Decorporation of 241Am and 252Cf by Ca-DTPA from rat, Syrian and Chinese hamster

International Nuclear Information System (INIS)

Seidel, A.

1977-01-01

Retention and mobilization by Ca-DTPA of 241 Am and 252 Cf from rats, Syrian and Chinese hamsters are compared. Previous observations of a much longer residence time of actinides in hamsters liver than in rat liver are confirmed. Identical dose-effect functions were obtained for skeleton of rats and Syrian hamsters whereas 252 Cf removal from Chinese hamster skeleton was lower. The mobilization of 241 Am was lower than that of 252 Cf. With regard to species differences, qualitatively similar results were obtained for 241 Am as for 252 Cf. The results will be discussed with regard to the reduction by DTPA treatment of radiation risk in animal species with different biological half times of actinides in their livers. In this connection, attention will be paid to the usefulness of long-term DTPA treatment

cDNA cloning and nucleotide sequence comparison of Chinese hamster metallothionein I and II mRNAs

Energy Technology Data Exchange (ETDEWEB)

Griffith, B B; Walters, R A; Enger, M D; Hildebrand, C E; Griffith, J K

1983-01-01

Polyadenylated RNA was extracted from a cadmium resistant Chinese hamster (CHO) cell line, enriched for metal-induced, abundant RNA sequences and cloned as double-stranded cDNA in the plasmid pBR322. Two cDNA clones, pCHMT1 and pCHMT2, encoding two Chinese hamster isometallothioneins were identified, and the nucleotide sequence of each insert was determined. The two Chinese hamster metallothioneins show nucleotide sequence homologies of 80% in the protein coding region and approximately 35% in both the 5' and 3' untranslated regions. Interestingly, an 8 nucleotide sequence (TGTAAATA) has been conserved in sequence and position in the 3' untranslated regions of each metallothionein mRNA sequenced thus far. Estimated nucleotide substitution rates derived from interspecies comparisons were used to calculate a metallothionein gene duplication time of 45 to 120 million years ago. 39 references, 1 figure, 1 table.

Influence of 239Pu aerosol production temperature on biological responses in Chinese hamsters

International Nuclear Information System (INIS)

Brooks, A. L.; Peters, R.F.; Mewhinney, J.A.

1977-01-01

Studies on the retention, distribution and effects of inhaled 239 Pu particles produced at different temperatures are continuing in an effort to assess the consequences of accidental inhalation exposures under various conditions. Three groups of Chinese hamsters, 381 animals per group, were exposed to aerosols of 239 Pu which had been treated in a heating column at either 50, 600 or 1150 0 C. Retention and distribution of the plutonium through 600 days after exposure reflected the relative insolubility of the aerosols heated at 1150 and 600 0 C, and the relative solubility of the aerosol heated at 50 0 C. Animals exposed to either of the insoluble aerosols had 80 to 90 percent of the sacrifice body burden in the lung at 400 days after exposure whereas animals exposed to the aerosol heated at 50 0 C had only 10 percent of the sacrifice body burden in the lung at 400 days. Translocation was mainly to the liver. To date, survival of the animals seemed to depend primarily on activity level, with production temperature exerting an influence only at the highest activities

A Consensus Genome-scale Reconstruction of Chinese Hamster Ovary Cell Metabolism

DEFF Research Database (Denmark)

Hefzi, Hooman; Ang, Kok Siong; Hanscho, Michael

2016-01-01

Chinese hamster ovary (CHO) cells dominate biotherapeutic protein production and are widely used in mammalian cell line engineering research. To elucidate metabolic bottlenecks in protein production and to guide cell engineering and bioprocess optimization, we reconstructed the metabolic pathways...

The effect of dietary vitamin A on NO2 exposure on the hamster lung

International Nuclear Information System (INIS)

Kim, J.C.

1978-01-01

The effect of dietary vitamin A and NO2 exposure on the hamster lung was evaluated by histopathology, electron microscopy, and thymidine uptake studies. Hamsters were maintained on deficient (0 micrograms), adequate (100 micrograms), and high (200 micrograms) dose levels of vitamin A while being exposed repeatedly to 10 ppm of NO2 for 5 hours once a week over an 8-week period. Hamsters of the deficient group exhibited clinical and morphologic changes characteristic of vitamin A deficiency. Animals maintained on adequate and high dose levels of vitamin A were not affected by vitamin A deficiency. Hypertrophy and hyperplasia of the epithelial cells of the terminal bronchiolar alveolar region of lungs of adequately and highly dosed animals were greater than those observed in the deficient animals, when NO2 exposure was given. However, the extent of the lesions observed in all three groups was less than that seen in normal hamsters given a single, 5-hour NO2 exposure. Ultrastructural changes observed in vitamin A-deficient hamsters exposed to NO2 were hypertrophy and hyperplasia of bronchiolar epithelial cells, diffuse loss of cilia, membrane damage, and mitochondrial damage manifested by calcium deposition. Tritiated thymidine uptake studies of lungs of animals exposed repeatedly revealed a rather erratic cell renewal pattern following NO2 exposure in comparison to the group of animals exposed singly

Model-based analysis of N-glycosylation in Chinese hamster ovary cells

DEFF Research Database (Denmark)

Krambeck, Frederick J.; Bennun, Sandra V; Andersen, Mikael Rørdam

2017-01-01

The Chinese hamster ovary (CHO) cell is the gold standard for manufacturing of glycosylated recombinant proteins for production of biotherapeutics. The similarity of its glycosylation patterns to the human versions enable the products of this cell line favorable pharmacokinetic properties and lower...

Multistep change in epidermal growth factor receptors during spontaneous neoplastic progression in Chinese hamster embryo fibroblasts

International Nuclear Information System (INIS)

Wakshull, E.; Kraemer, P.M.; Wharton, W.

1985-01-01

Whole Chinese hamster embryo lineages have been shown to undergo multistep spontaneous neoplastic progression during serial passage in culture. The authors have studied the binding, internalization, and degradation of 125 I-labeled epidermal growth factor at four different stages of transformation. The whole Chinese hamster embryo cells lost cell surface epidermal growth factor receptors gradually during the course of neoplastic progression until only 10% of the receptor number present in the early-passage cells (precrisis) were retained in the late-passage cells (tumorigenic). No differences in internalization rates, chloroquine sensitivity, or ability to degrade hormone between the various passage levels were seen. No evidence for the presence in conditioned medium of transforming growth factors which might mask or down-regulate epidermal growth factor receptor was obtained. These results suggest that a reduction in cell surface epidermal growth factor receptor might be an early event during spontaneous transformation in whole Chinese hamster embryo cells

Lung lecithin synthesis in Syrian hamster lung: effect of pulmonary lavage

International Nuclear Information System (INIS)

Henderson, R.F.

1976-01-01

A single pulmonary lavage in the Syrian hamster stimulated the synthesis of both the surface-active dipalmitoyl lecithin and its proposed precursor, the unsaturated lecithins. The rate of breakdown of the two types of lung lecithin did not appear to be greatly affected by the lavage. The data were consistent with the view that alveolar lecithins are secreted by the tissue into the alveoli and that unsaturated lecithins are the precursors of dipalmitoyl lecithin

Spontaneous mutation rate in Chinese hamster cell clones differing in UV-sensitivity

International Nuclear Information System (INIS)

Manuilova, E.S.; Bagrova, A.M.; Moskovskij Gosudarstvennyj Univ.

1983-01-01

The spontaneous rate of appearance of mutations to 6-mercaptopurine (6 MP) resistence in the cells of CHR2 and CHs2 clones dofferent in sensitivity to lethal and matagenous effect of UV-rays, is investigated. Increased UV-sensitivity of CHs2 clone is caused by the violation of postreplicative DNA reparation. It is established that the purity of spontaneously occuring mutations in both clones turns out to be similar, i.e. (1.5-1.8)x10 -5 for the cell pergeneration. It is shown that the effect of postreplicative DNA reparation in the cells of chinese hamster is not connected with the increase of spontaneous mutation ability. The problem on the possible role of reparation in the mechanism of appearance of spontaneous and induced mutations in the cells of Chinese hamster with increased UV-sensitivity is discussed

Biological effect of focal alpha radiation on the hamster lung

International Nuclear Information System (INIS)

Smith, D.M.; Anderson, E.C.; Prine, J.R.; Holland, L.M.; Richmond, C.R.

1975-11-01

Monodispersed 10-μm diameter ZrO 2 ceramic microspheres, containing varying amounts of 239 PuO 2 or 238 PuO 2 , were injected into the jugular vein of 100-day-old Syrian hamsters. These biologically inert microspheres lodged subsequently in pulmonary capillaries and remained static in position throughout the life span of the animals with no discernible inflammatory response. The numbers of microspheres injected ranged from 2000 to 10,000 and the specific activity from 0 to 59 pCi/sphere so that the lung burdens were 0 to 354 nCi/animal. At these numbers, each plutonium-laden microsphere served as an independent, focal source of alpha radiation. No consistent alteration of life spans post-exposure was seen in the experimental hamsters compared to controls. Pulmonary tissue responses were minimal with only 0.5 percent of the animals given Pu/ZrO 2 microspheres ultimately developing primary tumors of the lung. No unexpected gross or histologic lesion were found in other major body tissues

Chinese hamster ovary cell lysosomes retain pinocytized horseradish peroxidase and in situ-radioiodinated proteins

International Nuclear Information System (INIS)

Storrie, B.; Sachdeva, M.; Viers, V.S.

1984-01-01

We used Chinese hamster ovary cells, a cell line of fibroblastic origin, to investigate whether lysosomes are an exocytic compartment. To label lysosomal contents, Chinese hamster ovary cells were incubated with the solute marker horseradish peroxidase. After an 18-h uptake period, horseradish peroxidase was found in lysosomes by cell fractionation in Percoll gradients and by electron microscope cytochemistry. Over a 24-h period, lysosomal horseradish peroxidase was quantitatively retained by Chinese hamster ovary cells and inactivated with a t 1/2 of 6 to 8 h. Lysosomes were radioiodinated in situ by soluble lactoperoxidase internalized over an 18-h uptake period. About 70% of the radioiodine incorporation was pelleted at 100,000 X g under conditions in which greater than 80% of the lysosomal marker enzyme beta-hexosaminidase was released into the supernatant. By one-dimensional electrophoresis, about 18 protein species were present in the lysosomal membrane fraction, with radioiodine incorporation being most pronounced into species of 70,000 to 75,000 daltons. After a 30-min or 2-h chase at 37 degrees C, radioiodine that was incorporated into lysosomal membranes and contents was retained in lysosomes. These observations indicate that lysosomes labeled by fluid-phase pinocytosis are a terminal component of endocytic pathways in fibroblasts

The effect of cigarette smoke on the metabolism of arachidonic acid in isolated hamster lungs

International Nuclear Information System (INIS)

Maennistoe, J.; Toivonen, H.; Hartiala, J.; Bakhle, Y.S.; Uotila, P.

1981-01-01

The effects of cigarette smoke on the metabolism of exogenous arachidonic acid (AA) were investigated in isolated hamster lungs. Arachidonate was injected into the pulmonary circulation and the metabolites were analysed from the nonrecirculating perfusion effluent by thin layer chromatography. After the pulmonary injection of 66 nmol of 14C-AA about 20% of the injected radioactivity appeared in the perfusion effluent mostly as metabolites in six minutes. When isolated lungs were ventilated with cigarette smoke during the perfusion, the amounts of PGF2 alpha, PGE2 and two unidentified metabolite groups increased in the lung effluent. In two other experimental series hamsters were exposed to cigarette smoke before the lung perfusion either once for 30 min or during one hour daily for ten consecutive days. Neither pre-exposures caused any changes in the amounts of arachidonate metabolites in the lung effluent

Radioprotective effect of catecholamines on the cultured Chinese hamster fibroblasts

International Nuclear Information System (INIS)

Chirkov, Yu.Yu.; Malatsidze, M.A.; Sobolev, A.S.

1985-01-01

On cultivated in vitro Chinese hamster fibroblasts radioprotective properties of adrenaline, noradrenaline and isoproterenol in different concentrations are studied. Isoproterenol radiopreventive effect is clearly manifested with its concentration being 1x10 -8 M; adrenaline and noradrenaline are efficient in higher concentrations. Propranolol, blocking β-adrenergic receptors, completely presents radioprotective effect of catecholamines on the cells. β-adrenergic mechanism of catecholamine radioprotective effect on Mammalia cells is discussed

Inhibition of DNA replication by ozone in Chinese Hamster V79 cells

International Nuclear Information System (INIS)

Rasmussen, R.E.

1986-01-01

DNA replication in Chinese hamster lung fibroblasts, line V79, was depressed in a dose-dependent manner over an ozone concentration range of 1-10 ppm. When the cells were exposed for 1 h at concentrations up to 6 ppm, the rate of DNA replication, as measured by [ 3 H]thymidine incorporation, declined further during a 3-h period immediately following exposure. At higher ozone concentrations, at which more than 99.9% of the cells were killed, no further decline in DNA replication was seen beyond that immediately following exposure. Cultures exposed for 1 h to 10 mM ethyl methanesulfonate or to 10 J/m 2 of ultraviolet (UV) light showed a similar progressive decline in the rate of DNA replication. The inhibition of DNA replication by ozone resembled that seen after exposure of cells to chemical mutagens or radiation and did not resemble the inhibition produced by metabolic poisons. The results may indicate that ozone or its reaction products interact directly with DNA in a way that inhibits replication

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...

Spermatogonial multiplication in the Chinese hamster. II. Cell cycle properties of undifferentiated spermatogonia

NARCIS (Netherlands)

Lok, D.; Jansen, M. T.; de rooij, D. G.

1983-01-01

The cell cycle properties of undifferentiated spermatogonia in the Chinese hamster were analysed by the fraction of labelled mitoses technique (FLM) in whole mounted seminiferous tubules. The minimum cell cycle time (Tc) was found to be c. 90 hr for the As and 87 hr for the Apr and Aal

Dicholesteroyl diselenide: cytotoxicity, genotoxicity and mutagenicity in the yeast Saccharomyces cerevisiae and in Chinese hamster lung fibroblasts.

Science.gov (United States)

de Oliveira, Iuri Marques; Degrandi, Tiago Hoerbe; Jorge, Patrícia Mendes; Saffi, Jenifer; Rosa, Renato Moreira; Guecheva, Temenouga Nikolova; Henriques, João Antonio Pêgas

2014-03-15

The organoselenium compound, dicholesteroyl diselenide (DCDS) is a structural analogue of diphenyl diselenide (DPDS) and may be considered as a promising antioxidant drug in vivo. Nevertheless, little is known about the toxicological properties of DCDS. In the present study we evaluated the cytotoxic, genotoxic and mutagenic properties of DCDS in Chinese hamster lung fibroblasts (V79) and in strains of the yeast Saccharomyces cerevisiae, proficient and deficient in several DNA-repair pathways. The results with V79 cells show that DCDS induced cytotoxicity, GSH depletion and elevation of lipid peroxidation at lower concentrations than did DPDS. DCDS also generated single- and double-strand DNA breaks in V79 cells, both in the presence and in the absence of metabolic activation, as revealed by alkaline and neutral comet assays. Moreover, the induction of oxidative DNA base-damage was demonstrated by means of a modified comet assay with formamidopyrimidine-DNA glycosylase and endonuclease III. Treatment with DCDS also induced micronucleus formation in V79 cells as well as point and frame-shift mutations in a haploid wild-type strain of S. cerevisiae. Yeast mutants defective in base excision-repair proteins were the most sensitive to DCDS. Pre-incubation with N-acetylcysteine reduced DCDS's oxidative, genotoxic and mutagenic effects in yeast and in V79 cells. Our findings indicate that the presence of cholesteroyl substituents in DCDS results in elevation of its cytotoxic and genotoxic potential compared with that of DPDS in yeast and in V79 cells. However, due to dose-dependent contrasting behaviour of organoselenium compounds and differences in their toxicity in in vitro and in vivo systems, further studies are needed in order to establish the non-toxic concentration range for treatment in mammals. Copyright © 2014 Elsevier B.V. All rights reserved.

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...

Association of 239Pu with lysosomes in rat, Syrian hamster, and Chinese hamster liver as studied by carrier-free electrophoresis and electron microscopic autoradiography with 241Pu

International Nuclear Information System (INIS)

Seidel, A.; Krueger, E.W.; Wiener, M.; Hotz, G.; Balani, M.; Thies, W.G.

1985-01-01

The binding of injected monomeric plutonium in the liver of rats, Syrian hamsters, and Chinese hamsters (species which show profound differences in their ability to eliminate 239 Pu from the liver) was investigated by carrier-free electrophoresis using 239 Pu and electron microscopic autoradiography with 241 Pu. These studies are part of a program designed to obtain a better understanding of the mechanisms of the clearance of transuranium elements from liver of different mammals and man. Between 4 and 9 days after nuclide injection, a clear correlation between the majority of the 239 Pu and lysosomal enzymes was observed when the mitochondrial-lysosomal (ML) fraction of the livers was analyzed by carrier-free electrophoresis. In the two hamster species, a second 239 Pu peak exists from the beginning and increases with time to comprise 50% of the total radioactivity at later times. During electron microscopic examination 4 days after 241 Pu injection, beta tracks were frequently observed over globular structures resembling dense bodies in Chinese hamster liver. They were also observed frequently over chromatin-rich portions of the cell nuclei. These results, together with those from previous density gradient studies, show that lysosomes are the primary deposition site for 239 Pu in the liver cytoplasm of these three rodent species. The hypothesis of a morphologic transformation of these lysosomes with time in hamster liver and of rapid bulk exocytosis of the lysosomes in rats are still possible explanations for the extreme differences in the elimination among the three species

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

International Nuclear Information System (INIS)

Bryant, R.E.; Schauer, I.E.; Hatcher, D.G.

1981-01-01

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 ( 3 H) hypoxanthine for 5 or 10 min, followed by storage of 3 H-labelled cells at -70 0 C for 4-10 days. 12 clones that survived the 3rd kill cycle were tested for incorporation of ( 3 H)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.)

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

Chinese hamster ovary (CHO) cells, first isolated in 1957, are the preferred production host for many therapeutic proteins. Although genetic heterogeneity among CHO cell lines has been well documented, a systematic, nucleotide-resolution characterization of their genotypic differences has been st...

Intracellular pH in increased after transformation of Chinese hamster embryo fibroblasts

International Nuclear Information System (INIS)

Ober, S.S.; Pardee, A.B.

1987-01-01

These studies reveal that a series of tumorigenic Chinese hamster embryo fibroblast (CHEF) cell lines maintain an internal pH (pH/sub i/) that is 0.12 +/- 0.04 pH unit above that of the nontumorigenic CHEF/18 parental line. pH measurements were made with [ 14 C]-benzoic acid. This increase of pH/sub i/ in the tumorigenic CHEF cells is not due to autocrine growth factor production or to the persistent activation of pathways previously shown to modulate Na + /H + -antiporter activity present in the CHEF/18 line. These findings suggest that the defect in pH/sub i/ regulation in the tumorigenic CHEF/18 derivatives lies in the Na + /H + antiporter itself. Further studies to determine the biological significance of an increased pH/sub i/ show that the external pH (pH 0 )-dependence curve for initiation of DNA synthesis in the tumorigenic CHEF lines is shifted by approximately 0.2 pH unit toward acidic values relative to that of the nontumorigenic CHEF/18 parent. These data show a critical role for pH/sub i/ in the regulation of DNA synthesis in Chinese hamster embryo fibroblasts and demonstrate that aberrations in pH/sub i/ can contribute to the acquisition of altered growth properties

Effects of harman and norharman on spontaneous and ultraviolet light-induced mutagenesis in cultured Chinese hamster cells

International Nuclear Information System (INIS)

Chang, C.C.; Castellazzi, M.; Glover, T.W.; Trosko, J.E.

1978-01-01

Nontoxic concentrations of harman and norharman were tested in cultured Chinese hamster cells for their effects on DNA repair and mutagenesis. The following effects of harman were observed: (a) the survival of ultraviolet light- or x-ray-damaged cells was reduced; (b) the ultraviolet light-induced unscheduled DNA synthesis was slightly inhibited; and (c) the frequency of spontaneous or ultraviolet light-induced ouabain-resistant (ouar) or 6-thioguanine-resistant (6-TGr) mutations was reduced. Furthermore, the effect of harman on survival and mutagenesis was greater than that of norharman and was detected primarily in treatments in which cells were exposed to harman immediately following ultraviolet light irradiation. Our data clearly indicate that harman decreases the capacity to repair DNA damage and fix mutations in Chinese hamster cells, possibly because of the intercalation properties of this compound

Cell killing and mutation induction on Chinese hamster cells by photoradiations

International Nuclear Information System (INIS)

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

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.

Interspecies complementation analysis of xeroderma pigmentosum and UV-sensitive Chinese hamster cells

International Nuclear Information System (INIS)

Stefanini, M.; Keijzer, W.; Westerveld, A.; Bootsma, D.

1985-01-01

Complementation analysis was performed 24 h after fusion of UV-sensitive CHO cells (CHO 12 RO) with XP cells of complementation groups A, B, C, D, F and G. The parental cells are characterized by low levels of unscheduled DNA synthesis (UDS). In all combinations, the UDS levels observed in heterokaryons were higher than those in parental mutant cells, clearly indicating cooperation of human and Chinese hamster repair functions. In heterokaryons of CHO 12 RO with XP-A and XP-C cells, the UDS values reached about the normal human level, whereas in heterokaryons with XP-B, XP-D and XP-F, UDS was restored at a level approaching that in wild-type CHO cells. The results obtained after fusion of CHO cells with two representative cell strains from the XP-G group, XP 2 BI and XP 3 BR, were inconsistent. Fusion with XP 3 BR cells yielded UDS levels ranging from wild-type Chinese hamster to normal human, whereas fusion with XP 2 BI cells resulted in a slight increase in UDS which even after 48 h remained below the level found in wild-type CHO cells. The occurrence of complementation in these interspecies heterokaryons indicates that the genetic defect in the CHO 12 RO cells is different from the defects in the XP complementation groups tested

Efficient procedure for transferring specific human genes into Chinese hamster cell mutants: interspecific transfer of the human genes encoding leucyl- and asparaginyl-tRNA synthetases

International Nuclear Information System (INIS)

Cirullo, R.E.; Dana, S.; Wasmuth, J.J.

1983-01-01

A simple and efficient procedure for transferring specific human genes into mutant Chinese hamster ovary cell recipients has been developed that does not rely on using calcium phosphate-precipitated high-molecular-weight DNA. Interspecific cell hybrids between human leukocytes and temperature-sensitive Chinese hamster cell mutants with either a thermolabile leucyl-tRNA synthetase or a thermolabile asparaginyl-tRNA synthetase were used as the starting material in these experiments. These hybrids contain only one or a few human chromosomes and require expression of the appropriate human aminoacyl-tRNA synthetase gene to grow at 39 degrees C. Hybrids were exposed to very high doses of gamma-irradiation to extensively fragment the chromosomes and re-fused immediately to the original temperature-sensitive Chinese hamster mutant, and secondary hybrids were isolated at 39 degrees C. Secondary hybrids, which had retained small fragments of the human genome containing the selected gene, were subjected to another round of irradiation, refusion, and selection at 39 degrees C to reduce the amount of human DNA even further. Using this procedure, Chinese hamster cell lines have been constructed that express the human genes encoding either asparaginyl- or leucyl-tRNA synthetase, yet less than 0.1% of their DNA is derived from the human genome, as quantitated by a sensitive dot-blot nucleic acid hybridization procedure

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

International Nuclear Information System (INIS)

Drillien, R.; Spehner, D.; Kirn, A.

1978-01-01

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

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

International Nuclear Information System (INIS)

Schroy, C.B.; Todd, P.

1979-01-01

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

Modification of potentially lethal damage in irradiated Chinese hamster V79 cells after incorporation of halogenated pyrimidines

NARCIS (Netherlands)

Franken, N. A.; van Bree, C. V.; Kipp, J. B.; Barendsen, G. W.

1997-01-01

Radiosensitization of exponentially growing and plateau phase Chinese hamster V79 cells by incorporation of halogenated pyrimidines (HP) was investigated for different culture conditions that influenced repair. For this purpose cells were grown for 72 h with 0, 1, 2 and 4 microM of chloro-(CldUrd),

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...

Transfer of human genes conferring resistance to methylating mutagens, but not to UV irradiation and cross-linking agents, into Chinese hamster ovary cells

International Nuclear Information System (INIS)

Kaina, B.; Van Zeeland, A.A.; Backendorf, C.; Thielmann, H.W.; Van de Putte, P.

1987-01-01

Chinese hamster ovary cells were transfected by human DNA ligated to the bacterial gpt (xanthine-guanine-phosphoribosyltransferase) gene which was used either in its native form or after partial inactivation with methylnitrosourea. The gpt+ transfectants were screened for resistance to high doses of N-methyl-N'-nitro-N-nitrosoguanidine. Using this approach, we showed that Chinese hamster ovary cells can acquire N-methyl-N'-nitro-N-nitrosoguanidine resistance upon transfection with DNA from diploid human fibroblasts, that this resistance is transferable by secondary transfection and is specific for methylating mutagens, and that it is not caused by increased removal of O6-methylguanine, 3-methyladenine, and 7-methylguanine from DNA

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...

Postreplication gap filling in the DNA of X-ray-damaged Chinese hamster cells

International Nuclear Information System (INIS)

Koerner, I.; Malz, W.

1975-01-01

In X-irradiated Chinese hamster cells the newly synthesized DNA has a lower molecular weight than the DNA in control cells. This reduced molecular weight has been interpreted by gap induction opposite the lesions in the parental DNA strands. Within two hours these postreplication gaps were closed. With the aid of BrdUrd-photolys-technique it could be demonstrated that the gaps were filled by de novo synthesis. But we were not able to show a participation of parental DNA in the gap-filling process

Mitotic spindle proteomics in Chinese hamster ovary cells.

Directory of Open Access Journals (Sweden)

Mary Kate Bonner

Full Text Available Mitosis is a fundamental process in the development of all organisms. The mitotic spindle guides the cell through mitosis as it mediates the segregation of chromosomes, the orientation of the cleavage furrow, and the progression of cell division. Birth defects and tissue-specific cancers often result from abnormalities in mitotic events. Here, we report a proteomic study of the mitotic spindle from Chinese Hamster Ovary (CHO cells. Four different isolations of metaphase spindles were subjected to Multi-dimensional Protein Identification Technology (MudPIT analysis and tandem mass spectrometry. We identified 1155 proteins and used Gene Ontology (GO analysis to categorize proteins into cellular component groups. We then compared our data to the previously published CHO midbody proteome and identified proteins that are unique to the CHO spindle. Our data represent the first mitotic spindle proteome in CHO cells, which augments the list of mitotic spindle components from mammalian cells.

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...

Suppression of radiation mutagenesis by dactinomycin in Chinese hamster cells

International Nuclear Information System (INIS)

Tokita, N.; Capenter, S.G.; Chen, D.J.; MacInnes, M.A.; Raju, M.R.

1985-01-01

Dactinomycin (AMD) suppression of radiation mutagenesis was investigated using an in vitro mutation assay (6-thioguanine resistance) in Chinese hamster ovary cells. Cells were exposed to acute single doses of x rays followed by 1 hr-treatment with 0.1 or 1 μg/ml AMD. The cell survival curves plotted as a function of x-ray doses were similar for radiation alone and radiation plus AMD. The results suggest that AMD treatment was only slightly mutagenic, however, when given immediately after irradiation, it suppressed radiatiion mutagenesis at higher x-ray dose regions (below 10% survival levels). Higher AMD concentrations appeared more suppressive than lower concentrations. Dose-response data analyzed based on Poisson distribution models suggest the stochastic dependence of x-ray mutagenesis and AMD cytotoxity

The effect of hydroxyurea on synchronized Chinese hamster ovary cells irradiated by ultraviolet light

International Nuclear Information System (INIS)

Burg, K.; Collins, A.R.S.; Johnson, R.T.

1979-01-01

The effect of hydroxyurea (HU) on cell survival was investigated in Chinese hamster ovary cells after different radiation doses of UV light (254 nm) during the individual phases of the cell cycle. HU inhibits the repair DNA replication by mediation through the DNA precursor pool. These results are supported by the absence of the effect of HU both in the G2 phase possessing high levels of precursors and in supplying the 4 deoxyribonucleosides together with HU after irradiation

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

International Nuclear Information System (INIS)

Thompson, L.H.; Salazar, E.P.; Brookman, K.W.; Collins, C.C.; Stewart, S.A.; Busch, D.B.; Weber, C.A.

1986-01-01

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

Modification of UV-induced mutation frequencies in Chinese hamster- cells by dose fractionation, cycloheximide and caffeine treatments

International Nuclear Information System (INIS)

Chang, C.-C.; Schultz, R.; Trosko, J.E.; D'Ambrosio, S.M.; Setlow, R.B.

