hamsters were ameliorated (p<0.05) by NJ supplementation. NJ also decreased (p<0.05) serum/liver lipids but enhanced (p<0.05) daily faecal lipid/bile acid outputs in the high-fat dietary hamsters. High-fat dietary hamsters supplemented with NJ had higher (p<0.05) liver antioxidant capacities but lowered (p<0.05) liver iNOS, COX-2, TNF-α, and IL-1β expressions, gelatinolytic levels of MMP9, and serum ALT values compared to those without NJ. Hence, NJ protects liver against a high-fat dietary habit via regulations of antioxidative and anti-inflammatory responses.

  2. Pharmacokinetics and the bystander effect in CD::UPRT/5-FC bi-gene therapy of glioma

    Institute of Scientific and Technical Information of China (English)

    SHI De-zhi; HU Wei-xing; LI Li-xin; CHEN Gong; WEI Dong; GU Pei-yuan

    2009-01-01

    Background Cytosine deaminase (CD) converts 5-fluorocytosine (5-FC) to 5-fluorouracil (5-FU) in CD/5-FC gene therapy, 5-FU will be mostly converted into nontoxic β-alanine without uracil phosphoribosyltransferase (UPRT). UPRT catalyzes the conversion of 5-FU to 5-fluorouridine monophosphate, which directly kills CD::UPRT-expressing ceils and surrounding cells via the bystander effect. But the pharmacokinetics and the bystander effect of CD::UPRT/5-FC has not been verified in vivo and in vitro. Before the CD::UPRT/5-FC bi-gene therapy system is used in clinical trial, it is essential to monitor the transgene expression and function in vivo. Thus, we developed a preclinical tumor model to investigate the feasibility of using 19F-magnetic resonance spectroscopy (19F-MRS) and optical imaging to measure non-invasive CD and UPRT expression and its bystander effect.Methods C6 and C6-CD::UPRT cells were cultured with 5-FC. The medium, cells and their mixture were analyzed by 19F-MRS. Rats with intracranial xenografted encephalic C6-CD::UPRT glioma were injected intraperitoneally with 5-FC and their 19F-MRS spectra recorded. Then the pharmacokinetics of 5-FC was proved. Mixtures of C6 and C6-CD::UPRT cells at different ratios were cultured with 5-FC and the cytotoxic efficacy and survival rate of cells recorded. To determine the mechanism of the bystander effect, the culture media from cell comprising 25% and 75% C6-CD::UPRT cells were examined by19F-MRS. A comparative study of mean was performed using analysis of variance (ANOVA). Results 19F-MRS on samples from C6-CD::UPRT cells cultured with 5-FC showed three broad resonance signals corresponding to 5-FC, 5-FU and fluorinated nucleotides (F-Nuctd). For the C6 mixture, only the 5-FC peak was detected. In vivo serial 19F-MRS spectra showed a strong 5-FC peak and a weak 5-FU peak at 20 minutes after 5-FC injection. The 5-FU concentration reached a maximum at about 50 minutes. The F-Nuctd signal appeared after about I hour

  3. Chinese Confucianism

    OpenAIRE

    Macfarlane, Alan; Cullen, Christopher

    2004-01-01

    Confucianism has deeply influenced Chinese civilization. Christopher Cullen describes its effect on education, social structure and knowledge over the past centuries, against the backdrop of a Confucian building in Beijing.

  4. DNA damaging bystander signalling from stem cells, cancer cells and fibroblasts after Cr(VI) exposure and its dependence on telomerase

    Energy Technology Data Exchange (ETDEWEB)

    Cogan, Nicola [Bristol Implant Research Centre, University of Bristol, Bristol, BS10 5NB (United Kingdom); Baird, Duncan M. [Department of Pathology School of Medicine, Cardiff University, Henry Wellcome Building for Biomedical Research in Wales, Heath Park, Cardiff, CF14 4XN (United Kingdom); Phillips, Ryan [Bristol Implant Research Centre, University of Bristol, Bristol, BS10 5NB (United Kingdom); Crompton, Lucy A.; Caldwell, Maeve A. [Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Bristol, BS1 3NY (United Kingdom); Rubio, Miguel A. [Center of Regenerative Medicine in Barcelona, CMRB Dr. Aiguader, 88, 7th Floor, 08003 Barcelona (Spain); Newson, Roger [Radiation and Environmental Science Centre, Focas Institute, Dublin Institute of Technology, Dublin 2 (Ireland); Lyng, Fiona [National Heart and Lung Institute, Imperial College London, London, SW7 2AZ (United Kingdom); Case, C. Patrick, E-mail: c.p.case@bristol.ac.uk [Bristol Implant Research Centre, University of Bristol, Bristol, BS10 5NB (United Kingdom)

    2010-01-05

    The bystander effect is a feature of low dose radiation exposure and is characterized by a signaling process from irradiated cells to non irradiated cells, which causes DNA and chromosome damage in these 'nearest neighbour' cells. Here we show that a low and short dose of Cr(VI) can induce stem cells, cancer cells and fibroblasts to chronically secrete bystander signals, which cause DNA damage in neighboring cells. The Cr(VI) induced bystander signaling depended on the telomerase status of either cell. Telomerase negative fibroblasts were able to receive DNA damaging signals from telomerase positive or negative fibroblasts or telomerase positive cancer cells. However telomerase positive fibroblasts were resistant to signals from Cr(VI) exposed telomerase positive fibroblasts or cancer cells. Human embryonic stem cells, with positive Oct4 staining as a marker of pluripotency, showed no significant increase of DNA damage from adjacent Cr and mitomycin C exposed fibroblasts whilst those cells that were negatively stained did. This selectivity of DNA damaging bystander signaling could be an important consideration in developing therapies against cancer and in the safety and effectiveness of tissue engineering and transplantation using stem cells.

  5. Bystander autophagy mediated by radiation-induced exosomal miR-7-5p in non-targeted human bronchial epithelial cells.

    Science.gov (United States)

    Song, Man; Wang, Yu; Shang, Zeng-Fu; Liu, Xiao-Dan; Xie, Da-Fei; Wang, Qi; Guan, Hua; Zhou, Ping-Kun

    2016-01-01

    Radiation-induced bystander effect (RIBE) describes a set of biological effects in non-targeted cells that receive bystander signals from the irradiated cells. RIBE brings potential hazards to adjacent normal tissues in radiotherapy, and imparts a higher risk than previously thought. Excessive release of some substances from irradiated cells into extracellular microenvironment has a deleterious effect. For example, cytokines and reactive oxygen species have been confirmed to be involved in RIBE process via extracellular medium or gap junctions. However, RIBE-mediating signals and intercellular communication pathways are incompletely characterized. Here, we first identified a set of differentially expressed miRNAs in the exosomes collected from 2 Gy irradiated human bronchial epithelial BEP2D cells, from which miR-7-5p was found to induce autophagy in recipient cells. This exosome-mediated autophagy was significantly attenuated by miR-7-5p inhibitor. Moreover, our data demonstrated that autophagy induced by exosomal miR-7-5p was associated with EGFR/Akt/mTOR signaling pathway. Together, our results support the involvement of secretive exosomes in propagation of RIBE signals to bystander cells. The exosomes-containing miR-7-5p is a crucial mediator of bystander autophagy. PMID:27417393

  6. DNA damaging bystander signalling from stem cells, cancer cells and fibroblasts after Cr(VI) exposure and its dependence on telomerase

    International Nuclear Information System (INIS)

    The bystander effect is a feature of low dose radiation exposure and is characterized by a signaling process from irradiated cells to non irradiated cells, which causes DNA and chromosome damage in these 'nearest neighbour' cells. Here we show that a low and short dose of Cr(VI) can induce stem cells, cancer cells and fibroblasts to chronically secrete bystander signals, which cause DNA damage in neighboring cells. The Cr(VI) induced bystander signaling depended on the telomerase status of either cell. Telomerase negative fibroblasts were able to receive DNA damaging signals from telomerase positive or negative fibroblasts or telomerase positive cancer cells. However telomerase positive fibroblasts were resistant to signals from Cr(VI) exposed telomerase positive fibroblasts or cancer cells. Human embryonic stem cells, with positive Oct4 staining as a marker of pluripotency, showed no significant increase of DNA damage from adjacent Cr and mitomycin C exposed fibroblasts whilst those cells that were negatively stained did. This selectivity of DNA damaging bystander signaling could be an important consideration in developing therapies against cancer and in the safety and effectiveness of tissue engineering and transplantation using stem cells.