1978-01-01

Chinese hamster (V79) cells were irradiated with a fractionated regime of ultraviolet light (UV 1 +UV 2 ). The fractionation of a UV dose always increased the colony-forming ability but reduced (or it did not change) the mutation frequencies. Treatment with cycloheximide between the two UV irradiations resulted in two types of effects, depending on the protocols used. Long exposures to cycloheximide (i.e., >6h) for the entire period between UV 1 and UV 2 or partial treatment of cycloheximide (i.e., 3h) long before UV 2 always resulted in reduced colony-forming ability and enhanced or unchanged mutation frequencies. Exposure to cycloheximide for the entire period in the short fractionated regime (i.e., 4h) between UV 1 and UV 2 or partial treatment of cycloheximide just prior to UV 2 tended to give the opposite effects. Caffeine treatment before UV 2 , with or without UV 1 , significantly increased the mutation frequencies. These results suggest that an error-free postreplication repair system exists in Chinese hamster cells which is inhibitable by particular cycloheximide or caffeine treatments. (Auth.)

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

International Nuclear Information System (INIS)

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

2006-01-01

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

Uptake of low density lipoproteins by the hamster lung. Interactions with capillary endothelium

International Nuclear Information System (INIS)

Nistor, A.; Simionescu, M.

1986-01-01

The mechanism by which the circulating low density lipoproteins (LDL) contribute to the lung surfactant cholesterol was investigated by perfusing the hamster lung in situ with LDL either radiolabeled or coupled to gold, or both. Part of [ 125 I]-LDL and [ 3 H]-cholesterol LDL were taken up by a specific process which was time- and concentration-dependent and reached saturation within 20 to 30 min of perfusion. Competition experiments and removal of receptor-bound LDL by heparin suggested that about 50% of LDL uptake is receptor-independent. Experiments using double labeled LDL showed a preferential uptake of 3 H-cholesterol versus 125 I by the lung both in situ and in vivo. LDL-gold particles (LDL-Au), recirculated through the isolated lung, bound to the endothelial luminal plasma membrane and to features potentially involved in receptor-mediated endocytosis (coated pits, coated vesicles, lysosomelike structures) and in transcytosis (plasmalemmal vesicles). The results suggest that LDL uptake by the lung takes place by both receptor-mediated and receptor-independent mechanisms. Cholesterol may be in part transferred to the lung without the apoprotein moiety; the alveolar capillary endothelium appears to be the first monitor of this complex process

12-O-Tetradecanoyl-phorbol-13-acetate and its relationship to SCE induction in Syrian and Chinese hamster cells

International Nuclear Information System (INIS)

Popescu, N.C.; Amsbaugh, S.C.; Larramendy, M.L.; DiPaolo

1982-01-01

12-O-Tetradecanoyl-phorbol-13-acetate (TPA) in conditions that produce enhancement of ultraviolet light (UV) and x-irradiation Syrian hamster embryo cell (HEC) transformation did not cause further increase in the sister chromatid exchange (SCE) frequency induced by UV and x-irradiation, two physical carcinogens that differ in their mode of DNA interaction and efficiency of SCE induction. Several factors which might influence SCE induction by TPA were studied on HEC and Chinese hamster V79-4 cells. Heat-inactivated serum was used because of the possibility that a serum component may interfere with TPA ability to cause SCE. TPA effect on SCE was determined at the first and second division post treatment on cells exposed to different 5-bromodeoxyuridine (BrdUrd) concentrations. Independent of BrdUrd concentration (1-10μg/ml medium) and the number of cells divisions post treatment, TPA (0.01-2μg/ml medium) was ineffective in inducing SCE in exponentially and stationary HEC cultures cultivated in medium supplemented with heat-inactivated serum. Also, TPA did not increase the SCE frequency in V79-4 Chinese hamster cells cultured in heat-activated or noninactivated serum. Although SCE induction, a cellular response to carcinogen-induced DNA damage, may be important for the induction of transformation by environmental agents, the enhancement of transformation frequency caused by TPA occurs without further DNA alterations involved in SCE formation

Neonatal oocyte development and selective oocyte-killing by X-rays in the Chinese hamster, Cricetulus griseus

Energy Technology Data Exchange (ETDEWEB)

Tateno, H.; Mikamo, K. (Asahikawa Medical Coll. (Japan). Dept. of Biological Sciences)

1984-02-01

The process of ovarian development in neonatal Chinese hamsters aged between 0 and 16 days was studied histologically and quantitatively in both a non-irradiated group and an irradiated group. In the latter, ovaries were exposed to a single dose of 1 Gy X-rays on days 0, 2, 4, 6, 8, 10, 12 and 14 after birth. All oocytes on day 0 were at pachytene, and nearly all of them seemed to develop to dictyate by day 10. A quantitative analysis of age-dependent changes in the distribution of oocytes showed that a marked spontaneous degeneration of oocytes took place twice, i.e. during pachytene (day 0 to day 4) and dictyate (day 12 to day 14). Oocytes of this species were found to be very radioresistant at pachytene, but to become sharply sensitive during the phases between diplotene and early dictyate, suffering an almost complete oocyte-killing after 1 Gy. However, they recovered radioresistance after the onset of the resting stage. The changing aspects of radiosensitivity in the Chinese hamster were shown to be far more marked than in the mouse and the rat, which have been observed by previous investigators.

Isolation and characterization of variant clones of Chinese hamster cells after treatment with irradiated 5-iodouridine

International Nuclear Information System (INIS)

Kuroda, Y.; Yokoiyama, A.; Kada, T.

1975-01-01

Variant clones were isolated from cultured Chinese hamster Don cells after treatment with irradiated 5-iodouridine. The following characters of a primary variant clone, C-11 and a secondary variant clone, C-24 were compared with those of the original clone C-1: colony-forming activity, growth rate in the presence of irradiated and unirradiated 5-iodouridine, distribution of chromosome numbers and cell cohesion. The variant clones C-11 and C-24 were partially resistant to unirradiated 5-iodouridine at lower concentration and C-24 cells were slightly resistant to short-term treatment with irradiated 5-iodouridine. Unlike clones C-1 and C-11, the variant clone C-24 showed no lag phase on growth in 5-iodouridine medium. The modal numbers of the chromosomes of all three clones were 22, like that of normal Chinese hamster diploid cells. Of the three clones, the variant C-24 cells showed the least mutual cohesion and the original C-1 cells showed the most. The possibility that an alteration in cellular membrane might be related to an increase in the resistance to radiosensitizing agents was discussed

Interphase death of dividing cells. Kinetics of death of cultured Chinese hamster fibroblasts after irradiation with various doses

International Nuclear Information System (INIS)

Kublik, L.N.; Veksler, A.M.; Ehjdus, L.Kh.

1989-01-01

In studying the kinetics of interphase death (ID) of cultured Chinese hamster cells after irradiation with doses of 100 to 800 Gy the authors showed an increase in the ID rate with increasing radiation dose; the presence of serum in the medium both during and after irradiation prevents the cell death

Improving the secretory capacity of Chinese hamster ovary cells by ectopic expression of effector genes: Lessons learned and future directions

DEFF Research Database (Denmark)

Hansen, Henning Gram; Pristovsek, Nusa; Kildegaard, Helene Faustrup

2017-01-01

Chinese hamster ovary (CHO) cells are the preferred cell factory for the production of therapeutic glycoproteins. Although efforts primarily within bioprocess optimization have led to increased product titers of recombinant proteins (r-proteins) expressed in CHO cells, post-transcriptional bottle...

Effects of chronic fly ash exposure on golden hamsters: changes in lung phospholipids and their fatty acid composition as a result of inhalation

Energy Technology Data Exchange (ETDEWEB)

Nishimura, I; Negishi, T; Kamihira, M

1986-01-01

Changes in lung phospholipids of golden hamsters exposed to 2 mg/mT coal fly ash for 180 days, 7 days/week, 20 hours/day were examined. In the exposed group the amount of phospholipids in lavaged lung organ increased significantly compared with the control group, but in pulmonary surfactant did not. As regards lipid composition of phospholipids in lavaged lung organ, phosphatidylcholine was slightly increased but sphingomyelin was decreased by exposure. Some significant changes in fatty acid composition of phospholipids were observed between exposed and control group. In pulmonary surfactant, palmitic acid showed no change but myristic acid and oleic acid decreased. On the other hand, in lavaged lung organ, palmitic acid increased but stearic acid and decosatetraenoic acid decreased. Arachidonic acid composition increased in both parts of lung. An increase in the proportion of polyunsaturated fatty acid in whole fatty acid of phospholipids was found in pulmonary surfactant of exposed hamsters. 24 refs., 2 figs., 3 tabs.

UV-sensitivity of bromodeoxyuridine (BUdR)-substituted chromosomes in Chinese hamster cells

International Nuclear Information System (INIS)

Antoshchina, M.M.; Luchnik, N.V.

1990-01-01

Chinese hamster cells with chromosomes differently substituted for BUdR (TT-TT, TT-TB, TB-TB, TB-BB, where T is thymidine containing chromatid and B is BUdR substituted chromatid) were exposed to UV-light in phase G 2 and chromosome aberrations (mainly chromatid breaks) were analysed. Breaks frequency per chromosome was proportional to BUdR content. No breaks were found in TT-TT chromosomes. The frequency of breaks per TB chromatid was similar with TT-TB and TB-BB chromosomes. In TB-BB chromosomes, however, virtually no breaks occured in TB chromatids whereas in BB chromatids, their frequency was much higher than was expected

Comparison of the subcellular distribution of monomeric 239Pu and 59Fe in the liver of rat, mouse, and Syrian and Chinese hamsters

International Nuclear Information System (INIS)

Winter, R.; Seidel, A.

1982-01-01

The subcellular distribution of 239 Pu and 59 Fe 10 days after intravenous injection as a citrate complex was investigated by sucrose density gradient centrifugation in the liver of rat, mouse, and Syrian and Chinese hamsters. Lysosomes were separated from other cell constituents by injection of the nonionic detergent Triton WR 1339 4 days before sacrifice. The Triton-induced decrease in the density of the lysosomes was very similar in all four animal species and was followed closely by a corresponding decrease of the median density of the 239 Pu profiles in rat, mouse, and, to a smaller extent, Syrian hamster. However, in Chinese hamster a clear correspondence between lysosomes and 239 Pu was not found 10 days after nuclide injection. It was concluded that lysosomes are the main storage organelles fo 239 Pu in the liver of rat and mouse and that in all four animal species mitochondria and endoplasmic reticulum do not play any significant role in binding the radionuclide. The relevance of pericellular membranes has to be checked. The distribution patterns of 59 Fe and 239 Pu were quite different

Effects of 1 MHz ultrasound on Chinese hamster V-79 cells: cavitational mechanisms and effects on proliferation

International Nuclear Information System (INIS)

Ciaravino, V.

1982-01-01

An assessment of acoustic cavitation as a primary physical mechanism in producing chemical and biological effects has been made. Chemical effects have been demonstrated through experimental protocols involving the release of iodine from sodium iodide. Biological effects have been shown by procedures assessing cell lysis and growth of in vitro Chinese hamsters V-79 cells. An important conclusion reached through these assessments is that the threshold level at which acoustic cavitation can exert an effect is dependent on the sensitivity of the experimental system being exposed. The proliferation of mitotically synchronous in vitro Chinese hamster V-79 cells exposed to 1 MHz ultrasound was investigated. Cell growth was assessed in the first three hours after sonication (3 W/cm 2 for 1 min) and was found to decrease to approx. 60 percent of control values. At an intensity of 3 W/cm 2 and exposure durations of 0.1, 1, 2, 5, and 10 min., mitotic cells underwent respectively increasing amounts of lysis. The remaining intact cells were observed for growth rate as indicated by the timed formation of colonies from single cells. The results indicated an immediate decrease in colony size (p 0.05)

Adriamycin resistance, heat resistance and radiation response in Chinese hamster fibroblasts

International Nuclear Information System (INIS)

Wallner, K.; Li, G.

1985-01-01

Previous investigators have demonstrated synergistic interaction between hyperthermia and radiation or Adriamycin (ADR), using cell lines that are sensitive to heat or ADR alone. The authors investigated the effect of heat, radiation or ADR on Chinese hamster fibroblasts (HA-1), their heat resistant variants and their ADR resistant variants. Heat for ADR resistance did not confer cross resistance to radiation. Cells resistant to heat did show cross resistance to ADR. While cells selected for ADR resistance were not cross resistant to heat, they did not exhibit drug potentiation by hyperthermia, characteristic of ADR sensitive cells. Cytofluorometric measurement showed decreased ADR uptake in both heat and ADR resistant cells. The possibility of cross resistance between heat and ADR should be considered when designing combined modality trials

Mutation of Chinese hamster cells by near-UV activation of promutagens

International Nuclear Information System (INIS)

Barnhart, B.J.; Cox, S.H.

1980-01-01

A tissue-culture assay for mutagenesis and cytotoxicity incorporating near ultraviolet (NUV) light activation of polyaromatic hydrocarbons (PAH) has been developed. Cultures of Chinese hamster cells (line CHO) growing in suspension culture were inoculated with benzo[a]pyrene (B[a]P), 7,12-dimethylbenzanthracene (DMBA) or shale-oil retort-water and exposed to light from a high-pressure mercury lamp fitted with a Corning NUV bandpass filter. This light source both permitted activation of PAH and the shale-oil water and precluded detectable damage to DNA. Neither the PAH nor the NUV alone had any effect on cell survival or mutation frequencies but the chemicals plus NUV were extremely effective in producing mutations to 6-thioguanine resistance (hgprt gene). (orig.)

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

International Nuclear Information System (INIS)

Winter, R.; Seidel, A.

1980-01-01

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 239 Pu administration. The animals were sacrificed 4 days later. In order to study the possible association with ferritin, 59 Fe 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 239 Pu 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.)

Chinese hamster pleiotropic multidrug-resistant cells are not radioresistant

International Nuclear Information System (INIS)

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

1988-01-01

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

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

International Nuclear Information System (INIS)

Ventura, A.M.

1987-01-01

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)

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

OpenAIRE

Kaina, B; Lohrer, H; Karin, M; Herrlich, P

1990-01-01

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 re...

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

International Nuclear Information System (INIS)

Nairn, R.S.; Humphrey, R.M.; Adair, G.M.

1988-01-01

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)

Isolation and structure determination of the intact sialylated N-linked carbohydrate chains of recombinant human follitropin expressed in Chinese hamster ovary cells

NARCIS (Netherlands)

Vliegenthart, J.F.G.; Hård, K.; Mekking, A.; Damm, J.B.L.; Kamerling, J.P.; Boer, W. de; Wijnands, R.A.

1990-01-01

Biologically active recombinant human follitropin has been expressed in Chinese hamster ovary cells. The carbohydrate chains of the recombinant glycoprotein hormone were enzymatically released by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. The oligosaccharides were separated from

Variations in sensitivity of synchronized Chinese hamster cells to oxic and anoxic X-ray exposures

International Nuclear Information System (INIS)

Siracka, E.; Littbrand, B.; Clifton, K.H.; Revesz, L.

1975-01-01

V-79 Chinese hamster cells in monolayer cultures on glass surfaces were synchronized by treatment with hydroxyurea and then exposed at different times to X-rays in air or in oxygen-free argon. Survival determinations indicated that the oxygen enhancement ratio (OER) as expressed by the ratio of the respective D 0 values varied over a narrow range in the different phases of the cell cycle. These changes resulted from cyclic alterations in both aerobic and anaerobic D 0 values, possibly in n values. (author)

Interchromosomal distribution of gamma ray-induced chromatid aberrations in Chinese hamster ovary cells

International Nuclear Information System (INIS)

Martinez-Lopez, Wilner; Porro, Valentina; Folle, Gustavo A.; Mendez-Acuna, Leticia; Obe, Guenter; Savage, John R.K.

2000-01-01

Inter chromosomal distributions of breakpoints from chromatid-type aberrations induced by gamma rays in Chinese hamster ovary cells were analyzed. In most chromosomes the distribution was as expected from chromosome lengths for simple breaks or the respective relative corrected length in case of exchanges. There were deviations from expectation in a few chromosomes for chromatid breaks, interchanges, intra-arm intra changes and inter-arm intra changes. Especially interesting are the results concerning chromosomes 2 and 8, which were more often involved in exchanges than expected. An 'exchange phenotype' for these chromosomes is proposed and possible explanations for the nonrandom distribution of chromosome breakpoints are presented. (author)

Clearance of Free Silica in Rat Lungs by Spraying with Chinese Herbal Kombucha

Directory of Open Access Journals (Sweden)

Nai-fang Fu

2013-01-01

Full Text Available The effects of spraying with kombucha and Chinese herbal kombucha were compared with treatments with tetrandrine in a rat silicosis model. Silica dust (50 mg was injected into the lungs of rats, which were then treated with one of the experimental treatments for a month. The rats were then killed and the effects of the treatments were evaluated by examining the extent and severity of the histopathological lesions in the animals’ lungs, measuring their organ coefficients and lung collagen contents, determining the dry and wet weights of their lungs, and measuring the free silica content of the dried lungs. In addition, lavage was performed on whole lungs taken from selected rats, and the numbers and types of cells in the lavage fluid were counted. The most effective treatment in terms of the ability to reduce lung collagen content and minimize the formation of pulmonary histopathological lesions was tetrandrine treatment, followed by Chinese herbal kombucha and non-Chinese herbal kombucha. However, the lavage fluid cell counts indicated that tetrandrine treatment had severe adverse effects on macrophage viability. This effect was much less pronounced for the kombucha and Chinese herbal kombucha treatments. Moreover, the free silica levels in the lungs of animals treated with Chinese herbal kombucha were significantly lower than those for any other silica-exposed group. These preliminary results indicate that spraying with Chinese herbal kombucha preparations can effectively promote the discharge of silica dust from lung tissues. Chinese herbal kombucha inhalation may thus be a useful new treatment for silicosis and other pneumoconiosis diseases.

Clearance of free silica in rat lungs by spraying with chinese herbal kombucha.

Science.gov (United States)

Fu, Nai-Fang; Luo, Chang-Hui; Wu, Jun-Cai; Zheng, Yan-Yan; Gan, Yong-Jin; Ling, Jian-An; Liang, Heng-Qiu; Liang, Dan-Yu; Xie, Jing; Chen, Xiao-Qin; Li, Xian-Jun; Pan, Rui-Hui; Chen, Zuo-Xing; Jiang, Sheng-Jun

2013-01-01

The effects of spraying with kombucha and Chinese herbal kombucha were compared with treatments with tetrandrine in a rat silicosis model. Silica dust (50 mg) was injected into the lungs of rats, which were then treated with one of the experimental treatments for a month. The rats were then killed and the effects of the treatments were evaluated by examining the extent and severity of the histopathological lesions in the animals' lungs, measuring their organ coefficients and lung collagen contents, determining the dry and wet weights of their lungs, and measuring the free silica content of the dried lungs. In addition, lavage was performed on whole lungs taken from selected rats, and the numbers and types of cells in the lavage fluid were counted. The most effective treatment in terms of the ability to reduce lung collagen content and minimize the formation of pulmonary histopathological lesions was tetrandrine treatment, followed by Chinese herbal kombucha and non-Chinese herbal kombucha. However, the lavage fluid cell counts indicated that tetrandrine treatment had severe adverse effects on macrophage viability. This effect was much less pronounced for the kombucha and Chinese herbal kombucha treatments. Moreover, the free silica levels in the lungs of animals treated with Chinese herbal kombucha were significantly lower than those for any other silica-exposed group. These preliminary results indicate that spraying with Chinese herbal kombucha preparations can effectively promote the discharge of silica dust from lung tissues. Chinese herbal kombucha inhalation may thus be a useful new treatment for silicosis and other pneumoconiosis diseases.

Chromosome aberration frequency in blood lymphocytes of animals with 239Pu lung burdens

International Nuclear Information System (INIS)

Brooks, A.L.; LaBauve, R.J.; McClellan, R.O.; Jensen, D.A.

1976-01-01

Other investigators have suggested a causal relationship between accidental 239 Pu exposures in man and the presence of chromosome aberrations in blood lymphocytes. For experimental assessment of this relationship, 16 rhesus monkeys and 171 Chinese hamsters were exposed to 239 PuO 2 aerosols and an additional five hamsters were injected with 239 Pu citrate, and the frequency of aberrations in blood lymphocyte was determined. Hamsters with the highest lung burden had a median survival time of about 80 days. No deaths occurred in any of the other treated hamsters or monkeys by 250 days after 239 Pu inhalation. Hamsters sacrificed at 30 days showed an increase in chromosome aberration frequency with increasing dose to lungs. By 120 days after inhalation, the aberration frequency in the controls was 0.012. The frequency in animals with doses that produced significant life shortening had decreased to 0.018 and to 0.032 aberration/cell in animals with lower doses. At 380 days after injection of 2 nCi of 239 Pu citrate per gram of body weight, hamster lymphocytes had an aberration frequency of 0.048 aberration/cell. The level of chromosome damage in the 239 PuO 2 -exposed monkeys at 30 and 90 days after inhalation was not different from that observed in controls. Possible reasons for differences between the experimental animal observations and findings in man are discussed

Effects of preventing O-glycosylation on the secretion of human chorionic gonadotropin in Chinese hamster ovary cells

International Nuclear Information System (INIS)

Matzuk, M.M.; Krieger, M.; Corless, C.L.; Boime, I.

1987-01-01

Human chorionic gonadotropin (hCG) is a member of a family of heterodimeric glycoprotein hormones that have a common α subunit but differ in their hormone-specific β-subunits. The β subunit of hCG (hCGβ) is unique among the β subunits in that it contains four mucin-like O-linked oligosaccharides attached to a carboxyl-terminal extension. To study the effects of O-glycosylation on the secretion and assembly of hCG, expression vectors containing either hCGβ gene alone or together with the hCGα gene were transfected into a mutant Chinese hamster ovary cell line, 1d1D, which exhibits a reversible defect in O-glycosylation. The results reveal that hCGβ can be secreted normally in the absence of its O-linked oligosaccharides. hCGβ devoid of O-linked carbohydrate can also combine efficiently with hCGα and be secreted as an intact dimer. The authors conclude that in Chinese hamster ovary cells, the hCGβ O-linked chains play no role in the assembly and secretion of hCG. The normal and O-linked oligosaccharide-deficient forms of hCG secreted by these cells should prove useful in examining the role of O-linked chains on the biological function of hCG

Detection of extracellular neutrophil elastase in hamster lungs after intratracheal instillation of E. coli lipopolysaccharide using a fluorogenic, elastase-specific, synthetic substrate.

Science.gov (United States)

Rudolphus, A.; Stolk, J.; van Twisk, C.; van Noorden, C. J.; Dijkman, J. H.; Kramps, J. A.

1992-01-01

Repeated intratracheal instillations of E. coli lipopolysaccharide (LPS) in hamster lungs cause an influx of polymorphonuclear leukocytes (PMNs) into the alveolar walls, with concomitant development of severe emphysema. It has been suggested that elastase, released by these PMNs, is involved in the development of emphysema. This study demonstrates the release of elastase from recruited PMNs in cryostat sections of hamster lungs, after being treated once, twice, or thrice with LPS, intratracheally. Elastase activity was visualized using two elastase-specific synthetic substrates, to which a methoxynaphthylamine (MNA) group had been bound covalently. Liberated MNA, when made insoluble by coupling with 5-nitrosalicylaldehyde, fluoresces strongly. The authors observed that the interval between start of incubation and appearance of fluorescence and the intensity of fluorescence correlated with the number of LPS administrations. Fluorescence was observed to be located in or in close vicinity to alveolar walls. No fluorescence was observed in sections of untreated hamsters. Liberation of MNA from synthetic substrates was delayed strongly by the addition of a recombinant secretory leukocyte proteinase inhibitor or a substituted cephalosporin neutrophil elastase inhibitor. The authors conclude that LPS-mediated PMN influx into the lung is accompanied by release of elastase from these cells and speculate that this PMN-elastase is involved in the development of LPS-mediated emphysema. Images Figure 1 Figure 2 Figure 3 PMID:1632460

Survival and kinetics of Chinese hamster ovary cell subpopulations induced by Adriamycin and radiation

International Nuclear Information System (INIS)

Schneiderman, M.H.

1979-01-01

Mitotic selection of Chinese hamster ovary (CHO) cells, at 10 min intervals after the initiation of Adriamycin and/or x-ray treatment was used to measure the kinetics and survival of cells which progressed without delay, the ''refractory'' cells, the cells that reached mitosis only after recovery from the treatment-induced delay, the ''recovered'' cells, and the survival of the cells remaining attached to the flask 5 h after treatment. The cell kinetics were determined from the rate at which cells entered mitosis, and the reproductive integrity from the survival of the selected refractory, recovered and remaining (unselected) cells

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.

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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.

Cell-cycle distributions and radiation responses of Chinese hamster cells cultured continuously under hypoxic conditions

International Nuclear Information System (INIS)

Tokita, N.; Carpenter, S.G.; Raju, M.R.

1984-01-01

Cell-cycle distributions were measured by flow cytometry for Chinese hamster (CHO) cells cultured continuously under hypoxic conditions. DNA histograms showed an accumulation of cells in the early S phase followed by a traverse delay through the S phase, and a G 2 block. During hypoxic culturing, cell viability decreased rapidly to less than 0.1% at 120 h. Radiation responses for cells cultured under these conditions showed an extreme radioresistance at 72 h. Results suggest that hypoxia induces a condition similar to cell synchrony which itself changes the radioresistance of hypoxic cells. (author)

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. [UNESP; 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 ...

Using titer and titer normalized to confluence are complementary strategies for obtaining Chinese hamster ovary cell lines with high volumetric productivity of etanercept

DEFF Research Database (Denmark)

Pristovšek, Nuša; Hansen, Henning Gram; Sergeeva, Daria

2018-01-01

The selection of clonally-derived Chinese hamster ovary (CHO) cell lines with the highest production rate of recombinant glycoproteins remains a big challenge during early stages of cell line development. Different strategies using either product titer or product titer normalized to cell number...

Protection of ionizing radiation-induced cytogenetic damage by hydroalcoholic extract of Cynodon dactylon in Chinese hamster lung fibroblast cells and human peripheral blood lymphocytes.

Science.gov (United States)

Rao, Bola Sadashiva Satish; Upadhya, Dinesh; Adiga, Satish Kumar

2008-01-01

The radiomodulatory potential of hydroalcoholic extract of a medicinal plant Cynodon dactylon (family: Poaceae) against radiation-induced cytogenetic damage was analyzed using Chinese hamster lung fibroblast (V79) cells and human peripheral blood lymphocytes (HPBLs) growing in vitro. Induction of micronuclei was used as an index of cytogenetic damage, evaluated in cytokinesis blocked binucleate cells. The hydroalcoholic Cynodon dactylon extract (CDE) rendered protection against the radiation-induced DNA damage, as evidenced by the significant (p<0.001) reduction in micronucleated binucleate cells (MNBNC%) after various doses of CDE treatment in V79 cells and HPBLs. The optimum dose of CDE (40 and 50 microg/ml in HPBLs and V79 cells, respectively) with the greatest reduction in micronuclei was further used in combination with various doses of gamma radiation (0.5, 1, 2, 3, and 4 Gy) exposed 1 h after CDE treatment. A linear dose-dependent MNBNC% increase in radiation alone group was observed, while 40/50 microg/ml CDE significantly resulted in the reduction of MNBNC%, compared to the respective radiation alone groups. CDE resulted in a dose-dependent increase in free radical scavenging ability against various free radicals, viz., 2, 2-diphenyl-2-picryl-hydrazyl (DPPH); 2, 2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS); superoxide anion (O2*-); hydroxyl radical (OH*) and nitric oxide radical (NO*) generated in vitro. Also, an excellent (70%) inhibition of lipid peroxidation in vitro was observed at a dose of 300 microg/ml CDE, attaining the saturation point at higher doses. The present findings demonstrated the radioprotective effect of CDE, also rendering protection against radiation-induced genomic instability and DNA damage. The observed radioprotective effect may be partly attributed to the free radical scavenging and antilipid peroxidative potential of CDE.

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...... using omics tools. A wide range of methods were applied including whole-genome sequencing, targeted genome sequencing, mRNA sequencing, miRNA sequencing and mass spectrometry based shotgun proteomics on a number of clones in order to get a more holistic picture of the inner workings of these CHO...... transfectants. From the whole-genome sequencing of two CHO genomes (CHO DXB11 and the FVIII producing transfectant: F435) it was observed that roughly 20% of the genes in the genome were haploid and roughly 10% had a copy number of three or higher indicating extensive rearrangements compared to the Chinese...

Ultra-fast repair of single-strand breaks in DNA of. gamma. -irradiated Chinese hamster cells

Energy Technology Data Exchange (ETDEWEB)

Leontjeva, G A; Mantzighin, Yu A; Gaziev, A I [AN SSSR, Pushchino-na-Oke. Inst. Biologicheskoj Fiziki

1976-12-01

Studies of the effect of thermal treatment of Chinese hamster cells on sedimentation of DNA in the alkaline sucrose gradient showed that heating the cells to 68/sup 0/C for 15 min caused the same degradation as ..gamma..-irradiation with 5 to 7 krad at 37/sup 0/C. The inhibition of cellular repair enzymes by heating was therefore unacceptable. The process of ultra-fast repair is essentially determined by the DNA-ligase reaction, which is activated in the presence of Mg ions, and inhibited in mammalian cells in the presence of EDTA and pyrophosphate. Sedimentation profiles were therefore measured for the DNA of Chinese hamster cells ..gamma..-irradiated (5 krad) at 0/sup 0/C or 22/sup 0/C in the presence of Mg/sup + +/, or EDTA and pyrophosphate, and the results demonstrated ultra-fast repair only at 20 to 37/sup 0/C, in contrast to bacteria. A study was made of the temperature dependence of the activity of the DNA ligases isolated from E.coli and rabbit bone marrow. The NAD-dependent bacterial DNA ligase was active at temperatures from 0 to 40/sup 0/C, whereas ATP-dependent DNA ligase of mammals only showed activity in the range 15 to 40/sup 0/C. The differing temperature dependences of ultra-fast repair in bacterial and mammalian cells are in agreement with the temperature dependences of the activities of isolated enzymes, and the results suggest that the process of ultra-fast repair of single-strand breaks of DNA takes place in both bacterial and mammalian cells.

Histochemical, light and electron microscopic study of polonium-210 induced peripheral tumours in hamster lungs -evidence implicating the Clara Cell as the cell of origin

International Nuclear Information System (INIS)

Kennedy, A.R.; McGandy, R.B.; Little, J.B.

1977-01-01

Peripheral lung tumors induced in Syrian golden hamsters by intratracheally administered polonium-210 ( 210 Po) are similar to the peripheral lung tumours induced in many species by a variety of carcinogens. In addition, they show many of the histopathological features observed in human bronchiolar-alveolar carcinomas. Serial sacrifice studies of hamsters exposed to multiple instillations of 210 Po have been carried our to identify the cell of origin of these tumors. By means of thin, plastic (glycol methacrylate) sections, electron microscopy, and histochemistry, it is concluded that the bronchiolar Clara cell is the probable cell of origin, and that this view is generally compatible with many of the reported cytological characteristics of the human tumor. (author)

Methylmethane-sulphonate and X-ray-induced mutations in the Chinese hamster hprt gene: mRNA phenotyping using polymerase chain reactions

International Nuclear Information System (INIS)

Chaudhry, M.A.; Fox, Margaret

1990-01-01

Alterations in the hprt gene of Chinese hamster cells were determined in 71 spontaneous, methylmethane sulphonate (MMS)-and X-ray induced mutants, using the Southern blot hybridization technique. To investigate the possibility of small deletions, MMS-induced mutants were studied with proves derived from exons 3 and 9 but no evidence of specific deletion of these two exons was found. The polymerase chain reaction (PCR) was used to phenotype hprt transcripts in 48 MMS, X-ray and spontaneous Chinese hamster mutants by amplifying the coding region of their cDNA. Among 22 MMS-induced mutants the message was present in 16 instances. An analysis of 20 X-ray-induced mutants showed the presence of hprt mRNA in 11 of them with five having low levels of transcription. Among six spontaneous mutants, four were negative for mRNA on standard Northern blots and in one the message was only detected after PCR amplification. Direct DNA sequencing of 10 mutants revealed the presence of base substitutions in five of them while a 7 bp deletion was found in another. No mutations were found in another four mutants, suggesting the presence of mutation outside the coding region. (author)

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....... Homologs of most human glycosylation-associated genes are present in the CHO-K1 genome, although 141 of these homologs are not expressed under exponential growth conditions. Many important viral entry genes are also present in the genome but not expressed, which may explain the unusual viral resistance...... property of CHO cell lines. We discuss how the availability of this genome sequence may facilitate genome-scale science for the optimization of biopharmaceutical protein production....

A physiological threshold for protection against menadione toxicity by human NAD(P)H : quinone oxidoreductase (NQO1) in Chinese hamster ovary (CHO) cells

NARCIS (Netherlands)

Haan, de L.H.J.; Boerboom, A.M.J.F.; Rietjens, I.M.C.M.; Capelle, van D.; Ruijter, de A.J.M.; Jaiswal, A.K.; Aarts, J.M.M.J.G.

2002-01-01

NAD(P)H:quinone oxidoreductase 1 (NQO1) has often been suggested to be involved in cancer prevention by means of detoxification of electrophilic quinones. In the present study, a series of Chinese hamster ovary (CHO) cell lines expressing various elevated levels of human NQO1 were generated by

Effect of secondary radiation from 70 GeV protons and γ-quanta on Chinese hamster chromosomes depending on the cell cycle stage

International Nuclear Information System (INIS)

Antipov, A.V.; Aptikaeva, G.F.; Akhmadieva, A.Kh.; Ganassi, E.Eh.; Zaichkina, S.I.; Livanova, I.A.; Smirnova, E.N.

1987-01-01

In cultured Chinese hamster cells, no decrease in the number of chromosome aberrations was noted after exposure thereof to 70 GeV protons at the late S-phase as opposed to early one. It is suggested that high biological effectiveness of this type of raiation is associated with its inhibiting effect of cytogenetic damages repair

Cell killing and mutation induction on Chinese hamster cells by photoradiations

International Nuclear Information System (INIS)

Lam, C.K.C.

1982-01-01

The subject matter of this investigation concerns the killing and mutagenic effects induced by far-UV radiation and broad spectra of black, white and gold lights. Applying radiation directly on CHO (Chinese hamster ovary) 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 (6TG), ouabain and diptheria toxin (DT). Cells in the G1/early S boundary are the most sensitive to far-UV or unfiltered fluorescent lights. When synchronous cells are irradiated with moderate doses of far-UV or unfiltered broad spectra of black light, mutations to 6-TG and ouabain resistance are slightly higher in early S period than in the remaining parts of the cell cycle. Mutation induction of 6-TG, ouabain or DT resistance is increased in the split-dose samples of the asynchronous and synchronous CHO cells. CHO cells predominantly express an error-prone repair mechanism after photoirradiation

Traditional Chinese medicine as adjunctive therapy improves the long-term survival of lung cancer patients.

Science.gov (United States)

Liao, Yueh-Hsiang; Li, Chia-Ing; Lin, Cheng-Chieh; Lin, Jaung-Geng; Chiang, Jen-Huai; Li, Tsai-Chung

2017-12-01

Traditional Chinese medicine is one of the popular alternative treatments for cancer, mainly enhancing host immune response and reducing adverse effect of chemotherapy. This study first explored traditional Chinese medicine treatment effect on long-term survival of lung cancer patients. This study evaluated whether traditional Chinese medicine combined with conventional cancer treatment improved overall survival of lung cancer patients. We had conducted a retrospective cohort study on 111,564 newly diagnosed lung cancer patients in 2000-2009 from National Health Insurance Program database. A total of 23,803 (21.31%) patients used traditional Chinese medicine for lung cancer care. Eligible participants were followed up until 2011 with a mean follow-up period of 1.96 years (standard deviation 2.55) for non-TCM users and 3.04 years (2.85) for traditional Chinese medicine users. Patients with traditional Chinese medicine utilization were significantly more likely to have a 32% decreased risk of death [hazard ratio = 0.62; 95% confidence interval = 0.61-0.63], compared with patients without traditional Chinese medicine utilization after multivariate adjustment. We also observed a similar significant reduction risk across various subgroups of chronic lung diseases. Qing Zao Jiu Fei Tang was the most effective traditional Chinese medicine agent for mortality reduction both in the entire lung cancer (0.81; 0.72-0.91) and matched populations (0.86; 0.78-0.95). This study demonstrated adjunctive therapy with traditional Chinese medicine may improve overall survival of lung cancer patients. This study also suggested traditional Chinese medicine may be used as an adjunctive therapy for cancer treatment. These observational findings need being validated by future randomized controlled trials to rule out the possibility of effect due to holistic care.

Comparative study on fast neutrons radiobiological effect on Chinese hamster cells in culture depending on regime of irradiation

International Nuclear Information System (INIS)

Elisova, T.V.; Feoktistova, T.P.; Stavrakova, N.M.

1988-01-01

Comparative study of regularities of fast neutron radiobiological effect on Chinese hamster cells in culture under pulse and statistic irradiation regimes that was estimated by reproductive death of cells and induced frequency of resistence mutations to 6-tioguanine is carried out. It is stated that with the dose rate increase approximately by 6 orders radiobiological efficiency of fast neutrons decreases. It is suggested that one of the causes of decreasing pulse irradiation efficiency are processes on radiation-chemical level. 9 refs.; 3 figs

The cytogenetic effect of radiation and postirradiation treatment of Chinese hamster cells with arabinoside cytosine and hydroxyurea

International Nuclear Information System (INIS)

Elisova, T.V.; Stavrakova, N.M.; Feoktistova, T.P.

1988-01-01

A two-hour treatment of Chinese hamster cells at the G 1 stage of the cell cycle with arabinoside cytocine combined with hydroxyurea after X-irradiation (50-300 cGy) produced a 2- to 4-fold increase in the frequency of chromosome aberrations. The mitotic selection method was used to synchronize the cells. The potentiating effect of inhibitors was estimated by the yield of centric exchanges decreased with increasing radiation dose. It is suggested that DNA repair processes determining a linear component of the dose-response curve are modified within the dose-range under study

Vitamin K metabolism in Chinese Hamster Ovary cells

International Nuclear Information System (INIS)

Hoffman, H.S.

1986-01-01

Recent investigations suggest that vitamin K may have functions other than in blood coagulation and calcification. The present study was undertaken to investigate this hypothesis using cells in culture. Chinese Hamster Ovary (CHO) cells were chosen due to their active metabolism and growth and lack of similarity to liver and bone cells, in which vitamin K metabolism is well known. Cells were adapted to serum-free media, incubated in media containing the appropriate concentrations of vitamin K for specified times, scraped from plates, pelleted, extensively washed to remove adhering vitamin K, extracted with chloroform:methanol (2:1, v/v) and analyzed on C18 HPLC columns. Uptake of vitamin K by CHO cells follows saturation kinetics at vitamin K concentrations up to 25 μ M and is transported into cells at the rate of 10 pmol/min. 10 6 cells. After 24 hours, 3 H vitamin K is metabolized by CHO cells to several compounds, the major of which was isolated and identified as vitamin K epoxide. In 3 experiments, after 24 hours, the average cellular uptake of vitamin K was 8% with approximately half being metabolized to vitamin K epoxide. These results demonstrate that vitamin K is metabolized in cells with widely different functions and suggest a generalized function for vitamin K which has yet to be elucidated

Effects of ultrasound, cysteamine, and x-rays on V79 Chinese hamster cells

International Nuclear Information System (INIS)

Fu, Y.K.

1978-01-01

Chinese hamster V79 cells were exposed to different intensities and durations of 1 MHz ultrasound and were studied for cell lysis and colony-forming ability. The threshold for cell lysis and loss of viability (reduction in colony-forming ability) were found to be ultrasonic intensity, sonication duration, and energy dependent. Above the threshold there was an initial correlation between ultrasound intensity and biological effect: the higher the intensity, the greater the amount of cell lysis and reduction in colony-forming ability. These effects were maximal at an intensity of 10-20 W/cm 2 , and were less at 30 W/cm 2 . Cells were also exposed to ultrasound in the presence of cysteamine and results are compared with the effects of x radiation on cells exposed in the presence of cysteamine or methionine

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

International Nuclear Information System (INIS)

Olive, P.L.; Vanderbyl, S.; MacPhail, S.H.

1991-01-01

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

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)

Losada, Raquel; Rivero, Maria Teresa; Slijepcevic, Predrag; Goyanes, Vicente; Fernandez, Jose Luis

2005-01-01

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

Nuclear scaffold organization in the X-ray sensitive Chinese hamster mutant cell line, xrs-5

International Nuclear Information System (INIS)

Yasui, L.S.; Fink, T.J.; Enrique, A.M.

1994-01-01

Nuclear organization was probed in the radiation-sensitive Chinese hamster ovary (CHO) cell line, xrs-5, and compared with parental CHO K1 cells using the resinless section technique and DNase I digestions. The resinless section data showed no gross morphological differences in core filaments from the nuclear scaffolds of unirradiated CHO K1 and xrs-5 cells. However, the nuclear scaffolds of irradiated xrs-5 cells (1 Gy) had significantly increased ground substance. Irradiated and unirradiated CHO K1 cell nuclear scaffolds were morphologically identical. These data suggest that both CHO K1 and xrs-5 cell nuclear scaffolds had internal nuclear scaffolding networks that could provide DNA attachment sites. (author)

Cloning and Expression of Luteinizing Hormone Subunits in Chinese Hamster Ovary Cell Line

Directory of Open Access Journals (Sweden)

Zeinab Soleimanifar

2016-10-01

Full Text Available Background: Luteinizing hormone (LH was secreted by the stimulating cells of the testes and ovaries in the anterior pituitary gland. The application of this hormone is in the treatment of men and women with infertility and amenorrhea respectively.Materials and Methods: In the present study the alpha and beta subunits of human LH gene were cloned into the pEGFP-N1 expression vector and produced the recombinant LH hormone in Chinese hamster ovary (CHO eukaryotic system.Results: Alpha and beta subunits of LH hormone were cloned between NheI and BamHI cut sites of pEGFP_N1 expression plasmid and confirmed by PCR.  Hormone expression was evaluated in CHO cell line by Western blotting using the specific antibody.Conclusion: Alpha and beta subunits of LH hormone were expressed in CHO cell line perfectly.

Hypermutability of a UV-sensitive aphidicolin-resistant mutant of Chinese hamster fibroblasts

International Nuclear Information System (INIS)

Liu, P.K.; Chang, C.; Trosko, J.E.

1982-01-01

An ultraviolet light (UV)-sensitive thymidine auxotroph of Chinese hamster V79 cells that exhibits pleiotropic effects such as a high level of deoxycytidine triphosphate, slow growth, sensitivity to cytidine, and high frequencies of site-specific bromodeoxyuridine-dependent chromosomal aberrations was selected by its resistance to aphidicolin. The UV-induced mutability of this mutant and one of its revertants, which retains some of the phenotypes listed above, was studied in 3 mutation assay systems. The results showed that the mutant was hypermutable for ouabain and diphtheria-toxin-resistant mutations compared to wild-type V79 cells at the same UV dose or the same survival level. The mutant exhibits a delayed expression of maximal frequency of induced 6-thioguanine-resistant mutants. When maximal frequencies are compared at the same UV dose, the mutant also has higher mutation frequencies at the hypoxanthine-guanine phosphoribosyl transferase locus. The revertant was similar to the wild-type in UV sensitivity and mutability. (orig./AJ)

Ferritin-iron increases killing of Chinese hamster ovary cells by X-irradiation

International Nuclear Information System (INIS)

Nelson, J.M.; Stevens, R.G.

1992-01-01

Stationary-phase Chinese hamster ovary cells were cultured in medium containing ferritin (∼19% iron by weight) added at concentrations ranging from 0 to 128 μg/ml. One set of cultures was unirradiated, another set exposed to 4.0 Gy of X-ray. Clonogenic cell survival was assessed in each set of cultures. In the absence of added ferritin, 4.0 Gy killed approximately 50% of the cells. In the absence of radiation, ferritin was not toxic at less than 48 μg/ml; above 48 μg/ml, toxicity increased with concentration. Apoferritin was not toxic at any concentration tested (up to 1000 μg/ml). Although 32 μg/ml ferritin, reflecting only a 3-6 fold increase in iron concentration over normal serum, was not toxic, it reduced survival of X-irradiated cells by an additional 75%. These results indicate that a sublethal concentration of ferritin can be a potent radiosensitizer. (Author)

Radiation-induced mutagenicity in repair deficient Chinese hamster ovary (CHO) mutants

International Nuclear Information System (INIS)

Tesmer, J.G.; Saunders, E.H.; Chen, D.J.

1987-01-01

To determine if there is a relationship between DNA double-strand break repair and mutagenicity the authors utilized two x-ray sensitive mutants of Chinese hamster ovary cells along with the parental line K1. The two mutant lines xrs-5 and xrs-6, which have different DSB repair capabilities, were used to determine cell killing and 6-thioguanine resistance (6TG/sup r/) mutation frequencies induced by either x-rays of α-particles, x-ray survival data indicated the two mutant lines have similar sensitivity and are 5-7 fold more sensitive than the parental line K1. The mutant lines are also sensitive to α-particles but to a lesser extent. The authors' 6TG mutation data indicated that the two mutant lines are hypermutable. When mutation frequencies were plotted against the log of survival, mutation frequency at a given survival level was greater in mutant cell population than in parental K1 cells. Their results support the notion that repair of DSB play an important role in the expression of radiation-induced cell killing and mutagenicity

Isolation and characterization of a radiosensitive Chinese hamster ovary cell line

International Nuclear Information System (INIS)

Fuller, L.F.

1987-01-01

A x-ray sensitive Chinese hamster ovary cell line was isolated using a semi-automated procedure in which mutagenized CHO cells were allowed to form colonies on top of agar, x-irradiated, then photographed at two later times. Comparison of the photographs allowed the identification of colonies which displayed significant growth arrest. One of the colonies identified in this manner produced a stable, radiosensitive line. This cell line is normal in x-ray induced inhibition of DNA synthesis, and single- and double-strand break repair, and is moderately sensitive to ethyl methane sulfonate and UV light. The sensitive line performs only half as much x-ray-induced repair replication as the parental line and this deficiency is believed to be the primary cause of its radiosensitivity. The sensitive line produces significantly higher numbers of x-ray-induced chromosome and chromatid aberrations including chromatid aberrations following exposure during the G 1 phase of the cell cycle. The line is hypomutable compared to the parental line with x-ray exposure inducing only one-third as many 6-thioguanine resistant colonies

Characterization of recombinant human erythropoietin produced in Chinese hamster ovary cells

International Nuclear Information System (INIS)

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

1987-01-01

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 - and acrylamide but not by Cs + . 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

A Consensus Genome-scale Reconstruction of Chinese Hamster Ovary Cell Metabolism

KAUST Repository

Hefzi, Hooman

2016-11-23

Chinese hamster ovary (CHO) cells dominate biotherapeutic protein production and are widely used in mammalian cell line engineering research. To elucidate metabolic bottlenecks in protein production and to guide cell engineering and bioprocess optimization, we reconstructed the metabolic pathways in CHO and associated them with >1,700 genes in the Cricetulus griseus genome. The genome-scale metabolic model based on this reconstruction, iCHO1766, and cell-line-specific models for CHO-K1, CHO-S, and CHO-DG44 cells provide the biochemical basis of growth and recombinant protein production. The models accurately predict growth phenotypes and known auxotrophies in CHO cells. With the models, we quantify the protein synthesis capacity of CHO cells and demonstrate that common bioprocess treatments, such as histone deacetylase inhibitors, inefficiently increase product yield. However, our simulations show that the metabolic resources in CHO are more than three times more efficiently utilized for growth or recombinant protein synthesis following targeted efforts to engineer the CHO secretory pathway. This model will further accelerate CHO cell engineering and help optimize bioprocesses.

Effects of Body Mass Index on Lung Function Index of Chinese Population

Science.gov (United States)

Guo, Qiao; Ye, Jun; Yang, Jian; Zhu, Changan; Sheng, Lei; Zhang, Yongliang

2018-01-01

To study the effect of body mass index (BMI) on lung function indexes in Chinese population. A cross-sectional study was performed on 10, 592 participants. The linear relationship between lung function and BMI was evaluated by multivariate linear regression analysis, and the correlation between BMI and lung function was assessed by Pearson correlation analysis. Correlation analysis showed that BMI was positively related with the decreasing of forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and FEV1/FVC (P <0.05), the increasing of FVC% predicted value (FVC%pre) and FEV1% predicted value (FEV1%pre). These suggested that Chinese people can restrain the decline of lung function to prevent the occurrence and development of COPD by the control of BMI.

Amount of sister chromatid exchanges and survival of Chinese hamster V79-4 cells after irradiation with 0,7 MeV neutrons

International Nuclear Information System (INIS)

Lapidus, I.L.; Nasonova, E.A.

1987-01-01

The dependence of the survival and induction of sister chromatid exchanges (SCEs) in Chinese hamster V79-4 cells on the dose of γ-rays and neutrons with average energy 0.7 MeV has been analysed. The value of RBE for neutrons was 5.5. It has been shown that the number of SCE increased with the dose of γ-irradiation and no induction could be detected after neutron irradiation

Etoposide; colchicine; mitomycin C and cyclophosphamide tested in the in vitro mammalian cell micronucleus test (MNvit) in Chinese hamster lung (CHL) cells at Covance laboratories; Harrogate UK in support of OECD draft Test Guideline 487.

Science.gov (United States)

Fowler, Paul; Whitwell, James; Jeffrey, Laura; Young, Jamie; Smith, Katie; Kirkland, David

2010-10-29

The following genotoxic chemicals were tested in the in vitro micronucleus assay, at Covance Laboratories, Harrogate, UK in the Chinese hamster lung cell line CHL. Etoposide (a topoisomerase inhibitor), colchicine (an aneugen), mitomycin C (a DNA cross linking agent) and cyclophosphamide (an alkylating agent requiring metabolic activation) were treated with and without cytokinesis block (by addition of cytochalasin B). This work formed part of a collaborative evaluation of the toxicity measures recommended in the draft OECD Test Guideline 487 for the in vitro micronucleus test. The toxicity measures used, detecting both cytostasis and cell death, were relative population doubling, relative increase in cell counts and relative cell counts for treatments in the absence of cytokinesis block, and replication index or cytokinesis blocked proliferation index in the presence of cytokinesis block. All of the chemicals tested gave significant increases in the percentage of micronucleated cells with and without cytokinesis block at concentrations giving approximately 60% toxicity (cytostasis and cell death) or less by all of the toxicity measures used. The outcomes from this series of tests support the use of relative increase in cell counts and relative population doubling, as well as relative cell counts, as appropriate measures of cytotoxicity for the non-cytokinesis blocked in vitro micronucleus assay. Copyright © 2010 Elsevier B.V. All rights reserved.

Interphase death of dividing cells. Death rate of cultured Chinese hamster fibroblasts as a function of ph inside and outside cells

International Nuclear Information System (INIS)

Veksler, A.M.; Kublik, L.N.; Ehjdus, L.Kh.

1990-01-01

In studying interphase death (ID) of dividing cells from Chinese hamster fibroblast culture a differently directed relationship between ID rate and pH has been shown: the ID rate increases with pH increasing from 6.6 to 8.1 and decreases with pH from 5.0 to 6.6. The dependence is the same as that observed with lymphoid cells. With radiation doses increasing from 100 to 600 Gy and pH defined, the ID rate increases

The effect of purine phosphonomethoxyalkyl derivatives on DNA synthesis in Cho Chinese hamster cells

Energy Technology Data Exchange (ETDEWEB)

Stetina, R [Institute of Experimental Medicine, Laboratory of Developmental Toxicology, Academy of Sciences of Czech Republic, 51783 Olesnice v Orlickych horach (Czech Republic); Votruba, I; Holy, A; Merta, A [Institute of Organic Chemistry and Biochemistry, Academy of Sciences of Czech Republic (Czech Republic)

1994-12-31

The inhibition of incorporation of {sup 3}H-thymidine and the changes of the rate of nascent DNA chain elongation were investigated in Cho Chinese hamster cells treated with (S)-(3-hydroxy-2-phosphonomethoxypropyl) (HPMP) and N-(2-phosphonomethoxyethyl) (PME) derivatives of adenine (A), guanine (G) and 2,6-diaminopurine (DAP). No direct correlation was observed in PME and HPMP derivatives between cytotoxicity, inhibition of {sup 3}H-thymidine incorporation and inhibition of nascent DNA chain elongation. The highest cytotoxicity and inhibition of DNA synthesis were caused by PMEG. The limited extent of inhibition of DNA elongation was encountered in the case of HPMPG and HPMPA. With PMEA, weak inhibition of elongation of DNA was observed only after a prolonged exposure (6 h). None of the investigated drugs induced DNA breaks. (author) 4 figs., 23 refs.

Biophysical interpretation of the response of Chinese hamster cells to 24 keV neutrons

International Nuclear Information System (INIS)

Holt, P.D.

1988-01-01

The response of V79 Chinese hamster cells to a 24 keV neutron spectrum has been compared with data for the response of V79 cells to a range of higher neutron energies (up to 15 MeV). The linear energy transfer (LET) distributions of the neutron spectra were calculated and the expected responses of the cells to the different spectra were calculated using published track-segment data on the response of V79 cells to charged particles with various LET values. The response of the cells to 24 keV neutrons was predicted satisfactorily by the LET distribution, in spite of the fact that the maximum range of the recoil protons is only 0.5 μm. The response was not correctly predicted by the microdosimetric parameter y-bar D * evaluated in a 1 μm diameter sphere. (author)

Chinese hamster ovary cell mutants defective in heparan sulfate biosynthesis

International Nuclear Information System (INIS)

Bame, K.J.; Kiser, C.S.; Esko, J.D.

1987-01-01

The authors have isolated Chinese hamster ovary cell mutants defective in proteoglycan synthesis by radiographic screening for cells unable to incorporate 35 SO 4 into acid-precipitable material. Some mutants did not incorporate 35 SO 4 into acid-precipitable material, whereas others incorporated about 3-fold less radioactivity. HPLC anion exchange chromatographic analysis of radiolabelled glycosaminoglycans isolated from these mutants revealed many are defective in heparan sulfate biosynthesis. Mutants 803 and 677 do not synthesize heparan sulfate, although they produce chondroitin sulfate: strain 803 makes chondroitin sulfate normally, whereas 677 overaccumulates chondroitin sulfate by a factor of three. These mutants fall into the same complementation group, suggesting that the mutations are allelic. A second group of heparan sulfate biosynthetic mutants, consisting of cell lines 625, 668 and 679, produce undersulfated heparan sulfate and normal chondroitin sulfate. Treatment of the chains with nitrous acid should determine the position of the sulfate groups along the chain. These mutants may define a complementation group that is defective in the enzymes which modify the heparan sulfate chain. To increase the authors repertoire of heparan sulfate mutants, they are presently developing an in situ enzyme assay to screen colonies replica plated on filter discs for sulfotransferase defects

Isolation of cell cycle-dependent gamma ray-sensitive Chinese hamster ovary cell

International Nuclear Information System (INIS)

Stamato, T.D.; Weinstein, R.; Giaccia, A.; Mackenzie, L.

1983-01-01

A technique for the isolation of gamma ray-sensitive Chinese hamster ovary (CHO) cell mutants is described, which uses nylon cloth replica plating and photography with dark-field illumination to directly monitor colonies for growth after gamma irradiation. Two gamma ray-sensitive mutants were isolated using this method. One of these cells (XR-1) had a two-slope survival curve: an initial steep slope and then a flattening of the curve at about 10% survival. Subsequently, it was found that this cell is sensitive to gamma irradiation in G1, early S, and late G2 phases of the cell cycle, whereas in the resistant phase (late S phase) its survival approaches that of the parental cells. The D37 in the sensitive G1 period is approximately 30 rads, compared with 300 rads of the parental cell. This mutant cell is also sensitive to killing by the DNA breaking agent, bleomycin, but is relatively insensitive to UV light and ethyl methane sulfonate, suggesting that the defect is specific for agents that produce DNA strand breakage

Structural changes in plasma membranes prepared from irradiated Chinese hamster V79 cells as revealed by Raman spectroscopy

International Nuclear Information System (INIS)

Verma, S.P.; Sonwalkar, N.

1991-01-01

The effect of gamma irradiation on the integrity of plasma membranes isolated from Chinese hamster V79 cells was investigated by Raman spectroscopy. Plasma membranes of control V79 cells show transitions between -10 and 5 degree C (low-temperature transition), 10 and 22 degree C (middle-temperature transition), and 32 and 40 degree C (high-temperature transition). Irradiation (5 Gy) alters these transitions markedly. First, the low-temperature transition shifts to higher temperature (onset and completion temperatures 4 and 14 degree C). Second, the middle-temperature transition shifts up to the range of about 20-32 degree C, but the width remains unchanged. Third, the higher temperature transition broadens markedly and shifts to the range of about 15-40 degree C. Protein secondary structure as determined by least-squares analysis of the amide I bands shows 36% total helix, 55% total beta-strand, and 9% turn plus undefined for control plasma membrane proteins. Plasma membrane proteins of irradiated V79 cells show an increase in total helix (40 and 45% at 5 and 10 Gy, respectively) and a decrease in the total beta-strand (48 and 44% at 5 and 10 Gy, respectively) structures. The qualitative analysis of the Raman features of plasma membranes and model compounds in the 1600 cm-1 region, assigned to tyrosine groups, revealed that irradiation alters the microenvironment of these groups. We conclude that the radiation dose used in the survival range of Chinese hamster V79 cells can cause damage to plasma membrane proteins without detectable lipid peroxidation, and that the altered proteins react differently with lipids, yielding a shift in the thermal transition properties

Influence of irradiation at different stages of mitotic cycle upon production of sister chromatid exchanges in cultured Chinese hamster cells

International Nuclear Information System (INIS)

Antoshina, M.M.; Poryadkova, N.A.; Luchnik, N.V.