  7. Hamster-Adapted Sin Nombre Virus Causes Disseminated Infection and Efficiently Replicates in Pulmonary Endothelial Cells without Signs of Disease

    OpenAIRE

    Safronetz, David; Prescott, Joseph; Haddock, Elaine; Scott, Dana P.; Feldmann, Heinz; Ebihara, Hideki

    2013-01-01

    To date, a laboratory animal model for the study of Sin Nombre virus (SNV) infection or associated disease has not been described. Unlike infection with Andes virus, which causes lethal hantavirus pulmonary syndrome (HPS)-like disease in hamsters, SNV infection is short-lived, with no viremia and little dissemination. Here we investigated the effect of passaging SNV in hamsters. We found that a host-adapted SNV achieves prolonged and disseminated infection in hamsters, including efficient rep...

  8. Mechanisms and biological importance of photon-induced bystander responses. Do they have an impact on low-dose radiation responses

    International Nuclear Information System (INIS)

    Elucidating the biological effect of low linear energy transfer (LET), low-dose and/or low-dose-rate ionizing radiation is essential in ensuring radiation safety. Over the past two decades, non-targeted effects, which are not only a direct consequence of radiation-induced initial lesions produced in cellular DNA but also of intra- and inter-cellular communications involving both targeted and non-targeted cells, have been reported and are currently defining a new paradigm in radiation biology. These effects include radiation-induced adaptive response, low-dose hypersensitivity, genomic instability, and radiation-induced bystander response (RIBR). RIBR is generally defined as a cellular response that is induced in non-irradiated cells that receive bystander signals from directly irradiated cells. RIBR could thus play an important biological role in low-dose irradiation conditions. However, this suggestion was mainly based on findings obtained using high-LET charged-particle radiations. The human population (especially the Japanese, who are exposed to lower doses of radon than the world average) is more frequently exposed to low-LET photons (X-rays or γ-rays) than to high-LET charged-particle radiation on a daily basis. There are currently a growing number of reports describing a distinguishing feature between photon-induced bystander response and high-LET RIBR. In particular, photon-induced by-stander response is strongly influenced by irradiation dose, the irradiated region of the targeted cells, and p53 status. The present review focuses on the photon-induced bystander response, and discusses its impact on the low-dose radiation effect. (author)

  9. DEVELOPMENT OF MICE AND HAMSTER EMBRYOS IN KSOMAA AND HECM-6 MEDIUM

    Directory of Open Access Journals (Sweden)

    Bayu Rosadi

    2008-12-01

    Full Text Available The purpose of the present study was to investigate the viability of mice and hamster embryos developed in Kalium Simplex Optimized Medium amino acid (KSOMaa and Hamster Embryo Culture Medium-6 (HECM-6 medium. Female DDY mice were superovulated by injection i.p. of 5 IU Pregnant Mare Serum Gonadotropine (PMSG and 5 IU Human Chorionic Gonadotropine (hCG in 48 h interval, hamster (Phodopus campbelli injected by 2.5 IU PMSG and 2.5 IU hCG 48 h later. Then females were mated with fertile males. Eight-cell embryos were recovered at day 3 after natural mating. The mice embryos were cultured in KSOMaa+5% NBCS (New Born Calf Serum (T1 and HECM-6+5% NBCS (T2, the hamster embryos were cultured in KSOMaa+5% NBCS (T3 and HECM-6 + 5% NBCS (T4 for further development at 37oC in a humidified atmosphere of 5% CO2 in air for 48 h. The examinations were replicated five times. The T1 embryos developed to compact morulla and early blastocyst 100% (140/140, 92.1% (129/140 to blastocyst and expanded blastocyst, and 22.9% (32/140 became hatching/hatched. The T3 reached 100% (60/60 to compact morulla and early blastocyst, 85.0% (51/60 blastocyst, and 48.3% (29/60 expanded blastocyst, no embryo observed hatching/hatced. The T2 embryos had more expanded blastocyst than T3 (P<0.05, hatching/hatched rate higher than T1 and T3 but lower than T4 (P<0.05. Shortly, KSOMaa enable to support 8-cell stage mice and hamster embryo, but the hamster embryo developed lower at expanded blastocyst stage. HECM-6 is more appropriate than KSOMaa to support 8-cell mice embryos development and suitable to develop 8-cell stage hamster embryos.