1982-01-01

Frequency of sister chromatid exchanges (SCE) and microexchanges in Chinese hamster cells has been studied by means of the method of differential staining of chromatids on irradiation at different stages of the mitotic cycle. It is shown that the irradiation enhances frequency of SCE and microexchanges if it is carried out before the end of DNA replication synthesis. Comparison of frequency depenedence of radiation-induced microexchanges and SCE at different stages of the mitotic cycle results in the conclusion that the microexchanges are none other than small SCE

Culture conditions affecting the survival response of Chinese hamster ovary cells treated by hyperthermia

International Nuclear Information System (INIS)

Highfield, D.P.; Holahan, E.V.; Dewey, W.C.

1982-01-01

Using lethally irradiated feeder cells to control cell population densities, researchers investigated the survival of Chinese hamster ovary cells heated between 42.2 and 45.5 degrees C. Test cells were plated into T25 flasks with or without feeder cells, incubated 2 hours at 37 degrees C, and then given various heat treatments. Under all heating conditions, survival increased in those flasks containing feeder cells. Increased survival (by as much as a factor of 100 for cells heated at 42.4 degrees C for 6-10 hr) was most apparent when cells were heated to thermotolerance. By adjustment of test and feeder cell numbers, survival increased as density increased; however, maximum survival followed a transition period that occurred between the plating of 1 X 10(4) and 6 X 10(4) cells. Experimental artifacts due to improper control of cell density was demonstrated

Permeabilization of ultraviolet-irradiated chinese hamster cells with polyethylene glycol and introduction of ultraviolet endonuclease from Micrococcus luteus

International Nuclear Information System (INIS)

Yarosh, D.B.; Setlow, R.B.

1981-01-01

Chinese hamster V-79 cells were made permeable by treatment with polyethylene glycol and then incubated with a Micrococcus luteus extract containing ultraviolet-specific endonuclease activity. This treatment introduced nicks in irradiated, but not in unirradiated, deoxyribonucleic acid. The nicks remained open for at least 3 h; there was no loss of endonuclease-sensitive sites, and no excision of dimers as measured by chromatography was detected. In addition, there was no increase in ultraviolet resistance in treated cells. This suggests that the absence of a significant amount of excision repair in rodent cells is due to the lack of both incision and excision capacity

Gene mutations, chromosome aberrations and survival after X-ray irradiation of cultured Chinese hamster cells at cysteamine protection

International Nuclear Information System (INIS)

Elisova, I.V.; Feoktistova, I.P.

1983-01-01

The culture of Chinese hamster cells (clone 431) has been used to study cysteamine action on mutagenous effect of X-rays, determined by the induction of resistance of gene mutations to 6-thioguanine and chromosomal abberations, as well as on the reproductive form of death of irradiated cells. Dose--- effect curves are obtained under conditions of irradiation with and without protector. The factor of dose alteration is 2.0 for chromosomal aberrations and cell survival, and 2.8 for gene mutations. It is sUpposed that cysteamine affects the general mechanisms, which take part in the realis zation of injuries that bring about gene mutations, chromosomal aberrations and cell lethality

Transmission and adaptation of chronic wasting disease to hamsters and transgenic mice: evidence for strains.

Science.gov (United States)

Raymond, Gregory J; Raymond, Lynne D; Meade-White, Kimberly D; Hughson, Andrew G; Favara, Cynthia; Gardner, Donald; Williams, Elizabeth S; Miller, Michael W; Race, Richard E; Caughey, Byron

2007-04-01

In vitro screening using the cell-free prion protein conversion system indicated that certain rodents may be susceptible to chronic wasting disease (CWD). Therefore, CWD isolates from mule deer, white-tailed deer, and elk were inoculated intracerebrally into various rodent species to assess the rodents' susceptibility and to develop new rodent models of CWD. The species inoculated were Syrian golden, Djungarian, Chinese, Siberian, and Armenian hamsters, transgenic mice expressing the Syrian golden hamster prion protein, and RML Swiss and C57BL10 wild-type mice. The transgenic mice and the Syrian golden, Chinese, Siberian, and Armenian hamsters had limited susceptibility to certain of the CWD inocula, as evidenced by incomplete attack rates and long incubation periods. For serial passages of CWD isolates in Syrian golden hamsters, incubation periods rapidly stabilized, with isolates having either short (85 to 89 days) or long (408 to 544 days) mean incubation periods and distinct neuropathological patterns. In contrast, wild-type mouse strains and Djungarian hamsters were not susceptible to CWD. These results show that CWD can be transmitted and adapted to some species of rodents and suggest that the cervid-derived CWD inocula may have contained or diverged into at least two distinct transmissible spongiform encephalopathy strains.

Amino acid analysis and cell cycle dependent phosphorylation of an H1-like, butyrate-enhanced protein (BEP; H10; IP25) from Chinese hamster cells

International Nuclear Information System (INIS)

D'Anna, J.A.; Gurley, L.R.; Becker, R.R.; Barham, S.S.; Tobey, R.A.; Walters, R.A.

1980-01-01

A fraction enriched in the butyrate-enhanced protein (BEP) has been isolated from Chinese hamster (line CHO) cells by perchloric acid extraction and Bio-Rex 70 chromatography. Amino acid analyses indicate that the composition of BEP resembles that of CHO H1; however, BEP contains 11% less alanine than H1, and, in contrast to H1, BEP contains methionine. Treatment of BEP with cyanogen bromide results in the cleavage of a small fragment of approx. 20 amino acids so that the large fragment seen in sodium dodecyl sulfate-acrylamide gels has a molecular weight of approx. 20,000. Radiolabeling and electrophoresis indicate that BEP is phosphorylated in a cell cycle dependent fashion. These data suggest that (1) BEP is a specialized histone of the H1 class and (2) BEP is the species equivalent of calf lung histone H1 0 , rat H1 0 , and IP 25 , a protein enhanced in differentiated Friend erythroleukemia cells. The data also indicate that putative HMG1 and HMG2 proteins do not undergo the extensive cell cycle dependent phosphorylations measured for histone H1 and BEP

Gene amplification in Chinese hamster embryo cells by the decay of incorporated iodine-125

International Nuclear Information System (INIS)

Luecke-Huhle, Christine; Ehrfeld, Angelika; Rau, Waltraud

1988-01-01

Simian Virus 40-transformed Chinese hamster embryo cells (Co631) contain 5 viral copies integrated per cell genome. These SV40 sequences were used as an endogenous indicator gene to study response of mammalian cells to radiation at gene level. Cells were internally irradiated by Auger electrons emitted by Iodine-125 which was incorporated in cell DNA in form of 5-[ 125 I] iododeoxyuridine ( 125 IdU). An increase in gene copy number was measured using dispersed cell blotting and Southern analysis in combination with highly sensitive DNA hybridization. A 13-fold amplification of the SV40 sequences and a 2-fold amplification of two cellular oncogenes of the ras family were found. Other cellular genes, like the α-actin gene, are not amplified and no variation in gene copy number was observed after incubation of cells with cold IdU. Thus, specific gene amplification seems to be the consequence of radiation-induced DNA damage and the resulting cell cycle arrest. (author)

Caffeine-enhanced survival of radiation-sensitive, repair-deficient Chinese hamster cells

International Nuclear Information System (INIS)

Utsumi, H.; Elkind, M.M.

1983-01-01

A clone of V79 Chinese hamster cells (V79-AL162/S-10) with unique properties has been isolated after a challenge of parental cells (V79-AL162) with 1 mM ouabain. Compared with parental cells, or with other clones isolated after the ouabain challenge, these cells form smaller colonies, are more sensitive to both x rays and fission-spectrum neutrons, and respond atypically to a postirradiation treatment with caffeine. Their enhanced response to x rays results mainly from a large reduction in the shoulder of their survival curve, probably because in late S phase, the most resistant phase in the cell cycle, the survival curve of these cells has a reduced shoulder width. Caffeine, and to a lesser extent theophylline, added to the colony-forming medium immediately after exposure appreciably increases the width of the shoulder of these sensitive cells, whereas caffeine has the opposite effect on the response of normal V79 cells. Thus the unique response of the V79-AL162/S-10 cells to a radiation posttreatment with caffeine (increased survival) results from a net increase in their ability to repair damage that is otherwise lethal; caffeine treatment ordinarly prevents normal V79 cells from repairing damage that is only potentially lethal

Mutagenic and epigenetic influence of caffeine on the frequencies of UV-induced ouabain-resistant Chinese hamster cells

International Nuclear Information System (INIS)

Chang, Chia-Cheng; Philipps, C.; Trosko, J.E.; Hart, R.W.

1977-01-01

Caffeine, given as a post-treatment to UV-irradiated Chinese hamster cells in vitro, modified the frequency of induced mutations at the ouabain resistance locus. Mutation frequencies were increased when caffeine was added only for the DNA repair and mutation fixation period. When caffeine was added after the DNA repair and mutation fixation period, or immediately after DNA damage and for the entire repair and selection period, mutation frequencies were reduced. A hypothesis, given to explain both results, is that caffeine, by blocking a constitutive 'error-free' postreplication repair process, allows an 'error-prone' DNA repair process to produce many mutations. Moreover, caffeine, possibly by modifying C-AMP metabolism, causes a repression of induced mutations which, in effect, explains its anti-mutagenic and anti-carcinogenic properties

Chromosome studies on bone marrow cells of chinese hamsters fed a radiosterilized diet

International Nuclear Information System (INIS)

Renner, H.W.

1977-01-01

Metaphase preparations of chromosomes from bone marrow cells of Chinese hamsters were examined for mutagenic effects following the feeding of a radiosterilized diet. No increase in the incidence of structural chromosomal aberrations was observed. As far as numerical aberrations were concerned, the proportion of cells with polyploidy increased to between 4 to 5 times the control level, irrespective of the moisture content of the diet. This polyploidy effect occurred very early, being detectable within 24 h, if the diet fed had been irradiated with an absorbed dose of 4.5x10 6 rad. The incidence of polyploidy remained below 0.5%, however, nor did it rise with higher radiation doses. When the feeding of the irradiated diet was stopped, the proportion of polyploid cells returned to the control level within a maximum of 6 weeks. If the diet was stored (initially) for 6 weeks following irradiation before being fed to the animals no increase in the number of polyploid cells was noted. These results are not interpreted as a mutagenic effect of the irradiated diet. (author)

Effects of proliferation on the decay of thermotolerance in Chinese hamster cells.

Science.gov (United States)

Armour, E P; Li, G C; Hahn, G M

1985-09-01

Development and decay of thermotolerance were observed in Chinese hamster HA-1 cells. The thermotolerance kinetics of exponentially growing and fed plateau-phase cells were compared. Following a 10-min heat exposure at 45 degrees C, cells in both growth states had similar rates of development of tolerance to a subsequent 45-min exposure at 45 degrees C. This thermotolerant state started to decay between 12 and 24 hr after the initial heat exposure. The decay appeared to initiate slightly sooner in the exponentially growing cells when compared to the fed plateau-phase cells. During the decay phase, the rate of thermotolerance decay was similar in the two growth conditions. In other experiments, cells were induced to divide at a slower rate by chronic growth (3 months) in a low concentration of fetal calf serum. Under these low serum conditions cells became more sensitive to heat and the rate of decay of thermotolerance remained the same for exponentially growing cells. Plateau-phase cells were also more sensitive, but thermotolerance decayed more rapidly in these cells. Although dramatic cell cycle perturbations were seen in the exponentially growing cells, these changes appeared not to be related to thermotolerance kinetics.

Icotinib: activity and clinical application in Chinese patients with lung cancer.

Science.gov (United States)

Guan, Yong-Song; He, Qing; Li, Mei

2014-04-01

Icotinib (BPI-2009H, Conmana) is a novel oral quinazoline compound that has proven survival benefit in Chinese patients with lung cancer, for which several therapies are currently available often with unsatisfactory results. Icotinib is the first self-developed small molecular drug in China for targeted therapy of lung cancer. The authors' experience in the clinical application of icotinib is reviewed in combination with related publications in the literature. Antitumor activities were observed in non-small-cell lung cancer and others in several recent studies. On 7 June 2011, icotinib was approved by the State Food and Drug Administration of China for the treatment of local advanced or metastatic non-small-cell lung cancer based on the results of a nationwide, of 27 centers, randomized, double-blind, double-modulated, parallel-controlled, Phase III trial with single agent icotinib in lung cancer patients after failure of chemotherapy. Icotinib is a generic drug. Compared to the other two commercially available EGFR tyrosine kinase inhibitors, gefitinib and erlotinib, icotinib is similar to them in chemical structure, mechanism of activity and therapeutic effects but less expensive. Better safety as well as a wider therapeutic window has also been proven in several Chinese studies. Future studies on cost effectiveness are warranted.

Enhancement of postreplication repair in ultraviolet-light-irradiated Chinese hamster cells by irradiation in G2 or s-phase

International Nuclear Information System (INIS)

D'Ambrosio, S.M.; Aebersold, P.M.; Setlow, R.B.

1978-01-01

Postreplication repair in synchronous Chinese hamster cells was determined after split doses of ultraviolet (uv) radiation. Repair was enhanced by irradiation of cells in G 2 or S-phase with a small dose of uv radiation at least 1.5 h before a three-fold larger dose of uv. There was significantly greater enhancement when the first dose was given in G 2 than when it was given in the S-phase 0.5 to 1.5 h before the test dose. These data indicate that enhancement of postreplication repair does not require active DNA replication and qualitatively is independent of when in the cell cycle the cells are irradiated

Ultraviolet light induction of diphtheria toxin-resistant mutations in normal and DNA repair-deficient human and Chinese hamster fibroblasts

International Nuclear Information System (INIS)

Trosko, J.E.; Schultz, R.S.; Chang, C.C.; Glover, T.

1980-01-01

The role on unrepaired DNA lesions in the production of mutations is suspected of contributing to the initiation phase of carcinogenesis. Since the molecular basis of mutagenesis is not understood in eukaryotic cells, development of new genetic markers for quantitative in vitro measurement of mutations for mammalian cells is needed. Furthermore, mammalian cells, genetically deficient for various DNA repair enzymes, will be needed to study the role of unrepaired DNA lesions in mutagenesis. The results in this report relate to preliminary attempts to characterize the diphtheria toxin resistance marker as a useful quantitative genetic marker in human cells and to isolate and characterize various DNA repair-deficient Chinese hamster cells

Differing sensitivity to fluorescent light in Chinese hamster cells containing equally incorporated quantities of BUdR versus IUdR

International Nuclear Information System (INIS)

Mitchell, J.B.; Morstyn, G.; Russo, A.; Kinsella, T.J.; Fornace, A. Jr.; McPherson, S.; Glatstein, E.

1984-01-01

Chinese hamster V79 cells that had incorporated approximately equal levels of either BUdR or IUdR into their DNA were found to be equal sensitizers to x rays. However, BUdR-substituted cells were much more sensitive to fluorescent light than IUdR-substituted cells, both on a cell survival basis and by the initial number of single strand DNA breaks induced. Since a major toxicity to the use of BUdR clinically has been light-induced skin rash, these data indicate that the use of IUdR clinically might cause less untoward toxicity but yet provide the same radiosensitization as BUdR

Permeability changes and incorporation of labelled thymidine into DNA and whole cells of the fibroblast culture of Chinese hamsters affected by MEA and low temperature

International Nuclear Information System (INIS)

Ermekova, V.M.; Kondakova, N.V.; Levitman, M.Kh.; Saugabaeva, K.M.; Ehjdus, L.Kh.

1976-01-01

Action of MEA and low temperature (20degC) on the incorporation of labelled thymidine into DNA and whole cells of the fibroblast culture of chinese hamsters has been studied. It has been found that each of the above-mentioned factors equally decreases the label uptake into the cell and DNA. It is concluded that MEA and low temperature do not substantially influence the rate of DNA synthesis

Lack of specificity of chromosome breaks resulting from radiation-induced genomic instability in Chinese hamster cells

International Nuclear Information System (INIS)

Trott, K.-R.; Teibe, A.

1998-01-01

In V79 Chinese hamster cells, radiation-induced genomic instability results in a persistently increased frequency of micronuclei, dicentric chromosomes and apoptosis and in decreased colony-forming ability. These manifestations of radiation-induced genomic instability may be attributed to an increased rate of chromosome breakage events many generations after irradiation. This chromosomal instability does not seem to be a property which has been inflicted on individual chromosomes at the time of irradiation. Rather, it appears to be secondary to an increased level of non-specific clastogenic factors in the progeny of most if not all irradiated cells. This conclusion is drawn from the observations presented here, that all the chromosomes in surviving V79 cells are involved in the formation of dicentric chromosome aberrations 1 or 2 weeks after irradiation with about equal probability if corrections are made for chromosome length. (orig.)

N-ethylmaleimide sensitization of x-irradiated hypoxic Chinese hamster cells

International Nuclear Information System (INIS)

Kimler, B.F.; Sinclair, W.K.; Elkind, M.M.

1977-01-01

Chinese hamster cells were x irradiated either aerobically or hypoxically, after flushing with nitrogen plus carbon dioxide. In agreement with earlier data, for asynchronous cells, the oxygen enhancement ratio (OER) was approximately three. If the sulfhydryl-binding agent N-ethylmaleimide (NEM) was present during or immediately after irradiation, the principal effect was a pronounced decrease in the extrapolation number of the survival curve of NEM-treated cells compared to nontreated cells. This was observed with hypoxic as well as aerobic cells and the OER for NEM-treated cells was also about three. For NEM treatments which were essentially nontoxic, NEM acts synergistically with X rays, suggestive of an inhibition by NEM of a cell's ability to repair sublethal damage. For synchronous cells obtained by mitotic selection, a result consistent with the above was obtained; a dose three times as large was necessary to reduce survival to the same level for hypoxic cells as for aerobic cells, whether or not the cells were treated with NEM. Thus the OER was independent of NEM treatment throughout the cell cycle, with the possible exception of mitosis which could not be studied with the methods used. It is concluded that the action of NEM at low concentrations (0.75 μM) is largely independent of oxygen tension. Oxygen acts to produce more damage per unit dose in the cell while NEM sensitizes apparently by preventing the repair of sublethal damage

Development of the Fibulin-3 protein therapeutics of non small cell lung cancer stem cells

Energy Technology Data Exchange (ETDEWEB)

Kim, In Gyu; Kim, Kugchan; Jung, Il Lae; Kim, Seo Yeon; Choi, Su Im; Lee, Jae Ha

2013-09-15

This study focuses on developing an efficient bioprocess for large-scale production of fibulin-3 using Chinese Hamster Ovary cell expression system and evaluating its therapeutic potential for the treatment of cancer. The specific aims are as follows: Isolation and establishment of CSCs using FACS based on cell surface markers and high ALDH1 activity. Identification and characterization of lung cancer stem cells that acquire features of CSC upon exposure to ionizing radiation. Evaluation of the fibulin-3 effects on the stem traits and signaling pathways required for the generation and maintenance of CSCs. In vivo validation of fivulin-3 for tumor prognosis and therapeutic efficacy against lung cancer using animal model.

Effect of dihydroxyanthraquinone (DHAQ) and radiation on the survival of cultured Chinese hamster ovary cells

International Nuclear Information System (INIS)

Kimler, B.F.

1983-01-01

Dihydroxyanthraquinone (DHAQ) is currently being tested as a cancer chemotherapeutic agent because of its structural similarity to Adriamycin (ADR) and other DNA-intercalating antibiotics. The interaction of DHAQ and ionizing radiation on the induction of cell lethality was investigated in Chinese hamster ovary cells in culture. In asynchronous populations of cells, DHAQ produced a slight enhancement of radiation-induced cell lethality as evidenced by changes in both shoulder and slope of the radiation dose-survival curves. However, DHAQ had no effect on either the extent or time course of recovery from sublethal radiation damage. In synchronous populations of cells treated at various times before or after selection in mitosis, the combination of DHAQ and radiation produced greater cell killing than that predicted based on simple additivity of effect, with a decided enhancement for cells treated during S phase. These results indicate that DHAQ is similar to other DNA-intercalating antibiotics in regard to the interaction with ionizing radiation to produce cell lethality

Quantification and analysis of reverse mutations at the hgprt locus in Chinese hamster ovary cells

Energy Technology Data Exchange (ETDEWEB)

Fuscoe, J.C.; O' Neill, J.P.; Machanoff, R.; Hsie, A.W.

1982-01-01

An assay is described for the quantification of reverse mutations at the hypoxanthine-guanine phosphoribosyltransferase (hgprt) locus in Chinese hamster ovary cells utilizing the selective agent L-azaserine (AS). Conditions are defined in terms of optimal AS concentration, cell density, and phenotypic expression time. After treatment, replicate cultures of 10/sup 6/ cells are allowed a 48-h phenotypic expression time in 100-mm plates. AS (10..mu..M) is then added directly to the growing culture and AS-resistant (AS/sup r/) cells form visible colonies. This assay is used to quantify ICR-191-, ICR-170-, and N-ethyl-N-nitrosourea-induced reversion of independently isolated HGPRT/sup -/ clones. The AS/sup r/ phenotype is characterized both physiologically and biochemically. All AS/sup r/ clones isolated are stably resistant to AS and aminopterin but sensitive to 6-thioguanine. They also have re-expressed HGPRT enzyme. In addition, several revertants are shown to contain altered HGPRT.

Mutagenicity of 8-methoxypsoralen and long-wave ultraviolet irradiation in V-79 Chinese hamster cells

International Nuclear Information System (INIS)

Burger, P.M.; Simons, J.W.I.M.

1979-01-01

The effect of 8-methoxypsoralen (8-MOP) and long-wave ultraviolet irradiation (UVA) on cell killing and mutation induction was studied in V-79 Chinese hamster cells. No effect was observed after treatment with 8-MOP alone (50 μg/ml, 4 h), UVA alone (9000 J/m 2 ), or 8-MOP metobolized by rat-liver microsomes. Combined treatment with 8-MOP and UVA induced both cell killing and mutation. This was also observed under conditins approaching patient treatment with PUVA photochemotherapy with respect to the concentration of 8-MOP in the skin and the amount of UVA received by the epidermal cells. A simple relation proved to apply for mutation induction under different treatment conditions: 5.5 X 10 -8 per J/m 2 per μg 8-MOP/ml. On this basis the mutation induction in dividing cells per session of PUVA-photochemotherapy amounts to 12.4 X 10 -5 , which is probably an over-estimation. (Auth.)

Effects of 3-Deoxyadenosine (Cordycepin) on the repair of X-ray-induced DNA single- and double-strand breaks in chinese hamster V79 cells

International Nuclear Information System (INIS)

Hiraoka, Wakako; Kuwabara, Mikinori; Sato, Fumiaki

1990-01-01

The ability of cordycepin to inhibit the repair of DNA strand breaks was examined with X-irradiated Chinese hamster V79 cells in log-phase culture. A filter elution technique revealed that 70 μM cordycepin did not inhibit the repair of single-strand breaks but inhibited the repair of double-strand breaks. These findings confirmed the fact that the increase in the lethality of cordycepin in X-irradiated cultured mammalian cells was attributable to unrepaired DNA double-strand breaks. (author)

The influence of continuous γ-irradiation at decreasing dose-rate on the survival rote and induction of gene mutations in cultured Chinese hamster cells

International Nuclear Information System (INIS)

Feoktistova, T.P.; Elisova, E.V.; Stavrakova, N.M.

1991-01-01

Continuous γ-irradiation at decreasing dose-rate was shown to be less effective than acute exposure with regard to the lethal effect and frequency of mutations of resistance to 6-thioguanine in cultured Chinese hamster cells. The cell population subjected to continuons irradiation was d more radioresistant than the intact one. Lethal and genetic effects of continuous irradiation at decreasing dose-rate were mainly determined by the contribution of the radiation dose received during the first 24 h of exposure

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)

Millar, B.C.; Jinks, S.

1981-01-01

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)

Protective action of DNA preparations on the survival of cells and yield of 8-azaguanine resistant mutations in X-irradiated cell culture of chinese hamsters

International Nuclear Information System (INIS)

Kuznetsova, N.N.; Feoktistova, T.P.

1976-01-01

A DNA preparation (molecular weight 19.6-21.0x1O 6 daltons) administered to cell culture of Chinese hamsters in concentrations of 100 to 122 μg/ml 60 minutes before and in the course of 3 days after X-irradiation (600 R) decreased the lethality of irradiated cells and reduced induction of 8-azaguanine resistant genic mutations. DNA preparations with the concentrations under study had no toxic action on cells and were not mutagenous

[Study on characteristics of pharmacological effects of traditional Chinese medicines distributing along lung meridian based on medicinal property combination].

Science.gov (United States)

Gu, Hao; Zhang, Yan-Ling; Wang, Yun; Qiao, Yan-Jiang

2014-07-01

Medicinal properties are the basic attribute of traditional Chinese medicines (TCM), while the medicinal property theory is the core theoretical foundation of TCM formula combination. In this particle, authors studied the characteristics of pharmacological effects of property combination of traditional Chinese medicines distributing along meridians, with the aim to introduce the medicinal property combination regularity into the design and optimization process of compound TCMs, and bring the medicinal property theory into full play in guiding the formula combination. In this paper, TCMs distributing along "the lung meridian" was taken for example. The medicinal property combinations of TCMs distributing along "the lung meridian" recorded in Pharmacopeia (2010) was collected and processed. Besides, Chinese journal full-text database (CNKI) was used to collect all of pharmacological study literatures concerning the above TCMs that have been published since 1980. The pharmacological information was also supplemented by reference to Science of Chinese Materia Medica and Clinical Science of Chinese Materia Medica. TCMs distributing along the lung meridian with different properties and tastes showed significant differences in pharmacological effects. For example, mild-sweet-lung medicines could lower blood sugar levels, decrease anoxia and enhance immunity; Mild-bitter-lung medicines showed anti-bacterial, anti-hypertension, anti-oxidation effects; Hot-sweet-lung medicines showed antibechic and anti-bacterial effects. And Hot-bitter-lung medicines showed phlegm eliminating and anti-inflammatory effects. Meanwhile, TCMs distributing along the lung meridian had similar pharmacological characteristics, such as anti-bacterial and anti-inflammatory effects, which is consistent with lung's feature in susceptibility to exogenous pathogenic factors. In this study, authors discovered pharmacological characteristics of different TCMs distributing along the lung meridian, which

Transgenic Chinese hamster V79 cell lines which exhibit variable levels of gpt mutagenesis

International Nuclear Information System (INIS)

Klein, C.B.; Rossman, T.G.

1990-01-01

The Escherichia coli gpt gene coding for xanthine-guanine phosphoribosyl transferase has been stably transfected into HPRT - Chinese hamster V79 cells. Several gpt - cell lines have been established, which retain the sequence(s) even after long-term culture without selection for gpt. While spontaneous mutagenesis to gpt - occurs rather frequently for most cell lines, it cannot be correlated with either the number of plasmid integration sites or deletion of the plasmid sequence(s). One transgenic cell line (g12), which continuously maintains a low spontaneous mutation frequency was used in comparative mutagenesis studies with wild-type V79 cells (gpt vs. hprt). Alkylating agents such as N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and β-propiolactone (BPL) are shown to be equally toxic and mutagenic in both g12 and V79 cells. UV and X-rays are also equally toxic to both cell lines. The data presented here suggests that g12 cells may be useful to study mammalian mutagenesis by agents which yield limited response at the hprt locus

Expression of UV-irradiated adenovirus in normal and UV-sensitive Chinese hamster ovary cells

International Nuclear Information System (INIS)

Rainbow, A.J.

1985-01-01

The chinese hamster ovary (CHO) cell mutants UV-20, UV-24, and UV-41 are abnormally sensitive to UV and harbour various defects lin their ability to repair cellular DNA. This study has examined the expression of UV-irradiated AD2 in these cells. HCR of UV-irradiated Ad2, as measured by viral structural antigen (Vag) formation or progeny production, was found to be similar for the normal and the UV-sensitive CHO strains. UV-irradiation of Ad2 (1200 J/m/sup 2/) resulted in a delay of Vag expression of 18 hours in normal human fibroblasts, which is thought to reflect the time required for removal of UV-induced lesions from the DNA before viral DNA synthesis can proceed. However, a similar UV-irradiation of Ad2 did not result in a delay of Vag expression for infection of CHO cells, suggesting that UV-induced lesions in Ad2 DNA do not inhibit its replication in CHO cells. These results indicate a fundamental difference in the processing of UV-irradiated AD2-DNA in CHO as compared to human cells

Evidence for multiple repair pathways of double-strand DNA breaks in Chinese hamster cells

International Nuclear Information System (INIS)

Giaccia, A.J.; Weistein, R.; Stamato, T.D.; Roosa, R.

1984-01-01

XR-1 is a mutant of the Chinese hamster cell (CHO-K1) which is abnormally sensitive to killing by gamma rays in G/sub 1/ (D37 = 27 rads vs. 318 for parent) and early S phases of the cell cycle but has near normal resistance in late S and early G/sub 2/ (Somatic Cell Genetics, 9:165-173, 1983). Complementation studies between XR-1 and its parent indicate that this sensitivity to gamma rays is a recessive phenotype. Both the XR-1 and its parent cell are able to repair single strand DNA breaks. However, in comparison to its parental cell, the XR-1 cell is markedly deficient in the repair of double strand DNA breaks introduced by gamma irradiation during the sensitive G/sub 1/-early S period, while in the late S-G/sub 2/ resistant period the repair is similar in both cells. This correlation suggests that an unrepaired double strand DNA break is the lethal lesion and that at least two pathways for the repair of these lesions exist in mammalian cells

Effects of laser uv-microirradiation (lambda=2573 A) on proliferation of Chinese hamster cells

International Nuclear Information System (INIS)

Cremer, C.; Cremer, T.; Zorn, C.; Schoeller, L.

1976-01-01

A laser uv-microbeam with a wavelength of 2573 A having a minimum spot diameter of approximately 0.5 μm was used to microirradiate interphase cells of a V-79 subline of Chinese hamster cells. The incident energy necessary to induce a significant decrease of proliferation was 30 to 60 times larger after microirradiation of cytoplasm as compared with microirradiation of nucleoplasm. The mean value of relative cell numbers 40 hr after irradiation as a function of incident energy did not differ whether the cells were microirradiated lying singly or together in small groups. Analysis of individual growth curves of singly lying cells microirradiated in the nucleoplasm with the same energy showed heterogeneous reactions. The incident energy per cell compatible with proliferation of about 50 percent of the cells after microirradiation of nucleoplasm was approximately 2 x 10 -3 ergs. From this value it is suggested that the energy density within the focus was in the region of several thousand ergs per square millimeter. Photochemical effects are thought to be the cause of growth disturbance, while thermal effects are excluded

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

Energy Technology Data Exchange (ETDEWEB)

Gillett, N A; Guilmette, R A; Eidson, A F; Griffith, W C; Brooks, A L

1988-12-01

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 {sup 239}Pu 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)

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

International Nuclear Information System (INIS)

Gillett, N.A.; Guilmette, R.A.; Eidson, A.F.; Griffith, W.C.; Brooks, A.L.

1988-01-01

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 239 Pu 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)

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

International Nuclear Information System (INIS)

Saito, Tsutomu

1983-01-01

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

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

International Nuclear Information System (INIS)

Saito, Tsutomu; Shimada, Yuji; Kamata, Rikisaburo

1989-01-01

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 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)

Expression of a human gene for polyamine transport in Chinese-hamster ovary cells.

Science.gov (United States)

Byers, T L; Wechter, R; Nuttall, M E; Pegg, A E

1989-01-01

A molecular-genetic approach towards isolating mammalian polyamine-transport genes and their encoded proteins was devised involving the production of Chinese-hamster ovary (CHO) cells expressing a human polyamine-transport protein. CHO cells and a polyamine-transport-deficient CHO mutant cell line (CHOMG) were equally sensitive to the antiproliferative effects of alpha-difluoromethylornithine (DFMO), which blocked endogenous polyamine synthesis. Exposure to exogenous polyamines increased intracellular polyamine levels and reversed this DFMO-induced cytostasis in the CHO cells, but not in the CHOMG cells. CHOMG cells were therefore transfected with human DNA (isolated from HT-29 colon carcinoma cells) and cells expressing the human polyamine-transport system were identified by the ability of these cells to grow in a medium containing DFMO and polyamines. A number of different positive clones were identified and shown to have the capacity for polyamine uptake and an increased sensitivity to the toxic effects of the polyamine analogue methylglyoxal bis(guanylhydrazone). Differences in these properties between the clones are consistent with a multiplicity of polyamine-transport systems. Some clones also showed a change in growth characteristics, which may indicate a relationship between genes involved in the polyamine-transport system and in cell proliferation. PMID:2512913

Inhibition of DNA chain elongation in Chinese hamster cells by damage localized behind the replication fork

Energy Technology Data Exchange (ETDEWEB)

Ben-Hur, E [Israel Atomic Energy Commission, Beersheba. Nuclear Research Center-Negev; Hagan, M P [Armed Forces Radiobiology Research Inst., Bethesda, MD (USA)

1984-05-01

Chinese hamster fibroblasts were pulse labelled with 5-bromodeoxyuridine and exposed at time intervals (Tsub(i)) to near-ultraviolet (U.V.A.) light in the presence of a bisbenzimidazole derivative (Hoechst 33342). The sensitivity of the cells in terms of colony forming ability fluctuated depending on Tsub(i). Inhibition of DNA synthesis also depended on Tsub(i) and was maximal when Tsub(i)=O. Using the alkaline elution technique it was shown that the effect of a large dose of light was to inhibit both initiation and elongation of DNA chains. These effects were most pronounced for Tsub(i)=O. It is concluded that DNA damage in an active replicon can inhibit initiation of new replicons and that damage localized behind the replication fork can retard elongation of nascent DNA chains. This effect on chain elongation decreases with increased distance of the damage from the replication fork.

Prevention of chinese green tea on 3,4-benzopyrene-induced lung cancer and its mechanism in animal model

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Qihua GU

2008-08-01

Full Text Available Background and objective Chinese green tea is one of the daily consumption beverages in the world and is considered a promising cancer chemopreventive agent. In the present study, we investigate the role of lung cancer prevention by green tea and its mechanism. Methods Three groups of female SD rats were kept with the same feed. Rats in group A were administrated with 1% green tea drinking, while in group B and group C with water only. Animals in group A and group B were given 3,4-benzopyrene-corn oil mixture pulmonary injection fortnightly for 4 times, while in group C corn oil only. Rats were sacrificed 1 year after the first injection under narcotism. Lung tumors and lung tissues were performed H＆E staining for cancer identification. Each case of lung cancer was examined for expression of p53 and Bcl-2 with in situ hybridization analysis and immunohistochemistry staining. Results No cancer was found in rats in group C. However, in group B, 15 out of 20 rats were found generating lung cancer, and in group A, 6 out of 20 rats inducing lung cancer were recorded. The rate of lung carcinogenesis in rats was decreased from 75% to 30% by 1% chinese green tea oral administration (χ2=8.12, P0.05. However, significantly lower level of Bcl-2 expression was found in lung cancer tissues of group A than that of group B (P<0.05. Conclusion The results indicate that chinese green tea inhibits lung carcinogenesis. Chinese green tea can slightly upregulate expression of p53, but significantly downregulate expression of Bcl-2 in lung cancer, and this may be related to the mechanism of lung cancer prevention.

Modification of the repair of potentially lethal damage in plateau-phase Chinese hamster cells by 2-chlorodeoxyadenosine

International Nuclear Information System (INIS)

Tanabe, Kiyoshi; Hiraoka, Wakako; Kuwabara, Mikinori; Matsuda, Akira; Ueda, Tohru; Sato, Fumiaki.

1988-01-01

The ability of 2-chlorodeoxyadenosine, a ribonucleotide reductase inhibitor, to inhibit the repair of potentially lethal damage was demonstrated in Chinese hamster V79 cells after X irradiation in plateau-phase cultures. This ability of the drug was completely diminished when deoxycytidine was added at the same time, though this was slightly affected by the addition of adenosine, suggesting that this drug was phosphorylated by deoxycytidine kinase to serve as an inhibitor of the repair of potentially lethal damage. Compared with hydroxyurea, another ribonucleotide reductase inhibitor, this drug appeared to contain its own activity which suppressed the repair of potentially lethal damage. A combined study of post-irradiation treatment with hypertonic salt solution and with this drug on the fixation of potentially lethal damage revealed that this drug inhibited the repair of hypertonic-insensitive potentially lethal damage. (author)

Modification of the repair of potentially lethal damage in plateau-phase Chinese hamster cells by 2-chlorodeoxyadenosine

Energy Technology Data Exchange (ETDEWEB)

Tanabe, Kiyoshi; Hiraoka, Wakako; Kuwabara, Mikinori; Matsuda, Akira; Ueda, Tohru; Sato, Fumiaki.

1988-09-01

The ability of 2-chlorodeoxyadenosine, a ribonucleotide reductase inhibitor, to inhibit the repair of potentially lethal damage was demonstrated in Chinese hamster V79 cells after X irradiation in plateau-phase cultures. This ability of the drug was completely diminished when deoxycytidine was added at the same time, though this was slightly affected by the addition of adenosine, suggesting that this drug was phosphorylated by deoxycytidine kinase to serve as an inhibitor of the repair of potentially lethal damage. Compared with hydroxyurea, another ribonucleotide reductase inhibitor, this drug appeared to contain its own activity which suppressed the repair of potentially lethal damage. A combined study of post-irradiation treatment with hypertonic salt solution and with this drug on the fixation of potentially lethal damage revealed that this drug inhibited the repair of hypertonic-insensitive potentially lethal damage.

Tumor production in Syrian hamsters following inhalation of PuO2--ZrO2 aerosol

International Nuclear Information System (INIS)

Thomas, R.G.; Smith, D.M.

1978-01-01

Syrian golden hamsters of both sexes were exposed to aerosols of ZrO 2 containing PuO 2 . The starting material in the aerosol generator also had a small amount of 57 Co added as a tracer. The mixture of all three constituents was nebulized and the droplets passed through a heating column at 1000 0 C. Aerosol sampling was accomplished with a cascade impactor and electrostatic precipitator. The median aerodynamic diameters in all inhalation runs were approximately 2 μm with a geometric standard deviation of 2. One exposed group of 60 hamsters had 6-day lung burdens averaging 100 nCi. This group had a lung tumor incidence of 44% with an even distribution of adenomas and carcinomas. Two other groups had average 6-day lung burdens of 80 to 90 nCi plus 55 nCi of intravenously injected spheres localized in the lung. These animals had tumor incidences of approximately 30%

Effects of D,L-buthionine-S,R-sulfoximine on cellular thiol levels and the oxygen effect in Chinese hamster V79 cells

International Nuclear Information System (INIS)

Astor, M.B.; Hall, E.J.; Biaglow, J.E.; Hartog, B.

1984-01-01

The role of glutathione (GSH) and total non-protein thiols (NPSH) in repairing radiation-induced free radical damage incurred under aerated and hypoxic conditions was investigated using Chinese hamster V79 cells cultured in vitro. GSH and NPSH levels were depleted in V79 cells of varying cell densities using the gamma-glutamyl-cysteine-synthetase inhibitor, D,L-Buthionine-S,R-sulfoximine (BSO). A small change in hypoxic cell radiosensitivity could be attributed to the loss of GSH while depletion of thiols to lower levels affected both aerated and hypoxic cell radiosensitivity, resulting in no change in the OER

UGT1A6 polymorphisms modulated lung cancer risk in a Chinese population.

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Ley-Fang Kua

Full Text Available Uridine diphosphoglucuronosyltransferases (UGTs 1A6 is the only UGT1A isoform expressed in lung tissue. It is responsible for the detoxification of carcinogens such as benezo[a]pyrene from cigarette smoke. The purpose of this study was to evaluate the association of UGT1A6 polymorphisms and haplotypes with lung cancer risk and to evaluate the functional significance of UGT1A6 polymorphisms. Genomic DNA was isolated from leukocytes. Eight UGT1A6 polymorphisms were sequenced in a test set of 72 Chinese lung cancer patients and 62 healthy controls. Potential risk modifying alleles were validated in a separate set of 95 Chinese lung cancer patients and 100 healthy controls. UGT1A6 19T>G, 541A>G and 552A>C showed significant association with increased lung cancer risk, while UGT1A6 105C>T and IVS1+130G>T were significantly associated with reduced lung cancer risk. Multivariate logistic regression analysis demonstrated a significant association of lung cancer with UGT1A6 541A>G (OR: 3.582, 95% CI: 1.27-10.04, p = 0.015, 552A>C (OR: 5.364, 95% CI: 1.92-14.96, p = 0.001 and IVS1+130G>T (OR: 0.191, 95% CI: 0.09-0.36, pT increased mRNA stability, providing a plausible explanation of its association with reduced lung cancer risk. Thus UGT1A6 polymorphisms may be used to identify people with increased risk of developing lung cancer.

Genetic effects of the flavonols quercetin, kaempferol, and galangin on Chinese hamster ovary cells in vitro

Energy Technology Data Exchange (ETDEWEB)

Carver, J.H. (Lawrence Livermore National Lab., Livermore, CA); Carrano, A.V.; MacGregor, J.T.

1983-01-01

The genotoxicity of selected flavonols was evaluated by multiple endpoints in Chinese hamster ovary (CHO) cells. Chromosomal aberrations, sister-chromatid exchange (SCE), and forward mutation at 4 gene loci were measured in a single population of cells exposed to quercetin, kaempferol, or galangin for 15 h with and without metabolic activation. The incidence of chromosomal aberrations was significantly increased by quercetin in the absence of activation and by kaempferol and galangin with and without activation. Flavanol treatment affected SCE and mutation at the hgprt, aprt, or Na/sup +//K/sup +/-ATPase loci only marginally, but significantly increased mutation frequencies at the tk locus. The response at the tk locus suggests that the CHO cells may behave similarly to L5178Y cells, in which the tk locus is thought to reflect chromosomal lesions in addition to point mutation. These results indicate that, at least under the conditions examined, flavonols induce chromosomal aberrations in CHO cells, but have little effect on point mutation or SCE.

Perturbation of N-linked oligosaccharide structure results in an altered incorporation of [3H]palmitate into specific proteins in Chinese hamster ovary cells

International Nuclear Information System (INIS)

Wellner, R.B.; Ghosh, P.C.; Roecklein, B.; Wu, H.C.

1987-01-01

Increased [ 3 H]palmitate incorporation into specific cellular proteins has been reported to occur in Chinese hamster ovary and yeast mutant cells. In this paper we report studies concerning the relationship between N-linked oligosaccharide structure and [ 3 H]palmitate incorporation into proteins of Chinese hamster ovary (CHO) cells. We have compared the incorporation of [ 3 H]palmitate into proteins of wild-type and four different mutant CHO cell lines defective in various steps of N-linked protein glycosylation. Sodium dodecyl sulfate-gel electrophoretic analysis showed that three of the mutants exhibited increased [ 3 H]palmitate incorporation into several CHO cellular proteins (approximately 30,000-38,000 molecular weight) as compared to the wild-type cells. One of the affected mutants which accumulates the Man5Gn2Asn intermediate structure was examined in detail. In agreement with earlier reports, virtually all of the [ 3 H] palmitate-labeled proteins of both wild-type and mutant cell lines are membrane-bound. Pretreatment of the mutant cell line with tunicamycin blocked the increased [ 3 H]palmitate incorporation into the two specific proteins (both of approximately 30,000 molecular weight) observed in untreated cells; the decreased incorporation of [ 3 H]palmitate into the 30,000 molecular weight species was accompanied by a concomitant increase in the incorporation of [ 3 H]palmitate into two proteins of approximately 20,000 molecular weight. Pretreatment of wild-type cells with tunicamycin also caused increased [ 3 H]palmitate incorporation into the 20,000 molecular weight species

Dotriacontane-16,17-14C distribution pattern in the respiratory system of two hamster species after passive exposure to radioactive labelled smoke

International Nuclear Information System (INIS)

Kmoch, N.; Mohr, U.

1974-01-01

The quantitative and qualitative distribution of 14 C labeled dotriacontane (DOT- 14 C) determined by liquid scintillation counting and autoradiography in the respiratory system, the digestive tract, liver and kidneys of Syrian golden and European hamsters, males and females, is described after they had been exposed to radioactive labeled cigarette smoke. The different DOT- 14 C distributions are discussed in detail with special attention given to the respiratory tract, related species differences and the topographic subdivisions of apex nasi, fundus nasi, pharynx, larynx, trachea, and lungs. It is apparent that the absolute amount of activity in the respiratory tract related to body size of the Syrian golden hamster is greater than in the European hamster but that the percentual distribution exhibits a greater filtering action of the upper respiratory tract of Syrian golden hamster than of the European hamster so that a larger percentual amount of total inhaled particulate matter reaches the lungs. The European hamster might be a more useful model for the investigation of respiratory tract carcinogenesis due to the possibility of a longer life time exposure and a higher sensitivity to respiratory tract carcinogens

Effect of anolyte on growth and division of Chinese hamster cancerous cells

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saeed Mohammadzadeh

2009-04-01

Full Text Available Background: At present, cancer can be controlled by chemotherapy, but unfortunately, this method has strong side effects and scientist try to reduce them using different substances. 2 kinds of activated water called anolyte and catholyte have electrochemical property and antibacterial and oxidative properties respectively. The aim of this research is to study the effect of anolyte on growth and division of cancerous cells. Materials and Methods: In this research, different concentration of anolyte, 1 . 7, 2, 5,8.3 and 10 percent of anolyte and control with 2 and 5 percent of serum physiologic were added on converted cell of Chinese hamster (line b11dii-FAF28 clone 237 in 12 plastic and 15 glass flasks. After adding, converted cell was counted with the help of hoemocytometer and microscope. Data of experiment analyzed and results compared by t test, as well as using Excell software their diagrams were drawn. Results: The results indicated that anolyte had significant effect on cancer cells. In concentration of 1.7% cell division was decreased but in concentration of 8.3 %, division of cancerous cells was blocked and cells were fixed. Conclusion: Considering the low amount of sodium chloride in anolyte, it seems that, this solution (Anolyte hasn’t side effects and advers effect on the cells body.

Effects of inhibitors of protein kinase C and NO-synthase on the radiation-induced cytogenetic adaptive response in Chinese hamster cells in culture

International Nuclear Information System (INIS)

Gil'yano, N.Ya.; Bondarev, G.N.; Bikineeva, E.G.; Krasotskaya, G.I.; Noskin, L.A.

2001-01-01

The effect of the serine-threonin kinase inhibitor - staurosporine and inhibitor of NO-synthase - L-NAME on the radiation-induced adaptive response were studied in fibroblasts of Chinese hamster in culture. It is shown that staurosporine and L-NAME inhibit cytogenetic adaptive response induced by β-particles in low doses. Inhibition is not connected with radiosensitizing effect of these agents. L-NAME decreases significantly the γ-rays-induced chromosome aberration yield also. Study confirms the role of protein kinase C in induction of the adaptive response and participation of NO-synthase in this process is noticed for the first time [ru

Ascorbate enhances u.v.-mutagenesis in E. coli but inhibits it in Chinese hamster cells

International Nuclear Information System (INIS)

Rossman, T.G.; Klein, C.B.; Naslund, M.

1986-01-01

Ascorbic acid (vitamin C) causes an increase in the mutation frequency of u.v.-irradiated Escherichia coli WP2. The enhancement occurs at all u.v. fluences, and is dependent upon the ascorbate concentration in the medium. A maximum effect (approx. 8- to 13-fold) is seen at 100-150 μg/ml, although some enhancement can be seen even at 10 μg/ml. The comutagenic effect of ascorbate with u.v. in E. coli is dependent upon peptone, a constituent of nutrient broth. The enhancement of u.v.-mutagenesis by ascorbate is absent in strains WP2sub(s) (uvrA) amd WP6 (polA), suggesting that ascorbate affects the repair of pyrimidine dimers. The opposite results are observed for u.v.-mutagenesis in Chinese hamster V79 cells. The presence of ascorbate (50 μg/ml) during u.v. irradiation does not enhance the u.v. effect, but rather decreases it approx. 30%. These results are discussed with regard to differences in the mechanism of u.v.-mutagenesis and DNA repair in bacterial and mammalian cells. (author)

Diethyldithiocarbamate concentration effects and interactions with other cytotoxic agents on Chinese hamster cells (V79)

International Nuclear Information System (INIS)

Lin, P.S.; Quamo, S.; Ho, K.C.; Baur, K.

1985-01-01

A metal chelator, diethyldithiocarbamate (DDC) perturbs the chromosome condensation processes in dividing cells. The length of the metaphase chromosomes in Chinese hamster cells (V79) treated with 17.2 μg/ml of DDC for 2 hr is about half of that in untreated cells. However, concentrations of 1.7 μg or 172 μg/ml DDC apparently do not produce this effect. DDC at 17.2 μg/ml also disrupts spindle fibers. Bleomycin, but not mitomycin and cisplatin, added simultaneously with DDC can prevent the DDC effect on chromosomes. The cytotoxic effect of increasing concentrations of DDC can prevent the DDC effect on chromosomes. The cytotoxic effect of increasing concentrations of DDC to V79 cells incubated at 37 0 C exhibits a similar biphasic response. This concentration biphasic toxic effect is not altered when the cells are treated with DDC in combination with radiation, heat, or other cytotoxic drugs. These observations suggest that the different effects of DDC concentrations on chromosome condensation should be considered as one important modification factor for DDC related toxicity

Histologic observations on the pathogenesis of lung cancer in hamsters following administration of polonium-210

International Nuclear Information System (INIS)

Lisco, H.; Kennedy, A.R.; Little, J.B.

1974-01-01

A serial sacrifice experiment was carried out to study the site of origin and the stages in development of lung cancer in hamsters induced by polonium-210 ( 210 Po). 1 or 2 animals were sacrificed weekly during and after a course of 7 intratracheal instillations of 0.1 μCi of 210 Po in saline. This exposure produced a transient radiation pneumonitis of moderate severity during, and for several weeks after, the instillation period. Subsequent pathological changes included hyperplasia of bronchiolar epithelium, and focal proliferation of epithelial cells in peribronchiolar and more remote alveoli, termed epithelialization of alveoli. Hyperplastic bronchiolar epithelium frequently showed numerous Clara cells which exhibited pleomorphism of cells and nuclei, multinucleated cells, and striking changes in staining characteristics of secretory granules. Epithelialization of alveoli showed steady progression from well-circumscribed small foci to larger confluent lesions which were composed of various cell types and resembled tumors. Malignant tumors occurred in many animals surviving more than 24 weeks after the last instillation of 210 Po

A uv-sensitive Chinese hamster lung fibroblast cell line (V79/UC) with a possible defect in DNA polymerase activity is deficient in DNA repair

International Nuclear Information System (INIS)

Creissen, D.M.; Hill, C.K.

1991-01-01

Studies of repair enzyme activities in a uv-sensitive cell line (V79/UC) derived from Chinese hamster V79 cells have revealed levels of total DNA polymerase that are about 50% of the levels in the parental cell line. There are a number of DNA polymerase inhibitors available which allow us to distinguish between the major forms of DNA polymerase (alpha, beta, gamma, and delta) identified in mammalian cells. Enzyme assays with these inhibitors indicate that the aphidicolin-sensitive DNA polymerase is defective in the V79/UC cell line. This could be either polymerase alpha or delta, or both. The V79/UC cells do not express resistance to aphidicolin in standard toxicity studies. However, when aphidicolin is added postirradiation in survival assays designed to measure the extent of inhibitable repair, V79/UC cells do not respond with the further decrease in survival seen in the parental line. Further evidence of a polymerase-dependent repair defect is evident from alkaline elution data. In this case the V79/UC cells show the appearance of single-strand breaks following uv irradiation in the absence of any added inhibitor. Cells of the V79/M12G parental line, on the other hand, show the appearance of single-strand breaks only when aphidicolin is present

Centriole distribution during tripolar mitosis in Chinese hamster ovary cells

Science.gov (United States)

1984-01-01

During bipolar mitosis a pair of centrioles is distributed to each cell but the activities of the two centrioles within the pair are not equivalent. The parent is normally surrounded by a cloud of pericentriolar material that serves as a microtubule-organizing center. The daughter does not become associated with pericentriolar material until it becomes a parent in the next cell cycle (Rieder, C.L., and G. G. Borisy , 1982, Biol. Cell., 44:117-132). We asked whether the microtubule-organizing activity associated with a centriole was dependent on its becoming a parent. We induced multipolar mitosis in Chinese hamster ovary cells by treatment with 0.04 micrograms/ml colcemid for 4 h. After recovery from this colcemid block, the majority of cells divided into two, but 40% divided into three and 2% divided into four. The tripolar mitotic cells were examined by antitubulin immunofluorescence and by high voltage electron microscopy of serial thick (0.25-micron) sections. The electron microscope analysis showed that centriole number was conserved and that the centrioles were distributed among the three spindle poles, generally in a 2:1:1 or 2:2:0 pattern. The first pattern shows that centriole parenting is not prerequisite for association with pole function; the second pattern indicates that centrioles per se are not required at all. However, the frequency of midbody formation and successful division was higher when centrioles were present in the 2:1:1 pattern. We suggest that the centrioles may help the proper distribution and organization of the pericentriolar cloud, which is needed for the formation of a functional spindle pole. PMID:6373793

Diethyldithiocarbamate enhancement of radiation and hyperthermic effects on Chinese hamster cells in vitro

International Nuclear Information System (INIS)

Lin, P.S.; Kwock, L.; Butterfield, C.E.

1979-01-01

To test the possibility of enhancing O 2 - toxicity during radiation therapy and/or hyperthermia, Chinese hamster cells (Don) were treated with the drug diethyldithiocarbamate (DDC) in vitro. This drug has been shown to inhibit, both in vitro and in vivo, the enzyme superoxide dismutase (SOD) which is responsible for eliminating the 0 2 - radical in cells. We observed that the cytocidal effect of DDC on Don cells is dependent on both DDC concentration and exposure time. After 8 to 10 days of incubation with 10 -9 M DDC, no change in cell survival was noted; however, incubation with 10 -4 M DDC produced a marked loss in colony formation. When DDC-treated cells were γ-irradiated, they did not survive as well as cells that were treated with either radiation or DDC alone. The combined effects of hyperthermia and DDC were dramatic. Cells treated 5 min at 43 0 C with 10 -4 M DDC or 10 min at 43 0 C with 10 -5 M DDC showed significant decrease in survival. These results suggest that DDC may be a potentially powerful sensitizing agent in tumor therapy, since there is increasing evidence that tumor cells have a lower level of superoxide dismutase

Cultured Chinese hamster cells undergo apoptosis after exposure to cold but nonfreezing temperatures.

Science.gov (United States)

Nagle, W A; Soloff, B L; Moss, A J; Henle, K J

1990-08-01

Cultured Chinese hamster V79 fibroblast cells at the transition from logarithmic to stationary growth have been shown to undergo apoptosis (programmed cell death) after cold shock [B. L. Soloff, W. A. Nagle, A. J. Moss, Jr., K. J. Henle, and J. T. Crawford, Biochem. Biophys. Res. Commun. 145, 876-883 (1987)]. In this report, we show that about 95% of the cell population was susceptible to cold-induced apoptosis, and the amount of cell killing was dependent on the duration of hypothermia. Cells treated for 0-90 min at 0 degrees C exhibited an exponential survival curve with a D0 of 32 min; thus, even short exposures to the cold (e.g., 5 min) produced measurable cell killing. The cold-induced injury was not produced by freezing, because similar results were observed at 6 degrees C, and cell killing was not influenced by the cryoprotective agent dimethyl sulfoxide. Cold-induced apoptosis was inhibited by rewarming at 23 degrees C, compared to 37 degrees C, by inhibitors of macromolecular synthesis, such as cycloheximide, and by 0.8 mM zinc sulfate. The results suggest that apoptosis represents a new manifestation of cell injury after brief exposure to 0-6 degrees C hypothermia.

The mutation studies of mutagen-sensitive and DNA repair mutants of Chinese hamster fibroblasts

International Nuclear Information System (INIS)

Schultz, R.A.; Chang, C.C.; Trosko, J.E.

1981-01-01

We have previously reported the isolation and partial characterization of DNA repair and/or mutagen-sensitive mutant Chinese hamster cell strains. Here we present the results of a detailed study of the ultraviolet light (UV)-induced mutability of one of these strains, UVs-7, and provide preliminary mutability data on two additional lines, UVr-23 and UVs-40. UVs-7 in extremely deficient in unscheduled DNA synthesis (UDS) but only slightly more sensitive to UV than the parental line. When examined for the UV-inducibility of mutants resistant to ouabain, 6-thioguanine, or diphtheria toxin, UVs-7 was found to be hypermutable at all three loci as compared to the parental line. The degree of hypermutability was not the same for any two loci. UVs-40, a highly UV-sensitive strain, was also found to be hypermutable at the ouabain-resistant (ouar) locus. UVr-23, which is UV-resistant and more proficient at UDS than the parental line, appeared to exhibit a tendency toward hypomutability at both the ouabain(ouar) and 6-thioguanine--resistant (6TGr) loci. Further characterization of all these lines should aid in delineating mammalian mechanisms of DNA repair and mutagenesis

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

International Nuclear Information System (INIS)

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

1990-01-01

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

Raw Garlic Consumption and Lung Cancer in a Chinese Population.