  10. Vomeronasal organ lesion disrupts social odor recognition, behaviors and fitness in golden hamsters.

    Science.gov (United States)

    Liu, Yingjuan; Zhang, Jinhua; Liu, Dingzhen; Zhang, Jianxu

    2014-06-01

    Most studies support the viewpoint that the vomeronasal organ has a profound effect on conspecific odor recognition, scent marking and mating behavior in the golden hamster (Mesocricetus auratus). However, the role of the vomeronasal organ in social odor recognition, social interaction and fitness is not well understood. Therefore, we conducted a series of behavioral and physiological tests to examine the referred points in golden hamster. We found that male hamsters with vomeronasal organ lesion showed no preference between a predator odor (the anal gland secretion of the Siberian weasels (Mustela sibirica) and putative female pheromone components (myristic acid and palmitic acid), but were still able to discriminate between these 2 kinds of odors. In behavioral tests of anxiety, we found that vomeronasal organ removal causes female hamsters to spend much less time in center grids and to cross fewer center grids and males to make fewer crossings between light and dark boxes than sham-operated controls. This indicates that a chronic vomeronasal organ lesion induced anxious responses in females. In aggressive behavioral tests, we found that a chronic vomeronasal organ lesion decreased agonistic behavior in female hamsters but not in males. The pup growth and litter size show no differences between the 2 groups. All together, our data suggested that vomeronasal organ ablation disrupted the olfactory recognition of social chemosignals in males, and induced anxiety-like and aggressive behavior changes in females. However, a vomeronasal organ lesion did not affect the reproductive capacity and fitness of hamsters. Our studies may have important implications concerning the role of the vomeronasal organ in golden hamsters and also in rodents. PMID:24952966

  11. Transmission of chronic wasting disease identifies a prion strain causing cachexia and heart infection in hamsters.

    Directory of Open Access Journals (Sweden)

    Richard A Bessen

    Full Text Available Chronic wasting disease (CWD is an emerging prion disease of free-ranging and captive cervids in North America. In this study we established a rodent model for CWD in Syrian golden hamsters that resemble key features of the disease in cervids including cachexia and infection of cardiac muscle. Following one to three serial passages of CWD from white-tailed deer into transgenic mice expressing the hamster prion protein gene, CWD was subsequently passaged into Syrian golden hamsters. In one passage line there were preclinical changes in locomotor activity and a loss of body mass prior to onset of subtle neurological symptoms around 340 days. The clinical symptoms included a prominent wasting disease, similar to cachexia, with a prolonged duration. Other features of CWD in hamsters that were similar to cervid CWD included the brain distribution of the disease-specific isoform of the prion protein, PrP(Sc, prion infection of the central and peripheral neuroendocrine system, and PrP(Sc deposition in cardiac muscle. There was also prominent PrP(Sc deposition in the nasal mucosa on the edge of the olfactory sensory epithelium with the lumen of the nasal airway that could have implications for CWD shedding into nasal secretions and disease transmission. Since the mechanism of wasting disease in prion diseases is unknown this hamster CWD model could provide a means to investigate the physiological basis of cachexia, which we propose is due to a prion-induced endocrinopathy. This prion disease phenotype has not been described in hamsters and we designate it as the 'wasting' or WST strain of hamster CWD.

  12. Identification, expression, and physiological functions of Siberian hamster gonadotropin-inhibitory hormone.

    Science.gov (United States)

    Ubuka, Takayoshi; Inoue, Kazuhiko; Fukuda, Yujiro; Mizuno, Takanobu; Ukena, Kazuyoshi; Kriegsfeld, Lance J; Tsutsui, Kazuyoshi