Science.gov (United States)

Myneni, Ajay A; Chang, Shen-Chih; Niu, Rungui; Liu, Li; Swanson, Mya K; Li, Jiawei; Su, Jia; Giovino, Gary A; Yu, Shunzhang; Zhang, Zuo-Feng; Mu, Lina

2016-04-01

Evidence of anticancer properties of garlic for different cancer sites has been reported previously in in vitro and in vivo experimental studies but there is limited epidemiologic evidence on the association between garlic and lung cancer. We examined the association between raw garlic consumption and lung cancer in a case-control study conducted between 2005 and 2007 in Taiyuan, China. Epidemiologic data was collected by face-to-face interviews from 399 incident lung cancer cases and 466 healthy controls. We used unconditional logistic regression models to estimate crude and adjusted ORs (aOR) and their 95% confidence intervals (CI). Adjusted models controlled for age, sex, average annual household income 10 years ago, smoking, and indoor air pollution. Compared with no intake, raw garlic intake was associated with lower risk of development of lung cancer with a dose-response pattern (aOR for garlic consumption with indoor air pollution and with any supplement use in association with lung cancer. The results of the current study suggest that raw garlic consumption is associated with reduced risk of lung cancer in a Chinese population. This study contributes to the limited research in human population on the association between garlic and lung cancer and advocates further investigation into the use of garlic in chemoprevention of lung cancer. Cancer Epidemiol Biomarkers Prev; 25(4); 624-33. ©2016 AACR. ©2016 American Association for Cancer Research.

Inhibition of apoptosis using exosomes in Chinese hamster ovary cell culture.

Science.gov (United States)

Han, Seora; Rhee, Won Jong

2018-05-01

Animal cell culture technology for therapeutic protein production has shown significant improvement over the last few decades. Chinese hamster ovary (CHO) cells have been widely adapted for the production of biopharmaceutical drugs. In the biopharmaceutical industry, it is crucial to develop cell culture media and culturing conditions to achieve the highest productivity and quality. However, CHO cells are significantly affected by apoptosis in the bioreactors, resulting in a substantial decrease in product quantity and quality. Thus, to overcome the obstacle of apoptosis in CHO cell culture, it is critical to develop a novel method that does not have minimal concern of safety or cost. Herein, we showed for the first time that exosomes, which are nano-sized extracellular vesicles, derived from CHO cells inhibited apoptosis in CHO cell culture when supplemented to the culture medium. Flow cytometric and microscopic analyses revealed that substantial amounts of exosomes were delivered to CHO cells. Higher cell viability after staurosporine treatment was observed by exosome supplementation (67.3%) as compared to control (41.1%). Furthermore, exosomes prevented the mitochondrial membrane potential loss and caspase-3 activation, meaning that the exosomes enhanced cellular activities under pro-apoptotic condition. As the exosomes supplements are derived from CHO cells themselves, it is not only beneficial for the biopharmaceutical productivity of CHO cell culture to inhibit apoptosis, but also from a regulatory standpoint to diminish any safety concerns. Thus, we conclude that the method developed in this research may contribute to the biopharmaceutical industry where minimizing apoptosis in CHO cell culture is beneficial. © 2018 Wiley Periodicals, Inc.

The suppressive effect of etoposide on recovery from sublethal radiation damage in Chinese hamster V 79 cells

International Nuclear Information System (INIS)

Saito, Tsutomu; Shimada, Yuji; Kawamori, Jiro; Kamata, Rikisaburo

1992-01-01

The combined effect of radiation and etoposide on the survival of cultured Chinese hamster V 79 cells was investigated. Cells in exponential growth phase were treated with various combinations of radiation and etoposide. The surviving fraction was assessed by colony formation. Etoposide significantly reduced so-called shoulder width, as expressed in Dq (quasithreshold dose), of radiation survival curves. The reduction depended on the increase of etoposide concentrations, although steepening of slopes of exponentially regressing portions of the radiation survival curves was slight. Split dose experiments showed that cells did not recover from sublethal radiation damage in the presence of low concentration of etoposide, although they did recover from sublethal radiation damage under a drug free condition. The results show the suppressive effect of etoposide on recovery from sublethal radiation damage. The effect of a sequential combination of radiation and etoposide was also investigated. The effect was more marked when the interval between radiation and etoposide was shorter regardless of the sequence. (author)

Effects of diazepam on Mycobacterium bovis-induced infection in hamsters

Directory of Open Access Journals (Sweden)

Righi D.A.

1999-01-01

Full Text Available The in utero exposure of hamsters to low doses of diazepam results in impaired host defense against Mycobacterium bovis during adulthood. Delayed developmental immunotoxicity, however, represents a specific situation that might not be general. The present experiment was undertaken to investigate the effects of diazepam on hamster resistance to M. bovis using adult animals. The effects of diazepam treatment on serum cortisol levels were also studied. Adult hamsters (N = 10 for each group were treated with diazepam (E1 = 1.0, E2 = 2.0 or E3 = 3.0 mg kg-1 day-1 subcutaneously or with control solution (C for 30 days. Seven days after the beginning of the treatment, the animals received identical inoculum concentrations of M. bovis. Hamsters treated with the higher (2.0 and 3.0 mg kg-1 day-1 doses of diazepam exhibited: 1 increased granuloma areas in the liver (C = 1.81 ± 1.39, E2 = 10.29 ± 4.64 and E3 = 15.80 ± 4.82 and lung (C = 0.54 ± 0.55, E2 = 6.28 ± 3.85 and E3 = 6.31 ± 3.56 and 2 increased scores of M. bovis colony-forming units isolated from liver (C = 2.0, E2 = 3.0 and E3 = 3.5, lung (C = 1.0, E2 = 3.0 and E3 = 3.5 and spleen (C = 1.0, E2 = 2.5 and E3 = 4.0. These effects were dose dependent, and were not detected or were less severe in animals treated with the lowest (1.0 mg/kg dose of diazepam as well as in those of the control group. Furthermore, diazepam treatment (3.0 mg kg-1 day-1 for 30 days increased (E3 = 71.32 ± 2.99; N = 10 the serum levels of cortisol compared to control hamsters (C = 22.61 ± 2.75; N = 10. The present data, that demonstrate an impaired defense against M. bovis in adult hamsters treated with diazepam, were tentatively explained on the basis of a direct and/or indirect action of diazepam on the cytokine network. The effects may be related to stimulation of peripheral benzodiazepine receptor binding sites (PBR by macrophages and/or lymphocytes, or they may be mediated by PBR stimulation of the adrenals.

Gamma-ray induced DNA breaks and repair studied by immuno-labelling of poly(ADP-ribose) polymerase (PARP) in chinese hamster ovary cells (CHO)

International Nuclear Information System (INIS)

Bidon, N.; Noel, G.; Averbeck, D.; Varlet, P.; Salamero, J.; DeMurcia, G.

1998-01-01

The poly(ADP-ribose)polymerase is a nuclear ubiquitous enzyme capable of binding to DNA breaks. Chinese hamster ovary cells were (CHO-K1) cultured on slides and γ-irradiated ( 137 Cs) at a high (12.8 Gy/min) or medium dose rate (5 Gy/min), and immuno-labelling against (ADP-ribose) polymers immediately or three hours after irradiation. Quantification and localisation of γ-ray induced breaks was performed by confocal microscopy. The results show a dose effect relationship, a dose-rate effect and the signal disappearance after 3 hours at 37 deg.C. The presence of PARP activity appears to reflect γ-rays induced DNA fragmentation. (authors)

Sodium butyrate affects the cytotoxic and mutagenic response of V79 Chinese hamster cells to the genotoxic agents, daunorubicin and U.V. radiation

International Nuclear Information System (INIS)

Pani, B.; Babudri, N.; Giancotti, V.; Russo, E.

1984-01-01

It has been suggested that conditions which lead to modifications in the chromatin structure could be responsible for an increased accessibility of DNA to genotoxic agents in eukaryotic cells. With this in mind, the cytotoxic and mutagenic activity of the anthracycline antibiotic, daunorubicin, and of UV radiation was assayed on V79 Chinese hamster cells pretreated or not with 5 mM sodium butyrate, an agent known to induce modifications in the chromatin structure: this treatment in fact proved to induce the hyperacetylation of the core histones, and moreover to enhance the cytotoxic response of the cells to both daunorubicin and UV radiation and the mutagenic response to daunorubicin. (orig.)

Enhancement of excision-repair efficiency by conditioned medium from density-inhibited cultures in V79 Chinese hamster cells

International Nuclear Information System (INIS)

Nakano, S.

1979-01-01

Conditioned medium from density-inhibited V79 Chinese hamster cell cultures, given as a post-treatment to UV-irradiated homologous cells, was demonstrated to reduce the lethal action of ultraviolet light by temporarily blocking DNA replication. Since the increased survival was not affected by various nontoxic concentrations of caffeine, such protective effect would be attributable to the prolonged intervention of excision repair before DNA replication during the post-treatment period. The influence of conditioned medium on the UV-induced mutation at the ouabain-resistance locus was also examined and a significant decrease in mutation frequecy was noted. The observed reduction in killing and mutation as a result of post-incubation in conditioned medium, which delays DNA replication, would be interpreted as evidence that conditioned medium provides a longer period of time for an error-free excision-repair process, leaving lesion in DNA available for error-prone post-replication repair. (Auth.)

Modification of thermal sensitivity of Chinese hamster cells by exposure to solutions of monovalent and divalent cationic salts

International Nuclear Information System (INIS)

Raaphorst, G.P.; Azzam, E.I.; Vadasz, J.

1984-06-01

Chinese hamster V79 cells were heated in culture medium or in 0.155-mol.dm -3 solutions of LiCl, NaCl, KCl, MgCl 2 , CaCl 2 and BaCl 2 . The presence of any one of these ionic solutions during heating increased the thermal sensitivity of the cells. The order of increased thermal sensitivity was KCl > LiCl > NaCl for the monovalent salts and BaCl 2 > MgCl 2 > CaCl 2 for the divalent cation salts. The addition of glucose to LiCl or NaCl solutions did not reduce the thermal sensitization caused by these solutions. When cells were sensitized by LiCl or NaCl treatment, a change in pH from 7.2 to 6.6 did not further increase thermal sensitivity. These data show that nutrient and ionic factors and their interplay are involved in cellular thermal sensitivity

Regional assignment of seven genes on chromosome 1 of man by use of man-Chinese hamster somatic cell hybrids. II. Results obtained after induction of breaks in chromosome 1 by X-irradiation.

Science.gov (United States)

Burgerhout, W G; Smit, S L; Jongsma, A P

1977-01-01

The position of genes coding for PGD, PPH1, UGPP, GuK1, PGM1, Pep-C, and FH on human chromosome 1 was investigated by analysis of karyotype and enzyme phenotypes in man-Chinese hamster somatic cell hybrids carrying aberrations involving chromosome 1. Suitable hybrid cell lines were obtained by X-irradiation of hybrid cells carrying an intact chromosome 1 and by fusion of human cells from a clonal population carrying a translocation involving chromosome 1 with Chinese hamster cells. The latter human cell population had been isolated following X-irradiation of primary Lesch-Nyhan fibroblasts. In addition, products of de novo chromosome breakage in the investigated hybrid lines were utilized. By integrating the results of these analyses with earlier findings in our laboratory, the following positions of genes are deduced: PGD and PPH1 in 1p36 leads to 1p34; PGM1 in 1p32; UGPP in 1q21 leads to 1q23; GuK1 in 1q31 leads to 1q42; Pep-C in 1q42; and FH in 1qter leads to 1q42.

Association between cooking oil fume exposure and lung cancer among Chinese nonsmoking women: a meta-analysis.

Science.gov (United States)

Xue, Yingbo; Jiang, Ying; Jin, Shan; Li, Yong

2016-01-01

Lung cancer has been the main cause of cancer death around the world. Cigarette smoking has been identified as a risk factor for lung cancer in males. However, the etiological factors in nonsmoking women remain elusive. A meta-analysis was conducted to evaluate the relationship between cooking oil fume exposure and lung cancer among Chinese nonsmoking women. Thirteen articles containing three population-based case-control and ten hospital-based case-control studies were included in this meta-analysis. These studies with a total of 3,596 lung cancer women and 6,082 healthy controls were analyzed by RevMan 5.3. Fixed effects model or random effects model was used to obtain pooled estimates of risk ratio. The risk ratios with a 95% CI were 1.74 (95% CI =1.57-1.94) and 2.11 (95% CI =1.54-2.89), respectively. Cooking oil fume exposure as well as not using a kitchen ventilator when cooking was significantly associated with lung cancer among nonsmoking women (Z=10.07, Poil fume exposure, especially lacking a fume extractor, may increase the risk of lung cancer among Chinese nonsmoking women.

Semi-conservative synthesis of DNA in UV-sensitive mutant cells of Chinese hamster after UV-irradiation

International Nuclear Information System (INIS)

Vikhanskaya, F.L.; Khrebtukova, I.A.; Manuilova, E.S.

1985-01-01

A study was made of the rate of semi-conservative DNA synthesis in asynchronous UV-resistant (clone V79) and UV-sensitive clones (VII and XII) of Chinese hamster cells after UV-irradiation. In all 3 clones studied, UV-irradiation (5-30 J/m 2 ) induced a decrease in the rate of DNA synthesis during the subsequent 1-2 h. In the resistant clone (V79) recovery of DNA synthesis rate started after the first 2 h post-irradiation (5 J/m 2 ) and by the 3rd hour reached its maximum value, which constituted 70% of that observed in control, non-irradiated cells. The UV-sensitive mutant clones VII and XII showed no recovery in the rate of DNA synthesis during 6-7 h post-irradiation. The results obtained show that the survival of cells is correlated with the ability of DNA synthesis to recover after UV-irradiation in 3 clones studied. The observed recovery of UV-inhibited DNA synthesis in mutant clones may be due to certain defects in DNA repair. (orig.)

Effects of 5 Thio-D-Glucose on cellular adenosine triphosphate levels and deoxyribonucleic acid rejoining in hypoxic and aerobic Chinese hamster cells

International Nuclear Information System (INIS)

Nagle, W.A.; Moss, A.J. Jr.; Roberts, H.G. Jr.; Baker, M.L.

1980-01-01

Intracellular adenosine triphosphate (ATP) levels were measured in both hypoxic and aerobic cultures of V79 Chinese hamster cells treated with 5-thio-D-glucose (5-SH-D-Glc). This glucose analog, a known inhibitor of D-glucose transport and metabolism, reduced ATP in cell cultures allowed to become hypoxic by cell metabolism, but not in aerobic cultures treated similarly. Cells depleted of ATP were unable to rejoin x-ray induced deoxyribonucleic acid (DNA) strand breaks as measured by the alkaline sucrose gradient sedimentation technique. The inference for radiation therapy is that inhibition of glucose metabolism selectively depletes energy reserves in hypoxic cells, rendering these cells more radiosensitive and leading to a more effective tumor treatment

Cell inactivation and chromosomal aberrations induced by X-rays and fast neutrons in cells of the Chinese hamster. 1

International Nuclear Information System (INIS)

Tolkendorf, E.

1979-01-01

Asynchronously grown cultures of Chinese hamster cells V79-4 were irradiated in suspension with 180 kV X-rays and fast neutrons (average energy of 6.2 MeV). The damage was assessed by measuring cell survival and frequencies of chromosome aberrations in the first post-irradiation metaphases. The experimental data for survival and chromosome aberrations were fitted by computer programmes. From the fitted curves the relative biological effectiveness (RBE) of fast neutrons was calculated. The RBE shows a similar dose dependence for killed and aberrant cells. The RBE decreases with increasing dose and amounts to approximately 5 for both effects for small neutron doses. The highest RBE is found for asymmetrical chromosomal exchanges and is dependent on the neutron dose, too. However, for isochromatid deletions the RBE is dose independent with a value of 3.6. (author)

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

DEFF Research Database (Denmark)

Hjortoe, G.M.; Weilguny, D.; Willumsen, Berthe Marie

2005-01-01

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...

Glutathione S-transferase P1, gene-gene interaction, and lung cancer susceptibility in the Chinese population: An updated meta-analysis and review

Directory of Open Access Journals (Sweden)

Xue-Ming Li

2015-01-01

Full Text Available Aim of Study: To assess the impact of glutathione S-transferase P1 (GSTP1 Ile105Val polymorphism on the risk of lung cancer in the Chinese population, an updated meta-analysis and review was performed. Materials and Methods: Relevant studies were identified from PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure, and Chinese Biology Medicine published through January 22, 2015. The odds ratios (ORs and 95% confidence intervals (CIs were calculated to estimate the strength of the associations. Results: A total of 13 case-control studies, including 2026 lung cancer cases and 2451 controls, were included in this meta-analysis. Overall, significantly increased lung cancer risk was associated with the variant genotypes of GSTP1 polymorphism in the Chinese population (GG vs. AA: OR = 1.36, 95% CI = 1.01-1.84. In subgroup analyses stratified by geographic area and source of controls, the significant results were found in population-based studies (GG vs. AA: OR = 1.62, 95% CI: 1.13-2.31; GG vs. AG: OR = 1.49, 95% CI: 1.03-2.16; GG vs. AA + AG: OR = 1.55, 95% CI: 1.12-2.26. A gene-gene interaction analysis showed that there was an interaction for individuals with combination of GSTM1 (or GSTT1 null genotype and GSTP1 (AG + GG mutant genotype for lung cancer risk in Chinese. Conclusion: This meta-analysis suggests that GSTP1 Ile105Val polymorphism may increase the risk of lung cancer in the Chinese population.

CHRNA5 polymorphism and susceptibility to lung cancer in a Chinese population

Energy Technology Data Exchange (ETDEWEB)

Shen, Bo [Jiangsu Cancer Hospital, Department of Medical Oncology, Nanjing, Jiangsu Province (China); Zhu, Qun [Second Affiliated Hospital, Nanjing Medical University, Department of Endocrinology, Nanjing, Jiangsu Province (China); Zheng, Ma-Qing [College of Pharmacy, Nanjing University of Technology, Nanjing, Jiangsu Province (China); Chen, Jia; Shi, Mei-Qi; Feng, Ji-Feng [Jiangsu Cancer Hospital, Department of Medical Oncology, Nanjing, Jiangsu Province (China)

2013-01-11

Polymorphisms in the nicotinic acetylcholine receptor subunit CHRNA5 gene have been associated with lung cancer positive susceptibility in European and American populations. In the present hospital-based, case-control study, we determined whether polymorphism in rs503464 of CHRNA5 is associated with lung cancer risk in Chinese individuals. A single nucleotide polymorphism in CHRNA5 rs503464, c.-166T>A (hereafter T>A), was identified using TaqMan-MGB probes with sequencing via PCR in 600 lung cancer cases and 600 healthy individuals. Genotype frequencies for rs503464 (T>A) were in Hardy-Weinberg equilibrium for the control population. However, genotype frequencies were significantly different between cases and controls (P < 0.05), while allele frequencies were not significantly different between groups. Compared to homozygous genotypes (TT or AA), the risk of lung cancer in those with the heterozygous genotype (TA) was significantly lower (OR = 0.611, 95%CI = 0.486-0.768, P = 0.001). Using genotype AA as a reference, the risk of lung cancer for those with genotype TA was increased 1.5 times (OR = 1.496, 95%CI = 1.120-1.997, P = 0.006). However, no difference in risk was observed between T allele carriers and A allele carriers (OR = 0.914, 95%CI = 0.779-1.073, P = 0.270). Stratification analysis showed that the protective effect of TA was more pronounced in those younger than 60 years, nonsmokers, or those without a family history of cancer, as well as in patients with adenocarcinoma or squamous cell carcinoma in clinical stages III or IV (P < 0.05). Therefore, the heterozygous genotype c.-166T>A at rs503464 of CHRNA5 may be associated with reduced risk of lung cancer, thus representing a susceptibility allele in Chinese individuals.

CHRNA5 polymorphism and susceptibility to lung cancer in a Chinese population

International Nuclear Information System (INIS)

Shen, Bo; Zhu, Qun; Zheng, Ma-Qing; Chen, Jia; Shi, Mei-Qi; Feng, Ji-Feng

2013-01-01

Polymorphisms in the nicotinic acetylcholine receptor subunit CHRNA5 gene have been associated with lung cancer positive susceptibility in European and American populations. In the present hospital-based, case-control study, we determined whether polymorphism in rs503464 of CHRNA5 is associated with lung cancer risk in Chinese individuals. A single nucleotide polymorphism in CHRNA5 rs503464, c.-166T>A (hereafter T>A), was identified using TaqMan-MGB probes with sequencing via PCR in 600 lung cancer cases and 600 healthy individuals. Genotype frequencies for rs503464 (T>A) were in Hardy-Weinberg equilibrium for the control population. However, genotype frequencies were significantly different between cases and controls (P < 0.05), while allele frequencies were not significantly different between groups. Compared to homozygous genotypes (TT or AA), the risk of lung cancer in those with the heterozygous genotype (TA) was significantly lower (OR = 0.611, 95%CI = 0.486-0.768, P = 0.001). Using genotype AA as a reference, the risk of lung cancer for those with genotype TA was increased 1.5 times (OR = 1.496, 95%CI = 1.120-1.997, P = 0.006). However, no difference in risk was observed between T allele carriers and A allele carriers (OR = 0.914, 95%CI = 0.779-1.073, P = 0.270). Stratification analysis showed that the protective effect of TA was more pronounced in those younger than 60 years, nonsmokers, or those without a family history of cancer, as well as in patients with adenocarcinoma or squamous cell carcinoma in clinical stages III or IV (P < 0.05). Therefore, the heterozygous genotype c.-166T>A at rs503464 of CHRNA5 may be associated with reduced risk of lung cancer, thus representing a susceptibility allele in Chinese individuals

Investigation of the effect of radiation of DNA methylation patterns

International Nuclear Information System (INIS)

Kalinich, J.F.

1986-01-01

Four lines of cultured mammalian cells were used in this project: V79A03, a Chinese hamster lung fibroblast; HeLa S-3, an epithelial cell line from a human cervix carcinoma; CHO K-1, an epithelial cell line from a Chinese hamster ovary; and C-1300 N1E-115, a mouse neuroblastoma line. The 5-methylcytosine levels in DNA following exposure to cobalt-60 gamma radiation were measured. Induction of metallothionein in V79A03 cells and acetylcholinesterase in C-1300 N1E-115 cells after irradiation was determined and the effect of radiation on cytoplasmic and nuclear levels of DNA methyltransferase was studied and nuclear demethylase activity assayed. This study showed gamma radiation resulted in a decrease of 5-methylcytosine levels in the DNA of cultured mammalian cells. This radiation-induced hypomethylation resulted in the induction of acetylcholinesterase in mouse neuroblastoma cells and metallothionein in Chinese hamster lung fibroblasts and was caused by a decrease in DNA methyltransferase activity in the nucleus after irradiation and not by the presence of DNA demethylase

Depression and its impact on health-related quality of life among Chinese inpatients with lung cancer.

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Gu, Wen; Xu, Yan-Min; Zhu, Jun-Hong; Zhong, Bao-Liang

2017-12-01

Depression is of great concern for patients with cancer. A detailed epidemiological profile of depression in Chinese patients with lung cancer and whether depression impacts patients' health-related quality of life (HRQOL) remain unknown. This study examined the prevalence and socio-demographic and clinical correlates of depression and its effect on HRQOL in Chinese inpatients with lung cancer of two large general hospitals. A total of 148 inpatients were consecutively recruited, and administered with a standardized questionnaire to collect socio-demographic and clinical data. Depression and HRQOL were assessed with the Hospital Anxiety and Depression Scale and World Health Organization QOL Scale Brief Version, respectively. As high as 43.2% Chinese inpatients with lung cancer had clinically significant depressive symptoms. Multiple logistic regression found that depression was significantly associated with moderate-to-severe pain (OR: 4.43), metastatic cancer (OR: 3.63), a short duration after cancer diagnosis (OR: 1.04), poor performance status (OR: 3.41), and small-cell cancer (OR: 4.52). Depressed patients had significantly poorer HRQOL than not depressed patients in terms of all four domains of HRQOL. After controlling for the potential confounding effects of socio-demographic and clinical factors with analysis of covariance, these group-differences in physical (F = 29.074, P environmental (F = 27.685, P assessment and treatment, should be routinely provided in oncology departments of Chinese general hospitals.

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

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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. Copyright © 2012 Elsevier Inc. All rights reserved.

Radiation equivalence of genotoxic chemicals - Validation in cultered mammalian cell lines

International Nuclear Information System (INIS)

Murthy, M.S.S.

1982-01-01

Published data on mutations induced by ionizing radiation and 6 monofunctional alkylating agents, namely EMS, MMS, ENNG, MNNG, ENU and MNU, in different cell lines (Chinese hamster ovary, Chinese hamster lung V79, mouse lymphoma L5178 and human cells) were analysed so that radiation-equivalent chemical (REC) values could be calculated. REC values thus obtained for a given alkylating agent with different cell lines fall within a narrow range suggesting its validation in cultured mammalian cell systems including human. (orig.)

Dosimetry of inhaled plutonium-239 dioxide in rodent lung: a morphometric study

International Nuclear Information System (INIS)

Rhoads, K.

1979-06-01

Morphometric analysis of rat and hamster lung did not demonstrate any extensive changes in lung composition or structure following inhalation exposure to 239 Pu0 2 at levels near that for maximum tumor yield in rats. The problem of dosimetry for this compound thus appears to be relatively uncomplicated by any major radiation-induced pathological alterations in the lung. Rat and hamster lung were found to be similar in structure and composition, with few significant differences which could be directly related to the different tumor responses. The distribution of 239 Pu0 2 particles was not uniform in all regions of the lung; thus estimation of the dose to specific tissues or regions within the lung requires a correction for this effect. Species differences were found for particle distribution in the subpleural region and major airways, and in the spatial association of particles, both of which may affect the tumor development process. These regions contain the principal target cells for tumor production and serve as foci for the origin of tumors. Different dose distributions within these regions may therefore explain, at least in part, the difference in tumor response to inhaled 239 Pu0 2 for rats and hamsters

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

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Natarajan, Adayapalam T., E-mail: natarajan@live.nl [University of Tuscia, Viterbo (Italy); Palitti, Fabrizio [University of Tuscia, Viterbo (Italy); Hill, Mark A. [CRUK/MRC Gray Institute for Radiation Oncology and Biology, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ (United Kingdom); MRC Radiation and Genome Stability Unit, Harwell, Oxfordshire OX11 0RD (United Kingdom); Stevens, David L. [MRC Radiation and Genome Stability Unit, Harwell, Oxfordshire OX11 0RD (United Kingdom); Ahnstroem, Gunnar [Department of Microbiology and Genetic Toxicology, Stockholm University, Stockholm (Sweden)

2010-09-10

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.

Aligned, isotropic and patterned carbon nanotube substrates that control the growth and alignment of Chinese hamster ovary cells

Energy Technology Data Exchange (ETDEWEB)

Abdullah, Che Azurahanim Che; Asanithi, Piyapong; Brunner, Eric W; Jurewicz, Izabela; Bo, Chiara; Sear, Richard P; Dalton, Alan B [Department of Physics and Surrey Materials Institute, University of Surrey, Guildford, Surrey GU2 7XH (United Kingdom); Azad, Chihye Lewis; Ovalle-Robles, Raquel; Fang Shaoli; Lima, Marcio D; Lepro, Xavier; Collins, Steve; Baughman, Ray H, E-mail: r.sear@surrey.ac.uk [Alan G MacDiarmid NanoTech Institute, The University of Texas at Dallas, Richardson, TX 75080-3021 (United States)

2011-05-20

Here we culture Chinese hamster ovary cells on isotropic, aligned and patterned substrates based on multiwall carbon nanotubes. The nanotubes provide the substrate with nanoscale topography. The cells adhere to and grow on all substrates, and on the aligned substrate, the cells align strongly with the axis of the bundles of the multiwall nanotubes. This control over cell alignment is required for tissue engineering; almost all tissues consist of oriented cells. The aligned substrates are made using straightforward physical chemistry techniques from forests of multiwall nanotubes; no lithography is required to make inexpensive large-scale substrates with highly aligned nanoscale grooves. Interestingly, although the cells strongly align with the nanoscale grooves, only a few also elongate along this axis: alignment of the cells does not require a pronounced change in morphology of the cell. We also pattern the nanotube bundles over length scales comparable to the cell size and show that the cells follow this pattern.