    2012-01-01

    Gonadotropin-inhibitory hormone (GnIH) is a hypothalamic neuropeptide that inhibits gonadotropin secretion in birds and mammals. To further understand its physiological roles in mammalian reproduction, we identified its precursor cDNA and endogenous mature peptides in the Siberian hamster brain. The Siberian hamster GnIH precursor cDNA encoded two RFamide-related peptide (RFRP) sequences. SPAPANKVPHSAANLPLRF-NH(2) (Siberian hamster RFRP-1) and TLSRVPSLPQRF-NH(2) (Siberian hamster RFRP-3) were confirmed as mature endogenous peptides by mass spectrometry from brain samples purified by immunoaffinity chromatography. GnIH mRNA expression was higher in long days (LD) compared with short days (SD). GnIH mRNA was also highly expressed in SD plus pinealectomized animals, whereas expression was suppressed by melatonin, a nocturnal pineal hormone, administration. GnIH-immunoreactive (-ir) neurons were localized to the dorsomedial region of the hypothalamus, and GnIH-ir fibers projected to hypothalamic and limbic structures. The density of GnIH-ir perikarya and fibers were higher in LD and SD plus pinealectomized hamsters than in LD plus melatonin or SD animals. The percentage of GnRH neurons receiving close appositions from GnIH-ir fiber terminals was also higher in LD than SD, and GnIH receptor was expressed in GnRH-ir neurons. Finally, central administration of hamster RFRP-1 or RFRP-3 inhibited LH release 5 and 30 min after administration in LD. In sharp contrast, both peptides stimulated LH release 30 min after administration in SD. These results suggest that GnIH peptides fine tune LH levels via its receptor expressed in GnRH-ir neurons in an opposing fashion across the seasons in Siberian hamsters.

  13. LipL21 mRNA expression in lungs of hamsters infected with pathogenic Leptospira

    Institute of Scientific and Technical Information of China (English)

    Chintana Chirathaworn; Namo Suksomyos; Somchai Utivamek; Somboon Keelawat; Duangjai Suwancharoen; Duangporn Phulsuksombati; Yong Poovorawan

    2009-01-01

    Objective:Pulmonary haemorrhage is an increasing cause of death in leptospirosis patients.However,molecu-lar mechanism underlying pathologies in this organ is not clearly understood.It has been shown that sodium transport was disturbed following Leptospira infection.LipL21 is the second abundant outer membrane protein found only in pathogenic Leptospira.Its expression in vivo has been shown which suggests that this protein may be involved in survival in hosts or pathogenesis.However,the expression of this protein in host organs and its role in lung pathology has not been demonstrated.In this study we demonstrated the expression of LipL21 in lungs of hamsters infected with pathogenic Leptospira.Methods:Lung tissues were collected from Golden Syri-an hamsters injected with Leptospira interrogans serovar Pyrogenes at days 3,5 and 7 post-infection.Four ham-sters were used for each time point.Lungs from non-infected hamsters were collected as a control group.Li-pL21 mRNA expression in lung tissues was investigated by reverse transcription and nested PCR.Results:Li-pL21 mRNA expression was detected in all lung tissues from hamsters infected with pathogenic Leptospira.No PCR product was detected when tissues from non-infected hamsters were investigated.Conclusion:Our data demonstrated that LipL21 is expressed in lungs of hamsters infected with pathogenic Leptospira.Additional ex-periments such as quantitation and localization of LipL21 expression in lungs will provide further information whether this protein is involved in pathogenesis.

  14. Chlorpromazine distribution in hamsters and mice bearing transplantable melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Fairchild, R.G. (Brookhaven National Lab., Upton, NY); Greenberg, D.; Watts, K.P.; Packer, S.; Atkins, H.L.; Som, P.; Hannon, S.J.; Brill, A.B.; Fand, I.; McNally, W.P.

    1982-02-01

    Chlorpromazine (CPZ) distribution was measured in tissues of Syrian golden hamsters bearing Greene melanoma and in BALB/c mice bearing Harding-Passey melanoma. Distribution was evaluated as a function of time (0.5 to 14 days) and as a function of single and multiple doses (up to five) of from 5 to 50 mg CPZ per kg body weight. Routes of administration (i.p., i.v., p.o.) were compared. The physiological behavior of CPZ is of interest as it is used extensively as a tranquilizing drug (Thorazine). Further, since CPZ binds to the pigment melanin, the possibility exists of using CPZ to transport diagnostic or therapeutic agents to melanoma. It was found that, at 2 days postinjection, tumor/tissue concentration ratios exceeded 10 for metabolizing organs, such as liver, and 100 for background tissues, such as blood and muscle. Absolute concentrations of CPZ in tumor exceeding 100 ..mu..g CPZ per g tumor were obtained with both single and multiple doses. This selective high concentration in tumor would make CPZ an ideal vehicle for the transport of boron to tumor for use in neutron capture therapy via the /sup 10/B(n,..cap alpha..)/sup 7/Li reaction.