Lung injury-dependent oxidative status and chymotrypsin-like activity of skeletal muscles in hamsters with experimental emphysema

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Tonon Jair

2013-01-01

Full Text Available Abstract Background Peripheral skeletal muscle is altered in patients suffering from emphysema and chronic obstructive pulmonary disease (COPD. Oxidative stress have been demonstrated to participate on skeletal muscle loss of several states, including disuse atrophy, mechanical ventilation, and chronic diseases. No evidences have demonstrated the occurance in a severity manner. Methods We evaluated body weight, muscle loss, oxidative stress, and chymotrypsin-like proteolytic activity in the gastrocnemius muscle of emphysemic hamsters. The experimental animals had 2 different severities of lung damage from experimental emphysema induced by 20 mg/mL (E20 and 40 mg/mL (E40 papain. Results The severity of emphysema increased significantly in E20 (60.52 ± 2.8, p Conclusions Taken together, the results of the present study suggest that muscle atrophy observed in this model of emphysema is mediated by increased muscle chymotrypsin-like activity, with possible involvement of oxidative stress in a severity-dependent manner.

Enhanced malignant transformation is accompanied by increased survival recovery after ionizing radiation in Chinese hamster embryo fibroblasts

International Nuclear Information System (INIS)

Boothman, D.A.

1994-01-01

Transformed Chinese hamster embryo fibroblasts (CHEF), which gradually increase in tumor-forming ability in nude mice, were isolated from normal diploid CHEF/18 cells. Transformed CHEF cells (i.e., T30-4 > 21-2M3 > 21-2 > normal CHEF/18) showed gradual increases in potentially lethal damage (PLD) survival recovery. β-Lapachone and camptothecin, modulators of topoisomerase I (Topo I) activity, not only prevented survival recovery in normal as well as in tumor cells, but enhanced unscheduled DNA synthesis. These seemingly conflicting results are due to the fact that Topo I activity can be modulated by inhibitors to convert single-stranded DNA lesions into double-stranded breaks. Increases in unscheduled DNA synthesis may result from a continual supply of free ends, on which DNA repair processes may act. Altering Topo I activity with modulators appears to increase X-ray lethality via a DNA lesion modification suicide pathway. Cells down-regulate Topo I immediately after ionizing radiation to prevent Topo I-mediated lesion modification and to enhance survival recovery. 16 refs., 3 figs., 1 tab

Elastatinal and leupeptin: effects on u.v.-induced mutation and sister-chromatid exchanges in Chinese hamster cells

International Nuclear Information System (INIS)

Paul, P.; Fujiwara, Y.

1981-01-01

Microbial protease inhibitors elastatinal and leupeptin were tested for cytotoxicity and for effects on spontaneous and u.v.-induced 6-thioguanine-resistant (6TGsup(r)) mutation and sister-chromatid exchange (SCE) in V79 Chinese hamster cells. Continuous treatment with elastatinal exhibited marked cytotoxicity, while leupeptin was almost non-cytotoxic. Elastatinal rapidly induced cytotoxic effects as a function of its concentration and time of exposure. Near maximum cytotoxicity was reached after exposures of 6-8 h and this was partially abolished by the presence of 2.5 μg cycloheximide per ml. Concentrations of either protease inhibitor which gave 60-80% survival had no appreciable effects on u.v. survival and frequencies of spontaneous and u.v.-induced 6TGsup(r) mutation and SCE. However, reconstruction experiments revealed that pretreatments of 6TGsup(r) and 6TGsup(s) (wild-type) cells with these inhibitors for 6 days tended to block metabolic co-operation in their co-cultures. Thus, elastatinal and leupeptin are neither clastogenic nor mutagenic by themselves, and do not alter mutation fixation and expression. (author)

Elastatinal and leupeptin: effects on u.v.-induced mutation and sister-chromatid exchanges in Chinese hamster cells

International Nuclear Information System (INIS)

Paul, P.; Fujiwara, Y.

1981-01-01

Microbial protease inhibitors elastatinal and leupeptin were tested for cytotoxicity and for effects on spontaneous and u.v.-induced 6-thioguanine-resistant (6TGr) mutation and sister-chromatid exchange (SCE) in V79 Chinese hamster cells. Continuous treatment with elastatinal exhibited marked cytotoxicity, while leupeptin was almost non-cytotoxic. Elastatinal rapidly induced cytotoxic effects as a function of its concentration and time of exposure. Near maximum cytotoxicity was reached after exposure of 6-8 h and this was partially abolished by the presence of 2.5 micrograms cycloheximide per ml. Concentrations of either protease inhibitor which gave 60-80% survival had no appreciable effects on u.v. survival and frequencies of spontaneous and u.v.-induced 6TGr mutation and SCE. However, reconstruction experiments revealed that pretreatments of 6TGr and 6TGs (wild-type) cells with these inhibitors for 6 days tended to block metabolic co-operation in their co-cultures. Thus, elastatinal and leupeptin are neither clastogenic mutagenic by themselves, and do not alter mutation fixation and expression

Distinct functional characteristics of levocabastine sensitive rat neurotensin NT2 receptor expressed in Chinese hamster ovary cells.

Science.gov (United States)

Yamada, M; Yamada, M; Lombet, A; Forgez, P; Rostène, W

1998-01-01

Neurotensin has been shown to produce pharmacological effects both in brain and periphery. Several of these effects are mediated by a high-affinity neurotensin NT1 receptor. On the other hand, a low-affinity levocabastine-sensitive neurotensin NT2 receptor was molecularly cloned from rodent brain recently. In this study, in contrast to NT1 receptor, levocabastine (a histamine H1 receptor antagonist) and SR48692 (an antagonist for NT1 receptor) strongly stimulated intracellular Ca2+ mobilization in transfected Chinese hamster ovary cells expressing rat NT2 receptor, thus acting as potent NT2 receptor. Furthermore, despite of their affinities for NT2 receptor, the Ca2+ responses to potent NT1 agonists, neurotensin or JMV449 ([Lys8-(CH2NH)-Lys9]Pro-Tyr-Ile-Leu, a peptidase resistant analogue of neurotensin) were much smaller than that observed with SR48692. These findings suggest that NT1 and NT2 receptors present distinct functional characteristics and that SR48692 may act as a potent agonist for NT2 receptor.

Interaction between the effects of pepleomycin with lidocaine and radiation on cultured Chinese hamster V79 cells

International Nuclear Information System (INIS)

Shimada, Yuji

1989-01-01

The interaction of the cytotoxicities in combination use of lidocaine (LID), pepleomycin (PEP) and radiation in combined treatment was studied using Chinese hamster V79 cells by colony forming assay. LID showed no cytotoxic effect up to 12 mM when it was employed alone. However selective enhancement of the PEP cytotoxic effect appeared when the drugs were used simultaneously. The mechanism of this enhancing effect was thought to involve inhibition by LID of the repair of the cells from PEP potentially lethal damage. LID showed no enhancing effect on the radiation cytotoxicity when the agents were used simultaneously. Only an additive effect appeared when PEP and radiation were employed simultaneously. An interactive effect appeared when LID, PEP and radiation were used simultaneously, although this effect was not so significant. The enhancement ratio of PEP with LID on radiation was 1.58. The fundamental mechanism of enhancement of cytotoxic effect of LID on PEP and the interactive relationship among LID, PEP and radiation are analyzed and discussed. (author)

Similar kinetics of chromatid aberrations in X-irradiated xrs 5 and wild-type Chinese hamster ovary cells

International Nuclear Information System (INIS)

MacLeod, R.A.F.; Bryant, P.E.

1990-01-01

We have studied the kinetics of chromatid aberrations in cells of the Chinese hamster ovary (CHO-K1) derived, X-ray sensitive cell line xrs 5 irradiated in the G 2 phase at 37 0 C, as well as during a cell cycle extended by transient hypothermia at 33 0 C. While a given X-ray dose was estimated to produce about 4 times as many chromatid break and twice the frequency of exchanges in xrs 5 cells as in the parent line, there was no difference between the lines in the rates of disappearance of chromatid breaks during G 2 at either temperature; and similar patterns of chromatid exchange kinetics were observed in the two lines. Both the frequencies and distributions of chromatid breaks at different times after irradiation are consistent with the view that the disappearance of these during incubation represents a repair process. These results imply that the G 2 chromosomal radiosensitivity of the xrs 5 mutant resides at the level of initial chromatid damage. (author)

Indoor Air Pollution and Risk of Lung Cancer among Chinese Female Non-Smokers

Science.gov (United States)

Mu, Lina; Liu, Li; Niu, Rungui; Zhao, Baoxing; Shi, Jianping; Li, Yanli; Scheider, William; Su, Jia; Chang, Shen-Chih; Yu, Shunzhang; Zhang, Zuo-Feng

2013-01-01

Purpose To investigate indoor particulate matter (PM) level and various indoor air pollution exposure, and to examine their relationships with risk of lung cancer in an urban Chinese population, with a focus on non-smoking women. Methods We conducted a case-control study in Taiyuan, China, consisting of 399 lung cancer cases and 466 controls, of which 164 cases and 218 controls were female non-smokers. Indoor PM concentrations, including PM1, PM2.5, PM7, PM10 and TSP, were measured using a particle mass monitor. Unconditional logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals after adjusting for age, education, annual income and smoking. Results Among non-smoking women, lung cancer was strongly associated with multiple sources of indoor air pollution 10 years ago, including heavy exposure to ETS at work (aOR=3.65), high frequency of cooking (aOR=3.30), and solid fuel usage for cooking (aOR=4.08) and heating (aORcoal stove=2.00). Housing characteristics related to poor ventilation, including single-story, less window area, no separate kitchen, no ventilator and rarely having windows open, are associated with lung cancer. Indoor medium PM2.5 concentration was 68ug/m3, and PM10 was 230ug/m3. PM levels in winter are strongly correlated with solid fuel usage for cooking, heating and ventilators. PM1 levels in cases are more than 3-time higher than that in controls. Every 10 ug/m3 increase in PM1 is associated with 45% increased risk of lung cancer. Conclusions Indoor air pollution plays an important role in the development of lung cancer among non-smoking Chinese women. PMID:23314675

Irradiation of the lung with static plutonium microemboli

International Nuclear Information System (INIS)

Holland, L.M.; Prine, J.R.; Smith, D.M.; Anderson, E.C.

1975-01-01

Syrian hamsters are exposed to selected lung burdens of plutonium-239 contained in 10-μm diameter microspheres of ZrO 2 ceramic. After injection into the jugular vein, the microspheres lodge in the lung capillaries and remain immobile throughout the lifetime of the animal. The specific activity of the microspheres is varied from 0.22 to 59 pCi/sphere, and the lung burdens achieved vary from 0.44 to 354 nCi. The distribution in the lung is essentially random except in the groups receiving high numbers of spheres. Since entrapment in the lung approaches 100 percent, there is essentially none of the involvement of other organs seen with inhalation methods. Hamsters are also exposed intratracheally to 210 Po to compare the results from an experiment in which other organs are involved and in which a high tumor yield may be anticipated. Tumor production in the microemboli experiment has been quite low, and the overall damage to the lung has been minimal in comparison to the intratracheal experiments with 210 Po or with published data from aerosol experiments. (auth)

DNA conformation of Chinese hamster V79 cells and sensitivity to ionizing radiation

International Nuclear Information System (INIS)

Olive, P.L.; Hilton, J.; Durand, R.E.

1986-01-01

Chinese hamster V79 cells grown for 20 h in suspension culture form small clusters of cells (spheroids) which are more resistant to killing by ionizing radiation than V79 cells grown as monolayers. This resistance appears to be due to the greater capacity of cells grown in contact to repair radiation damage. Attempts to relate this ''contact effect'' to differences in DNA susceptibility or DNA repair capacity have provided conflicting results. Two techniques, alkaline sucrose gradient sedimentation and alkaline elution, show no difference in the amounts of radiation-induced DNA single-strand breakage or its repair between suspension or monolayer cells. However, using the alkali-unwinding assay, the rate of DNA unwinding is much slower for suspension cells than for monolayer cells. Interestingly, a decrease in salt concentration or in pH of the unwinding solution eliminates these differences in DNA unwinding kinetics. A fourth assay, sedimentation of nucleoids on neutral sucrose gradients, also shows a significant decrease in radiation damage produced in suspension compared to monolayer cultures. It is believed that this assay measures differences in DNA conformation (supercoiling) as well as differences in DNA strand breakage. We conclude from these four assays that the same number of DNA strand breaks/Gy is produced in monolayer and spheroid cells. However, changes in DNA conformation or packaging occur when cells are grown as spheroids, and these changes are responsible for reducing DNA damage by ionizing radiation

Vomeronasal organ lesion disrupts social odor recognition, behaviors and fitness in golden hamsters.

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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. © 2013 International Society of Zoological Sciences, Institute of Zoology/Chinese Academy of Sciences and Wiley Publishing Asia Pty Ltd.

Respiratory health and lung function in Chinese restaurant kitchen workers.

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Wong, Tze Wai; Wong, Andromeda H S; Lee, Frank S C; Qiu, Hong

2011-10-01

To measure air pollutant concentrations in Chinese restaurant kitchens using different stove types and assess their influence on workers' respiratory health. 393 kitchen workers from 53 Chinese restaurants were surveyed over 16 months: 115 workers from 21 restaurants using only electric stoves and 278 workers from 32 restaurants using only gas stoves. Workers were interviewed about their respiratory symptoms and had their lung function tested. Concentrations of nitric oxide (NO), nitrogen dioxide (NO(2)), carbon monoxide (CO), carbon dioxide (CO(2)), methane (CH(4)), non-methane hydrocarbons (NMHC), total volatile organic compounds (TVOC) and fine particulate matter (PM(2.5)) were measured using portable monitors and air-bag sampling. Temperature and noise levels were assessed. Median concentrations of NO, NO(2) and CO were 7.4, 1.5 and 1.6 times higher in gas-fuelled kitchens than in electric ones and average concentrations of PM(2.5) and TVOC were 81% and 78% higher, respectively. Differences were smaller for CH(4) and NMHC. Electricity-run kitchens were 4.5°C cooler and 9 dBA less noisy than gas-fuelled ones. Workers using electric cookers had significantly better lung function than their gas-using counterparts and their mean FEV(1) and FVC values were 5.4% and 3.8% higher, respectively, after adjustment for confounders. Wheeze, phlegm, cough and sore throat were more prevalent in workers using gas. The adjusted OR for having phlegm regularly was significantly higher. The poorer lung function and higher prevalence of respiratory symptoms among workers in gas-fuelled kitchens compared to those in electricity-powered kitchens may be associated with exposure to higher concentrations of toxic air pollutants generated during gas cooking.

Detection of anti-aquaporin-4 autoantibodies in the sera of Chinese neuromyelitis optica patients

Institute of Scientific and Technical Information of China (English)

Miao Li; Weiheng Su; Jie Wang; Francesco Pisani; Antonio Frigeri; Tonghui Ma

2013-01-01

In this study, we recruited 10 neuromyelitis optica patients, two multiple sclerosis patients and two myelitis patients. Chinese hamster lung fibroblast (V79) cells transfected with a human aquaporin-4-mCherry fusion protein gene were used to detect anti-aquaporin-4 antibody in neuromyelitis optica patient sera by immunofluorescence. Anti-aquaporin-4 autoantibody was stably detected by immunofluorescence in neuromyelitis optica patient sera exclusively. The sensitivity of the assay for neuromyelitis optica was 90% and the specificity for neuromyelitis optica was 100%. The anti-aquaporin-4 antibody titers in sera were tested with serial dilutions until the signal disappeared. A positive correlation was detected between Expanded Disability Status Scale scores and serum anti-aquaporin-4 antibody titers. The anti-aquaporin-4 antibody assay is highly sensitive and specific in the sera of Chinese neuromyelitis optica patients. Detection of aquaporin-4 autoantibody is important for the diagnosis and treatment of neuromyelitis optica.

Detection of anti-aquaporin-4 autoantibodies in the sera of Chinese neuromyelitis optica patients.

Science.gov (United States)

Li, Miao; Su, Weiheng; Wang, Jie; Pisani, Francesco; Frigeri, Antonio; Ma, Tonghui

2013-03-15

In this study, we recruited 10 neuromyelitis optica patients, two multiple sclerosis patients and two myelitis patients. Chinese hamster lung fibroblast (V79) cells transfected with a human aquaporin-4-mCherry fusion protein gene were used to detect anti-aquaporin-4 antibody in neuromyelitis optica patient sera by immunofluorescence. Anti-aquaporin-4 autoantibody was stably detected by immunofluorescence in neuromyelitis optica patient sera exclusively. The sensitivity of the assay for neuromyelitis optica was 90% and the specificity for neuromyelitis optica was 100%. The anti-aquaporin-4 antibody titers in sera were tested with serial dilutions until the signal disappeared. A positive correlation was detected between Expanded Disability Status Scale scores and serum anti-aquaporin-4 antibody titers. The anti-aquaporin-4 antibody assay is highly sensitive and specific in the sera of Chinese neuromyelitis optica patients. Detection of aquaporin-4 autoantibody is important for the diagnosis and treatment of neuromyelitis optica.

Detection of anti-aquaporin-4 autoantibodies in the sera of Chinese neuromyelitis optica patients★

Science.gov (United States)

Li, Miao; Su, Weiheng; Wang, Jie; Pisani, Francesco; Frigeri, Antonio; Ma, Tonghui

2013-01-01

In this study, we recruited 10 neuromyelitis optica patients, two multiple sclerosis patients and two myelitis patients. Chinese hamster lung fibroblast (V79) cells transfected with a human aquaporin-4-mCherry fusion protein gene were used to detect anti-aquaporin-4 antibody in neuromyelitis optica patient sera by immunofluorescence. Anti-aquaporin-4 autoantibody was stably detected by immunofluorescence in neuromyelitis optica patient sera exclusively. The sensitivity of the assay for neuromyelitis optica was 90% and the specificity for neuromyelitis optica was 100%. The anti-aquaporin-4 antibody titers in sera were tested with serial dilutions until the signal disappeared. A positive correlation was detected between Expanded Disability Status Scale scores and serum anti-aquaporin-4 antibody titers. The anti-aquaporin-4 antibody assay is highly sensitive and specific in the sera of Chinese neuromyelitis optica patients. Detection of aquaporin-4 autoantibody is important for the diagnosis and treatment of neuromyelitis optica. PMID:25206717

Association between cooking oil fume exposure and lung cancer among Chinese nonsmoking women: a meta-analysis

Directory of Open Access Journals (Sweden)

Xue Y

2016-05-01

Full Text Available Yingbo Xue, Ying Jiang, Shan Jin, Yong Li Department of Oncology, Guizhou Provincial People’s Hospital, Guiyang, Guizhou, People’s Republic of China Abstract: Lung cancer has been the main cause of cancer death around the world. Cigarette smoking has been identified as a risk factor for lung cancer in males. However, the etiological factors in nonsmoking women remain elusive. A meta-analysis was conducted to evaluate the relationship between cooking oil fume exposure and lung cancer among Chinese nonsmoking women. Thirteen articles containing three population-based case–control and ten hospital-based case–control studies were included in this meta-analysis. These studies with a total of 3,596 lung cancer women and 6,082 healthy controls were analyzed by RevMan 5.3. Fixed effects model or random effects model was used to obtain pooled estimates of risk ratio. The risk ratios with a 95% CI were 1.74 (95% CI =1.57–1.94 and 2.11 (95% CI =1.54–2.89, respectively. Cooking oil fume exposure as well as not using a kitchen ventilator when cooking was significantly associated with lung cancer among nonsmoking women (Z=10.07, P<0.00001; Z=4.65, P<0.00001. Cooking oil fume exposure, especially lacking a fume extractor, may increase the risk of lung cancer among Chinese nonsmoking women. Keywords: cooking oil fume exposure, lung cancer, meta-analysis, nonsmoking women 

Laser microirradiation of Chinese hamster cells at wavelength 365 nm: effects of psoralen and caffeine

International Nuclear Information System (INIS)

Cremer, T.; Peterson, S.P.; Cremer, C.; Berns, M.W.

1981-01-01

Cells of a V79 subline of the Chinese hamster were microirradiated at wavelength 365 nm in the presence of the psoralen derivative, trioxsalen. Microirradiation was accomplished by a pulsed argon laser microbeam either in anaphase or in interphase 3 h after mitosis. Inhibition of clonal growth and formation of micronuclei at the first postirradiation mitosis were observed after microirradiation of anaphase chromosomes and of small parts of the interphase nucleus. Microirradiation of the cytoplasm beside the interphase nucleus or between the sets of chromosomes moving apart from each other in anaphase did not produce these effects. Anaphase experiments showed that only the daughter cell which received microirradiated chromatin exhibited an abnormal growth pattern. Most interestingly, shattering of the whole chromosome complement could be induced by microirradiation of small parts of the interphase nucleus and post-treatment with caffeine. Since microirradiation of chromatin in the absence of psoralen was not effective, we consider formation of psoralen photoadducts to nucleic acids in microirradiated chromatin to be the specific cause of the effects. We suggest that DNA photolesions in chromosome segments present in the microirradiated part of the nucleus can induce shattering of all the chromosomes in the microirradiated nucleus. Several possibilities are discussed to explain this unexpected finding

Transfer of Chinese hamster DNA repair gene(s) into repair-deficient human cells (Xeroderma pigmentosum)

International Nuclear Information System (INIS)

Karentz, D.; Cleaver, J.E.

1985-01-01

Transfer of repair genes by DNA transfection into repair-deficient Xeroderma pigmentosum (XP) cells has thus far been unsuccessful, presenting an obstacle to cloning XP genes. The authors chose an indirect route to transfer repair genes in chromosome fragments. DNA repair-competent (UV resistant) hybrid cell lines were established by PEG-mediated fusions of DNA repair-deficient (UV sensitive) human fibroblasts (XP12RO) with wild type Chinese hamster (CHO) cells (AA8). CHO cells were exposed to 5 Krad X-rays prior to fusions, predisposing hybrid cells to lose CHO chromosome fragments preferentially. Repair-competent hybrids were selected by periodic exposures to UV light. Secondary and tertiary hybrid cell lines were developed by fusion of X-irradiated hybrids to XP12RO. The hybrid cell lines exhibit resistance to UV that is comparable to that of CHO cells and they are proficient at repair replication after UV exposure. Whole cell DNA-DNA hybridizations indicate that the hybrids have greater homology to CHO DNA than is evident between XP12RO and CHO. These observations indicate that CHO DNA sequences which can function in repair of UV-damaged DNA in human cells have been transferred into the genome of the repair-deficient XP12RO cells

Beschermingsplan hamster 2005-2010

NARCIS (Netherlands)

Haye, la M.J.J.; Jansman, H.A.H.

2005-01-01

Alterra-Concept van het beschermingsplan hamster 2005-2010. De hamster is in het meest westelijke deel van het Europese verspreidingsgebied bedreigd. De kennis die in de afgelopen periode is opgedaan van de hamster en de maatregelen die in het veld zijn uitgevoerd vormen de basis voor dit tweede

Inhibition and recovery of the rate of DNA synthesis in V79 Chinese hamster cells following ultraviolet light irradiation

International Nuclear Information System (INIS)

Ventura, A.M.; Meneghini, R.

1984-01-01

Chinese hamster fibroblasts (V79 cell line) exhibit the phenomenon of recovery of DNA synthesis from the initial inhibition observed after ultraviolet light irradiation, in the absence of significant excision of pyrimidine dimers. In an attempt to determine whether the initial inhibition and subsequent recovery can be accounted for by parallel variations in the rate of movement of the replication fork, the cells were pulse-labeled with radioactive bromodeoxyuridine at different times following irradiation and their DNA centrifuged in neutral CsCl density gradients. When DNA synthesis inhibition was at a maximum, an accumulation of DNA, of density intermediate between hybrid and nonsubstituted DNA, was noticed in the density-distribution profiles. The density distribution of DNA along the gradient can provide an estimate of the rate of movement of the replication fork, and the results indicate that most of the variation in the overall rate of DNA synthesis can be accounted for by a parallel variation in the rate of fork movement. (Auth.)

PLACENTAL TRANSFER AND FETAL DEPOSITION OF HEXACHLOROBENZENE IN THE HAMSTER AND GUINEA PIG

Science.gov (United States)

Hexachlorobenzene (HCB) was administered at dose levels of 0, 1.0, 10.0, or 50.0 mg HCB/kg body wt by gavage to pregnant hamsters and guinea pigs for 6 days up to the time of liver development in the fetus. Samples of maternal fat, thymus, skin, liver, lung, brain, spleen, urinar...

Mechanism of resistance of noncycling mammalian cells to 4'-(9-acridinylamino)methanesulfon-m-anisidide: comparison of uptake, metabolism, and DNA breakage in log- and plateau-phase Chinese hamster fibroblast cell cultures

International Nuclear Information System (INIS)

Robbie, M.A.; Baguley, B.C.; Denny, W.A.; Gavin, J.B.; Wilson, W.R.

1988-01-01

Resistance of noncycling cells to amsacrine (m-AMSA) has been widely reported and may limit the activity of this drug against solid tumors. The biochemical mechanism(s) for this resistance have been investigated using spontaneously transformed Chinese hamster fibroblasts (AA8 cells, a subline of Chinese hamster ovary-cells) in log- and plateau-phase spinner cultures. In early plateau phase most cells entered a growth-arrested state with a G1-G0 DNA content and showed a marked decrease in sensitivity to cytotoxicity induced by a 1-h exposure to m-AMSA or to its solid tumor-active analogue, CI-921. Studies with radiolabeled m-AMSA established that similar levels of drug were accumulated by log- and plateau-phase cells and that there was no significant drug metabolism in either of these cultures after 1 h. However, marked differences in sensitivity to m-AMSA-induced DNA breakage were observed using a fluorescence assay for DNA unwinding. Changes in sensitivity to DNA breakage occurred in parallel with changes in sensitivity to m-AMSA-induced cell killing. DNA breaks disappeared rapidly after drug removal (half-time approximately 4 min), suggesting that these lesions were probably mediated by DNA topoisomerase II. Resistance to m-AMSA may therefore be associated with changes in topoisomerase II activity in noncycling cells

Regional assignment of seven genes on chromosome 1 of man by use of man-Chinese hamster somatic cell hybrids. I. Results obtained after hybridization of human cells carrying reciprocal translocations involving chromosome 1.

Science.gov (United States)

Jongsma, A P; Burgerhout, W G

1977-01-01

Regional localization studies of genes coding for human PGD, PPH1, PGM1, UGPP, GuK1, Pep-C, and FH, which have been assigned to chromosome 1, were performed with man-Chinese hamster somatic cell hybrids, Informative hybrids that retained fragments of the human chromosome 1 were produced by fusion of hamster cells with human cells carrying reciprocal translocations involving chromosome 1. Analysis of the hybrids that retained one of the translocation chromosomes or de novo rearrangements involving the human 1 revealed the following gene positions: PGD and PPH1 in 1pter leads to 1p32, PGM1 in 1p32 leads to 1p22, UGPP and GuK1 in 1q21 leads to 1q42, FH in 1qter leads to 1q42, and Pep-C probably in 1q42.

In vivo mutagenicity studies in rats mice and Chinese hamsters fed irradiated foodstuffs - chicken, fish, dates, pulses, mangoes and cocoa beans

International Nuclear Information System (INIS)

Renner, H.W.

1982-01-01

Three in vivo genetic toxicity tests were performed in rats, mice and Chinese hamsters to detect possible mutagenic effects of irradiated chicken, dried dates, fish, cocoa beans, pulses and mangoes. The tests employed were the micronucleus test and sister-chromatid exchange (SCE) test for irradiated and unirradiated samples of all foodstuffs listed, and the spermatogonia test, (including SCE technique) in mice for irradiated and unirradiated chicken, fish and dates only. In the case of cocoa beans, the mutagenicity tests were performed on an additional test group fed beans fumigated with ethylene oxide. The different mammalian species used for the various experiments are given below. None of the tests provided any evidence of mutagenicity induced by irradiation in any of the foodstuffs studied. Moreover, these tests are currently considered to be the most sensitive in vivo mutagenicity tests in mammals. (orig.)

Yield of chromosomal aberrations and recoil particle range in Chineses hamster fibroblasts exposed to 8.5 to 500 keV neutrons

International Nuclear Information System (INIS)

Sturelid, S.; Bergman, R.

1976-01-01

Induction of chromatid aberrations in S-phase Chinese hamster fibroblasts has been studied for irradiation by 60 Co gamma rays and neutrons of average energy 8.5, 45, 83, 200 and 500 keV. At 10 per cent aberration level the relative biological afficiency varied between 2.2 +- 0.6 (at 8.5 keV) and a maximum of 47 +- 9 (at 200 keV). The neutron generated recoils have short range in comparison to chromosomal dimensions. The strong variation with neutron energy is therefore not necessarily reflecting variations in the average linear energy transfer. Good agreement between experimental and predicted response was obtained when effects ascribed to range were considered. A critical volume within which primary lesions should occur in order to make chromosomal aberrations probable was derived. The corresponding site radius was estimated to be 1-3 μm. (author)

Examination of Chronic Smoking Behavior and Eligibility for Low-Dose Computed Tomography for Lung Cancer Screening Among Older Chinese Male Smokers.