  15. The dystrophic hamster: an animal model of alveolar hypoventilation.

    Science.gov (United States)

    Schlenker, E H; Burbach, J A

    1991-11-01

    The BIO 14.6 dystrophic hamster (DH) is a genetically determined animal model of alveolar hypoventilation (AH) that exhibits a ventilatory control pattern of compensation and then decompensation similar to that in progressive forms of muscular dystrophy and nonprogressive congenital myopathies in humans. Possible causes of AH in the DH include respiratory muscle weakness, ventilation-to-perfusion inequalities, and an inadequate drive to breathe. Histochemical and contractile abnormalities of the diaphragm, reduced lung surface area available for gas exchange, abnormal pulmonary microvascular reactivity to hypoxia, altered levels of neurochemicals, and abnormal cellular regulation of calcium are among the specific factors that may contribute to the development of AH. The potential role of hypothyroidism in the development of AH is reviewed because many hypothyroid patients exhibit AH and other ventilatory dysfunctions, hypothyroidism is present in human patients and animals with muscular dystrophy, and thyroid status is known to influence lung architecture, myocyte function, and neural activity. Additional studies linking neurohormonal signals, transcellular signal processing, and control of ventilation in the DH may help us understand the etiology of AH in human disease. PMID:1684789

  16. Red Yeast Rice Increases Excretion of Bile Acids in Hamsters

    Institute of Scientific and Technical Information of China (English)

    KA-YING MA; ZE-SHENG ZHANG; SHU-XIN ZHAO; QI CHANG; YIN-MEI WONG; SAI YING VENUS YEUNG; YU HUANG; ZHEN-YU CHEN

    2009-01-01

    Objectives To investigate the hypocholesterolemic activity of red yeast rice (RYR) and its underlying mechanism. Methods Three groups of hamsters were fed either the control diet or one of the two experimental diets containing by weight 0.1% RYR (0.1RYR) or 0.3% RYR (0.3RYR). Blood (0.5 mL) was collected from the retro-orbital sinus into a heparinized capillary tube at the end of week 0,3, and 6.Plasma lipoproteins were measured using enzymatic kits, while fecal neutral and acidic sterols were quantified using a gas-liquid chromatography. Results Plasma total cholesterol was reduced by 12% in 0.1RYR group and by 18% in 0.3RYR group compared with the control value. Similarly, plasma triacylglycerol was decreased by ll% in 0.1RYR group and by 24% in 0.3RYR group. Western blotting analysis demonstrated that RYR had no effect on sterol regulatory element binding protein 2, liver X receptor, 3-hydroxy-3-methylglutary-CoA reductase, LDL receptor, and cholesterol-7α-hydroxylase. HPLC analysis confirmed that RYR contained 0.88% monacolin K.It was recently found that RYR supplementation increased excretion of fecal acidic sterols by 3-4 folds compared with the control value. Conclusion Hypocholesterolemic activity of RYR is mediated at least partially by enhancement of acidic sterol excretion.

  17. Teratogenic effects of mescaline, epinephrine, and norepinephrine in the hamster.

    Science.gov (United States)

    Hirsch, K S; Fritz, H I

    1981-06-01

    Mescaline was administered orally at doses of 16 and 32 mg/kg on the seventh through tenth days of gestation to pregnant cream-strain hamsters. This treatment resulted in a dose-dependent effect on reproductive success and skeletal ossification. The effect of mescaline on reproductive success included an increased number of resorptions resulting in a decreased litter size. The 32 mg/kg dose of mescaline caused 48.8% resorptions, while 16 mg/kg and control animals had 12.0% and 6.4% resorptions, respectively. Litter size was decreased from 12.0 pups in controls to 10.3 (16 mg/kg) and 6.5 (32 mg/kg) pups per litter in treated groups. No gross abnormalities were observed at necropsy; there was, however, a dose-dependent increased delay in the ossification of the skull, sternum, and metatarsals. Both epinephrine and norepinephrine caused a decrease in reproductive success when administered at 500 micrograms/kg. Epinephrine appeared to cause a trend toward preimplantation wastage as indicated by an increased corpora lutea to implantation site ratio (from 1.3-1.9). Norepinephrine, however, caused an increased number of resorptions (29.1% in controls). Both norepinephrine and epinephrine produced similar delays in ossification.

  18. HAMSTER: visualizing microarray experiments as a set of minimum spanning trees

    Directory of Open Access Journals (Sweden)

    Harada Hajime

    2009-11-01

    Full Text Available Abstract Background Visualization tools allow researchers to obtain a global view of the interrelationships between the probes or experiments of a gene expression (e.g. microarray data set. Some existing methods include hierarchical clustering and k-means. In recent years, others have proposed applying minimum spanning trees (MST for microarray clustering. Although MST-based clustering is formally equivalent to the dendrograms produced by hierarchical clustering under certain conditions; visually they can be quite different. Methods HAMSTER (Helpful Abstraction using Minimum Spanning Trees for Expression Relations is an open source system for generating a set of MSTs from the experiments of a microarray data set. While previous works have generated a single MST from a data set for data clustering, we recursively merge experiments and repeat this process to obtain a set of MSTs for data visualization. Depending on the parameters chosen, each tree is analogous to a snapshot of one step of the hierarchical clustering process. We scored and ranked these trees using one of three proposed schemes. HAMSTER is implemented in C++ and makes use of Graphviz for laying out each MST. Results We report on the running time of HAMSTER and demonstrate using data sets from the NCBI Gene Expression Omnibus (GEO that the images created by HAMSTER offer insights that differ from the dendrograms of hierarchical clustering. In addition to the C++ program which is available as open source, we also provided a web-based version (HAMSTER+ which allows users to apply our system through a web browser without any computer programming knowledge. Conclusion Researchers may find it helpful to include HAMSTER in their microarray analysis workflow as it can offer insights that differ from hierarchical clustering. We believe that HAMSTER would be useful for certain types of gradient data sets (e.g time-series data and data that indicate relationships between cells/tissues. Both

  19. Dim nocturnal illumination alters coupling of circadian pacemakers in Siberian hamsters, Phodopus sungorus.

    Science.gov (United States)

    Gorman, M R; Elliott, J A

    2004-08-01

    The circadian pacemaker of mammals comprises multiple oscillators that may adopt different phase relationships to determine properties of the coupled system. The effect of nocturnal illumination comparable to dim moonlight was assessed in male Siberian hamsters exposed to two re-entrainment paradigms believed to require changes in the phase relationship of underlying component oscillators. In experiment 1, hamsters were exposed to a 24-h light-dark-light-dark cycle previously shown to split circadian rhythms into two components such that activity is divided between the two daily dark periods. Hamsters exposed to dim illumination (rhythms compared to hamsters exposed to completely dark scotophases. In experiment 2, hamsters were transferred to winter photoperiods (10 h light, 14 h dark) from two different longer daylengths (14 h or 18 h light daily) in the presence or absence of dim nighttime lighting. Dim nocturnal illumination markedly accelerated adoption of the winter phenotype as reflected in the expansion of activity duration, gonadal regression and weight loss. The two experiments demonstrate substantial efficacy of light intensities generally viewed as below the threshold of circadian systems. Light may act on oscillator coupling through rod-dependent mechanisms.

  20. The Influence of Red Wine on Lipid of Golden Hamsters Plasma

    Institute of Scientific and Technical Information of China (English)

    GUO Jin-ying; LI Hua; WANG Hua; YUAN Chun-long; XIE Ren-ming

    2007-01-01

    This experiment was conducted on 50 male golden hamsters, which were divided into five groups. Each group contained 10 hamsters: red wine group, alcohol-free red wine group, alcohol group, hyperlipidemia group, and control group. During the four-week regime, all the hamsters were fed with a high cholesterol diet, except the control group. After completion of the trial, the plasma lipid levels and lipid peroxidation contents were determined in the golden hamsters, and the morphological variation in liver cells was investigated with electron microscopy. The results showed that concentrations of TC and TG in red wine, alcohol-free red wine, and alcohol groups had decreased dramatically. Compared with the hyperlipidemia group, the levels of LDL-C had significantly decreased in other groups, but not the HDL-C. Consumption of red wine,alcohol-free red wine, and alcohol, had no significant effects on Apo A1 and Apo B. Red wine, alcohol-free red wine, and alcohol significantly decreased the contents of MDA in hamsters. The experiment demonstrated that red wine could ameliorate the incidence of atherosclerosis (AS) via reducing serum TC, TG, LDL-C, and the compounds in red wine had synergic effects.