Science.gov (United States)

Li, Chien-Ching; Matthews, Alicia K; Dong, XinQi

2017-07-01

Low-dose computed tomography lung cancer (LDCT) screening is an effective way to decrease lung cancer mortality. Both Medicare and private insurers offer coverage of LDCT screening to beneficiaries who are at high risk of developing lung cancer. In this study, we examined rates and predictors of chronic smoking behavior and eligibility for coverage of LDCT screening among older Chinese men living in the greater Chicago area. Data were obtained from the Population Study of Chinese Elderly in Chicago, a population-based survey of community-dwelling, older Chinese adults in the Chicago metropolitan area. Eligibility criteria according to Centers of Medicare and Medicaid Services (CMS) and U.S. Preventive Services Task Force (USPSTF) for LDCT screening were used. Multivariate logistic regression was conducted to determine predictors of chronic smoking behavior which was operationalized as meeting criteria for LDCT screening. A quarter of the sample were current smokers and 42.5% reported a prior history of smoking. Eighteen percent and 22% of older Chinese men met the eligibility criteria for appropriateness for CMS and USPSTF LDCT screening, respectively. Furthermore, education, marital status, and number of children were significantly associated with chronic smoking behavior. Older Chinese men with chronic smoking behavior are at high risk of developing lung cancer and nearly one in five meet eligibility for LDCT screening. Increased outreach and education regarding early detection of lung cancer and smoking cessation are needed for this vulnerable and high-risk population. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Use of the α-mannosidase I inhibitor kifunensine allows the crystallization of apo CTLA-4 homodimer produced in long-term cultures of Chinese hamster ovary cells

International Nuclear Information System (INIS)

Yu, Chao; Crispin, Max; Sonnen, Andreas F.-P.; Harvey, David J.; Chang, Veronica T.; Evans, Edward J.; Scanlan, Christopher N.; Stuart, David I.; Gilbert, Robert J. C.; Davis, Simon J.

2011-01-01

The α-mannosidase I inhibitor kifunensine inhibited N-glycan processing in long-term cultures of Chinese hamster ovary cells, allowing deglycosylation and crystallization of the homodimeric extracellular region of the inhibitory glycoprotein receptor CTLA-4 (CD152). Glycoproteins present problems for structural analysis since they often have to be glycosylated in order to fold correctly and because their chemical and conformational heterogeneity generally inhibits crystallization. It is shown that the α-mannosidase I inhibitor kifunensine, which has previously been used for the purpose of glycoprotein crystallization in short-term (3–5 d) cultures, is apparently stable enough to be used to produce highly endoglycosidase H-sensitive glycoprotein in long-term (3–4 week) cultures of stably transfected Chinese hamster ovary (CHO) cells. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry-based analysis of the extracellular region of the cytotoxic T-lymphocyte antigen 4 (CTLA-4; CD152) homodimer expressed in long-term CHO cell cultures in the presence of kifunensine revealed that the inhibitor restricted CTLA-4 glycan processing to Man 9 GlcNAc 2 and Man 5 GlcNAc 2 structures. Complex-type glycans were undetectable, suggesting that the inhibitor was active for the entire duration of the cultures. Endoglycosidase treatment of the homodimer yielded protein that readily formed orthorhombic crystals with unit-cell parameters a = 43.9, b = 51.5, c = 102.9 Å and space group P2 1 2 1 2 1 that diffracted to Bragg spacings of 1.8 Å. The results indicate that kifunensine will be effective in most, if not all, transient and long-term mammalian cell-based expression systems

Induction of DNA-protein cross-linking in Chinese hamster cells by monochromatic 365 and 405 NM ultraviolet light

International Nuclear Information System (INIS)

Han, A.; Peak, M.J.; Peak, J.G.

1984-01-01

The survival, the induction of DNA-protein cross-linking, and the number of T4-endonuclease sensitive sites were measured in Chinese hamster cells that had been irradiated with 365 and 405 nm monochromatic light. The survival measurements show that cells are somewhat less sensitive to 405 nm light than to 365 nm light. The difference is expressed predominantly in the shoulder widths of the survival curves, whereas the slopes of the two curves are about the same. Induction of pyrimidine dimers, as indicated by the number of endonuclease-sensitive sites, after exposures that produce about 10% survival is very low at 365 nm (approx. 4 endonuclease sites per 2 x 10 8 daltons), while no dimers are detected at 405 nm. In contrast, DNA-protein cross-links are induced rather effectively at either wavelength even after exposures that result in a relatively high survival (60-20%). These measurements support the conclusion that lethality in mammalian cells after irradiations with 365 or 405 nm light is caused by a nondimer damage, possibly DNA-protein cross-links. (author)

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

International Nuclear Information System (INIS)

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. 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

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

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Araújo Maria Cristina P.

1999-01-01

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.

Response of the microtubular cytoskeleton following hyperthermia as a prognostic indicator of survival of Chinese hamster ovary cells

International Nuclear Information System (INIS)

Coss, Ronald A.; Alden, Mark E.; Wachsberger, Phyllis R.; Smith, Nancy N.

1996-01-01

Purpose: The response of the microtubular (MT) cytoskeleton to hyperthermia was assessed as a prognostic indicator of cytotoxicity. Methods and Materials: Heat-induced collapse and subsequent recovery of the MT system were compared with survival for both nonthermotolerant (NT) and thermotolerant (TT) G1 populations of Chinese hamster ovary (CHO) cells. The response of the MT system was monitored using immunofluorescence staining. The G1 populations of NT and TT cells were heated by submersion in 45.0 and 43.0 deg. C waterbaths. Results: Heat-induced perinuclear collapse of the MT system did not correlate with survival for the NT and TT populations. However, recovery of the organization of the MT cytoskeleton was correlatable with survival. The regression line of survival plotted as a function of MT recovery is fit by: y = -0.43 + 1.03x, r 2 = 0.95 (p < 0.0005). Conclusion: Restoration of the organization of the MT cytoskeleton following hyperthermia may be used as a prognostic indicator of survival of CHO cells heated in G1

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

International Nuclear Information System (INIS)

Nelson, J.M.; Metting, N.F.; Braby, L.A.; Roesch, W.C.

1987-01-01

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

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

Relative biological efficiency of intermediate energy neutrons and 60Co rays for induction of chromosomal aberrations in Chinese hamster fibroblasts

International Nuclear Information System (INIS)

Sturelid, S.; Bergman, R.

1976-01-01

Intermediate energy neutrons are unique in that a considerable fraction of critical interactions and of dose absorbed is not associated with ionization but with atomic collision. It is still unknown to what extent the qualitative difference in primary damage after atomic collision compared to that of ionization and excitation becomes expressed at biological levels. Chromosomal aberrations were studied in Chinese hamster fibroblasts exposed for 5-8 hours at 22 degree C to intermediate energy neutrons, mean energy 8.5 keV, or to 60 Co-gamma rays. RBE at the 10 per cent aberration frequency level in S-phase were 2.2+-0.6 for total aberrations, 2.1+-0.6 for chromatid breaks and 1.8+-0.5 for exchanges. For each chromatid aberration observed after recovery, about 200 bondbreaking atomic collisions besides 3000 primary iniozations should have occured in DNA. However, the extent to which the aberration response is due to atomic collisions is not clear. (author)

Effect of arsenite on the DNA repair of UV-irradiated Chinese hamster ovary cells

International Nuclear Information System (INIS)

Lee-Chen, S.F.; Yu, C.T.; Jan, K.Y.

1992-01-01

Arsenite, an ubiquitous human carcinogen, has been shown to enhance the cytotoxicity, mutagenicity and clastogenicity of UV light in mammalian cells. Arsenite may exert its co-genotoxic effects by inhibiting DNA repair. Results from alkaline sucrose gradient sedimentation show that arsenite did not accumulate UV-induced DNA strand breaks in Chinese hamster ovary (CHO) K1 cells as aphidicolin plus hydroxyurea (HU) did. These data indicate that arsenite did not inhibit the activity of DNA polymerase α in UV repair. Treatment with arsenite before UV irradiation slightly reduced the DNA strand breaks accumulated by cytosine β-D-arabinofuranoside (AraC) plus HU. This effect implies that arsenite only slightly inhibited the incision of UV-induced DNA adducts. The low molecular weight DNA accumulated by post-UV incubation with AraC plus HU shifted to high molecular weight upon the incubation of cells in drug-free medium, but this shifting was prohibited by the presence of arsenite. This suggests that arsenite inhibited the rejoining of DNA strand breaks. When a pulse-chase labelling procedure was applied on UV-irradiated cells, the chain elongation of nascent DNA was strongly inhibited by post-incubation with arsenite. These data show that arsenite inhibited post-replication repair in UV-irradiated cells. Therefore, the steps inhibited by arsenite in UV-induced cells. Therefore, the steps inhibited by arsenite in UV-induced DNA repair in CHO K1 cells are different from human fibroblasts. (author)

Effect of arsenite on the DNA repair of UV-irradiated Chinese hamster ovary cells

Energy Technology Data Exchange (ETDEWEB)

Lee-Chen, S.F.; Yu, C.T.; Jan, K.Y. (Academia Sinica, Taipei, (Taiwan). Institute of Zoology)

1992-01-01

Arsenite, an ubiquitous human carcinogen, has been shown to enhance the cytotoxicity, mutagenicity and clastogenicity of UV light in mammalian cells. Arsenite may exert its co-genotoxic effects by inhibiting DNA repair. Results from alkaline sucrose gradient sedimentation show that arsenite did not accumulate UV-induced DNA strand breaks in Chinese hamster ovary (CHO) K1 cells as aphidicolin plus hydroxyurea (HU) did. These data indicate that arsenite did not inhibit the activity of DNA polymerase [alpha] in UV repair. Treatment with arsenite before UV irradiation slightly reduced the DNA strand breaks accumulated by cytosine [beta]-D-arabinofuranoside (AraC) plus HU. This effect implies that arsenite only slightly inhibited the incision of UV-induced DNA adducts. The low molecular weight DNA accumulated by post-UV incubation with AraC plus HU shifted to high molecular weight upon the incubation of cells in drug-free medium, but this shifting was prohibited by the presence of arsenite. This suggests that arsenite inhibited the rejoining of DNA strand breaks. When a pulse-chase labelling procedure was applied on UV-irradiated cells, the chain elongation of nascent DNA was strongly inhibited by post-incubation with arsenite. These data show that arsenite inhibited post-replication repair in UV-irradiated cells. Therefore, the steps inhibited by arsenite in UV-induced cells. Therefore, the steps inhibited by arsenite in UV-induced DNA repair in CHO K1 cells are different from human fibroblasts. (author).

Mutagenicity and antimutagenicity of Baccharis dracunculifolia extract in chromosomal aberration assays in Chinese hamster ovary cells.

Science.gov (United States)

Munari, Carla Carolina; Resende, Flávia Aparecida; Alves, Jacqueline Morais; de Sousa, João Paulo; Bastos, Jairo Kenupp; Tavares, Denise Crispim

2008-09-01

Baccharis dracunculifolia De Candole (Asteraceae), a native plant from the Brazilian "cerrado", is widely used in folk medicine as an anti-inflammatory agent and for the treatment of gastrointestinal diseases. B. dracunculifolia has been described as the most important plant source of propolis in southeastern Brazil, which is called green propolis due to its color. The aim of the present study was to evaluate the mutagenic and antimutagenic effects of the ethyl acetate extract of B. dracunculifolia leaves (Bd-EAE) on Chinese hamster ovary cells. On one hand, the results showed a significant increase in the frequencies of chromosome aberrations at the highest Bd-EAE concentration tested (100 microg/mL). On the other hand, the lowest Bd-EAE concentration tested (12.5 micro/mL) significantly reduced the chromosome damage induced by the chemotherapeutic agent doxorubicin. The present results indicate that Bd-EAE has the characteristics of a so-called Janus compound, that is, Bd-EAE is mutagenic at higher concentrations, whereas it displays a chemopreventive effect on doxorubicin-induced mutagenicity at lower concentrations. The constituents of B. dracunculifolia responsible for its mutagenic and antimutagenic effects are probably flavonoids and phenylpropanoids, since these compounds can act either as pro-oxidants or as free radical scavengers depending on their concentration.

Genetic analysis of tumorigenesis: XXXII. Localization of constitutionally amplified KRAS sequences to Chinese hamster chromosomes X and Y by in situ hybridization.

Science.gov (United States)

Stenman, G; Anisowicz, A; Sager, R

1988-11-01

The KRAS gene is constitutionally amplified in the Chinese hamster. We have mapped the amplified sequences by in situ hybridization to two major sites on the X and Y chromosomes, Xq4 and Yp2. No autosomal site was detected despite a search under relaxed hybridization conditions. KRAS DNA is amplified about 50-fold compared to a human cell line known to have a diploid number of KRAS sequences, whereas mRNA expression is 5- to 10-fold lower than in normal human cells. While mRNA expression levels do not necessarily parallel gene copy number, the low expression level strongly suggests that the amplified sequences are transcriptionally silent. It is suggested that the amplified sequences arose from the original KRAS gene on chromosome 8 and that the KRAS sequences on the Y chromosome arose by X-Y recombination.

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

International Nuclear Information System (INIS)

Kaina, B.; Lohrer, H.; Karin, M.; Herrlich, P.

1990-01-01

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

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.

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

Science.gov (United States)

Kaina, B; Lohrer, H; Karin, M; Herrlich, P

1990-01-01

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. Images PMID:2320583

Induction of stable protein-deoxyribonucleic acid adducts in Chinese hamster cell chromatin by ultraviolet light

International Nuclear Information System (INIS)

Strniste, G.F.; Rall, S.C.

1976-01-01

Ultraviolet (uv)-light-mediated formation of protein-DNA adducts in Chinese hamster cell chromatin was investigated in an attempt to compare chromatin alterations induced in vitro with those observed in vivo. Three independent methods of analysis indicated stable protein-DNA associations: a membrane filter assay which retained DNA on the filter in the presence of high salt-detergent; a Sepharose 4B column assay in which protein eluted coincident with DNA; and a CsCl density gradient equilibrium assay which showed both protein and DNA banding at densities other than their respective native densities. Treatment of the irradiated chromatin with DNase provided further evidence that protein--DNA and not protein-protein adducts were being observed in the column assay. There is a fluence-dependent response of protein-DNA adduct formation when the chromatin is irradiated at low ionic strength and is linear for protein over the range studied. When the chromatin is exposed to differing conditions of pH, ionic strength, or divalent metal ion concentration, the quantity of adduct formed upon uv irradiation varies. Susceptibility to adduct formation can be partially explained in terms of the condensation state of the chromatin and other factors such as rearrangement, denaturation, and dissociation of the chromatin components. Besides providing information on the biological significance of these types of uv-induced lesions, this technique may be useful as a probe of chromatin structure

Diversity in host clone performance within a Chinese hamster ovary cell line.

Science.gov (United States)

O'Callaghan, Peter M; Berthelot, Maud E; Young, Robert J; Graham, James W A; Racher, Andrew J; Aldana, Dulce

2015-01-01

Much effort has been expended to improve the capabilities of individual Chinese hamster ovary (CHO) host cell lines to synthesize recombinant therapeutic proteins (rPs). However, given the increasing variety in rP molecular types and formats it may be advantageous to employ a toolbox of CHO host cell lines in biomanufacturing. Such a toolbox would contain a panel of hosts with specific capabilities to synthesize certain molecular types at high volumetric concentrations and with the correct product quality (PQ). In this work, we examine a panel of clonally derived host cell lines isolated from CHOK1SV for the ability to manufacture two model proteins, an IgG4 monoclonal antibody (Mab) and an Fc-fusion protein (etanercept). We show that these host cell lines vary in their relative ability to synthesize these proteins in transient and stable pool production format. Furthermore, we examined the PQ attributes of the stable pool-produced Mab and etanercept (by N-glycan ultra performance liquid chromatography (UPLC) and liquid chromatography - tandem mass spectrometry (LC-MS/MS), respectively), and uncovered substantial variation between the host cell lines in Mab N-glycan micro-heterogeneity and etanercept N and O-linked macro-heterogeneity. To further investigate the capabilities of these hosts to act as cell factories, we examined the glycosylation pathway gene expression profiles as well as the levels of endoplasmic reticulum (ER) and mitochondria in the untransfected hosts. We uncovered a moderate correlation between ER mass and the volumetric product concentration in transient and stable pool Mab production. This work demonstrates the utility of leveraging diversity within the CHOK1SV pool to identify new host cell lines with different performance characteristics. © 2015 American Institute of Chemical Engineers.

Influence of interventional chemotherapy combined with traditional Chinese medicine on the immune function of elderly patients with advanced lung cancer

International Nuclear Information System (INIS)

Jiang Tinghui; Wu Shiyan; Chen Yue; Zhang Qingquan; Zhang Weiwei; Shen Xubo; Wang Qianyao

2010-01-01

Objective: To investigate the influence of interventional chemotherapy combined with traditional Chinese medicine on the immune function in elderly patients with advanced lung cancer and to establish a comprehensive therapeutic pattern which is effective and economical with lower side-effects. Methods: A total of 60 aged patients with lung cancer were randomly and equally divided into two groups with 30 patients in each group. Patients in group A were purely treated with traditional Chinese medicine and patients in group B were treated with a combination of interventional chemotherapy and traditional Chinese medicine. And two therapeutic courses (6-8 weeks) were conducted in both groups. The serum T-lymphocyte subsets levels of CD3, CD4, CD8, CD4/CD8, NK cells and CD4 + CD25 + Treg cell levels were estimated with flow cytometry. The results were statistically analyzed. Results: No significant difference in serum levels of T cell subsets and CD4 + CD25 + Treg cell levels existed between the two groups, both before and after the treatment (P > 0.05). However, after the treatment the CD4 + CD25 + Treg cell level in group B was significantly lower than that in group A (P < 0.05). The short-term effective rate and the total clinical benefit rate in group B were 40% and 73.3% respectively, which were much better than those in group A (20% and 63.3% respectively). Conclusion: Interventional chemotherapy combined with traditional Chinese medicine will not damage the immune function of elderly patients with advanced lung cancer, on the contrary, the combination therapy, through effectively reducing the suppressor T cell level,shows excellent short-term effect. It indicates that interventional chemotherapy combined with Chinese medicine is an effective comprehensive therapeutic mode for elderly patients with advanced lung cancer. (authors)

Cell survival after the combined action of manganese (MnCl2) and X-rays in synchronized Chinese hamster cells

International Nuclear Information System (INIS)

Skreb, Y.; Nagy, B.

1984-01-01

The interactions between the effects of manganese chloride and X-rays were studied in synchronized populations of V79 Chinese hamster fibroblasts. The cells were selected by shaking off asynchronous cultures for detachment of mitotic cells which were plated in petri dishes and exposed to various treatments. Irradiation was carried out with a Philips RT-100 X-ray unit. A final concentration of 0.25 mM MnCl 2 was used. The main parameter was the colony forming ability of the surviving cell fraction. When MnCl 2 was administered over 1 h, its toxicity was low regardless of the phase of the cell cycle. Administered separately, 2 Gy irradiation produced only a slight decrease in survival, less marked in the S phase. However, the two agents together induced a synergistic inhibition of the surviving fraction in the S phase when the metal was given immediately after irradiation. If manganese wad administered 3 h after irradiation the two inhibitory effects apparently remained only additive. It seems that MnCl 2 can impair some repair processes starting immediately after irradiation. (orig.)

Effects of inhaled insoluble 239PuO2 on immune responses following lung immunization

International Nuclear Information System (INIS)

Bice, D.E.; Harris, D.L.; Brooks, A.L.; Mewhinney, J.A.

1978-01-01

To determine if inhaled 239 PuO 2 suppresses immunity in lung-associated lymph nodes, Chinese hamsters were exposed to a polydisperse aerosol of 239 PuO 2 produced at 1150 0 C. The mean lung burden of these animals was estimated to be 10 nCi at 8 days after exposure. At 128, 256 and 400 days after exposure, sham exposed controls and experimental animals were immunized by intratracheal instillation of 1 x 10 8 sheep red blood cells (SRBC). Six days later, they were sacrificed and the number of antibody forming cells (AFC) in lung-associated lymph nodes, spleen and cervical lymph nodes was evaluated. Results of these studies indicated that the number of AFC in lung-associated lymph modes was significantly lower in animals exposed to 239 PuO 2 . Only a few AFC were found in spleen and cervical lymph nodes after intratracheal immunization and the number in exposed animals was not significantly different than in the controls. These data indicate that even though the 239 PuO 2 exposure had suppressed immune responses in lung-associated lymph nodes, their filtering capacity was unaffected and antigen did not translocate to the spleen. We conclude that, at the sacrifice intervals evaluated, the immune function of lung-associated lymph nodes was suppressed and that distant lymphoid tissue (e.g., spleen and cervical lymph nodes) did not replace the immune function of the lung-associated lymph nodes

Induction and removal of DNA interstrand cross-links in V-79 Chinese hamster cells measured by hydroxylapatite chromatography after treatments with bifunctional furocoumarins

International Nuclear Information System (INIS)

Dardalhon, M.; Averbeck, D.

1988-01-01

DNA interstrand crosslinks (CL) photoinduced by bifunctional furocoumarins in V-79 Chinese hamster cells were measured by alkaline denaturation and hydroxylapatite chromatography. Treatments with 5-methoxypsoralen (5-MOP), 8-methoxypsoralen (8-MOP) and 4,5',8-trimethylpsoralen (4,5',8-TMP) and 365 nm irradiation (UVA) confer a dose-dependent linear increase in the amount of double-stranded DNA indicating the induction of CL. Determination in alkaline sucrose gradients of the molecular weight of the DNA and estimation of drug-induced strand breakage allowed quantification of the CL induced. 5-MOP was found to be slightly more effective than 8-MOP whereas 4,5',8-TMP was 9 times more effective for the induction of CL. The fate of CL during post-treatment incubation was also followed. Cells in exponential growth phase were found to be efficient in the removal of CL. (Author)

Poly(ADP-ribose) metabolism in X-irradiated Chinese hamster cells: its relation to repair of potentially lethal damage

International Nuclear Information System (INIS)

Ben-Hur, E.; Elkind, M.M.

1984-01-01

Nicotinamide-adenine dinucleotide (NAD + ) is the substrate used by cells in poly(ADP-ribose) synthesis. X-irradiation of log-phase Chinese hamster cells caused a rapid decrease in NAD + levels which was linearly dependent on radiation dose. The activity of ADP-ribosyl transferase (ADPRT) also increased linearly with radiation dose. The decrease of NAD + was slower, and the increase in ADPRT activity was less pronounced, in a radiation sensitive line, V79-AL162/S-10. An inhibitor of ADPRT, m-aminobenzamide, largely prevented the depletion of cellular NAD + and reduced the rate at which ADPRT activity disappeared during post-irradiation incubation. Post-irradiation treatment with hypertonic buffer or with medium containing D 2 O-which inhibit repair of radiation-induced potentially lethal damage-enhanced the depletion of NAD + and prevented the reduction in ADPRT activity following irradiation. The characteristics of the effects of treatment with hypertonic buffer on NAD + metabolism were qualitatively similar to the effects that such treatment has on radiation-induced cell killing. These results suggest that poly(ADP-ribose) synthesis after irradiation plays a role in the repair of potentially lethal damage. (author)

Laser-UV-microirradiation of Chinese hamster cells: the influence of the distribution of photolesions on unscheduled DNA synthesis

International Nuclear Information System (INIS)

Cremer, C.; Jabbur, G.

1981-01-01

Fibroblastoid Chinese hamster cells synchronized by mitotic selection were microirradiated in G1, using a low power laser-UV-microbeam (lambda = 257 nm). The incident energy was either concentrated on a small part of the nucleus (mode 1) or distributed over the whole nucleus (mode 11). Using the same incident UV energy, the local UV fluences were estimated to differ by two orders of magnitude. Following microirradiation the cells were incubated with [ 3 H]-thymidine for 2 h and thereafter processed for autoradiography. Silver grains were concentrated over the microirradiated part after mode 1 and distributed over the whole nucleus after mode 11 irradiation. To quantify the amount of unscheduled DNA synthesis, the number of grains per nucleus was determined. It increased with the total incident energy, but was not or only slightly affected by the mode of microirradiation, if appropriate autoradiographic conditions were used. The findings suggest that within the investigated range of energy densities (2.7-1000 J/m 2 ), the total amount of unscheduled DNA synthesis depends on the total number of pyrimidine dimers but not on their distribution in nuclear DNA. (author)

Chromosome damage in Chinese hamster cells produced by 125I-UdR at the site of its incorporation

International Nuclear Information System (INIS)

Hughes, W.L.; Weinblatt, A.C.; Prensky, W.

1978-01-01

Metaphase chromosomal aberrations were produced by 125 I-labeled iododeoxyuridine ( 125 I-UdR) incorporated into Chinese hamster Don cells at the end of the S-period of the cell cycle. Chromosome damage and the number of autoradiographic silver grains were recorded for whole cells, for chromosome pairs 4 and 5 and for the X and the Y chromosomes. The X and the Y chromosomes, which label late in S, were at least twice as heavily labeled as chromosome pairs 4 and 5 - two readily recognizable autosomes of similar size. The incidence of chromosome damage was at least six times that which would have been expected from equivalent doses of X-rays and the incidence of damage was directly related to the number of silver grains over each chromosome. It is estimated that it takes four to ten disintegrations to produce a visible chromosome aberration. The finding that chromosome damage is localized at the site of the 125 I decay is most readily explained by the high flux of low energy Auger electrons occurring at the site of the decay of the incorporated 125 I atom. (Auth.)

Monoclonal Antibody L1Mab-13 Detected Human PD-L1 in Lung Cancers.

Science.gov (United States)

Yamada, Shinji; Itai, Shunsuke; Nakamura, Takuro; Yanaka, Miyuki; Chang, Yao-Wen; Suzuki, Hiroyoshi; Kaneko, Mika K; Kato, Yukinari

2018-04-01

Programmed cell death ligand-1 (PD-L1) is a type I transmembrane glycoprotein expressed on antigen-presenting cells. It is also expressed in several tumor cells such as melanoma and lung cancer cells. A strong correlation has been reported between human PD-L1 (hPD-L1) expression in tumor cells and negative prognosis in cancer patients. Here, a novel anti-hPD-L1 monoclonal antibody (mAb) L 1 Mab-13 (IgG 1 , kappa) was produced using a cell-based immunization and screening (CBIS) method. We investigated hPD-L1 expression in lung cancer using flow cytometry, Western blot, and immunohistochemical analyses. L 1 Mab-13 specifically reacted hPD-L1 of hPD-L1-overexpressed Chinese hamster ovary (CHO)-K1 cells and endogenous hPD-L1 of KMST-6 (human fibroblast) in flow cytometry and Western blot. Furthermore, L 1 Mab-13 reacted with lung cancer cell lines (EBC-1, Lu65, and Lu99) in flow cytometry and stained lung cancer tissues in a membrane-staining pattern in immunohistochemical analysis. These results indicate that a novel anti-hPD-L1 mAb, L 1 Mab-13, is very useful for detecting hPD-L1 of lung cancers in flow cytometry, Western blot, and immunohistochemical analyses.

Small Animal Models for Human Metapneumovirus: Cotton Rat is More Permissive than Hamster and Mouse

Science.gov (United States)

Zhang, Yu; Niewiesk, Stefan; Li, Jianrong

2014-01-01

Human metapneumovirus (hMPV) is the second most prevalent causative agent of pediatric respiratory infections worldwide. Currently, there are no vaccines or antiviral drugs against this virus. One of the major hurdles in hMPV research is the difficulty to identify a robust small animal model to accurately evaluate the efficacy and safety of vaccines and therapeutics. In this study, we compared the replication and pathogenesis of hMPV in BALB/c mice, Syrian golden hamsters, and cotton rats. It was found that BALB/c mice are not permissive for hMPV infection despite the use of a high dose (6.5 log10 PFU) of virus for intranasal inoculation. In hamsters, hMPV replicated efficiently in nasal turbinates but demonstrated only limited replication in lungs. In cotton rats, hMPV replicated efficiently in both nasal turbinate and lung when intranasally administered with three different doses (4, 5, and 6 log10 PFU) of hMPV. Lungs of cotton rats infected by hMPV developed interstitial pneumonia with mononuclear cells infiltrates and increased lumen exudation. By immunohistochemistry, viral antigens were detected at the luminal surfaces of the bronchial epithelial cells in lungs. Vaccination of cotton rats with hMPV completely protected upper and lower respiratory tract from wildtype challenge. The immunization also elicited elevated serum neutralizing antibody. Collectively, these results demonstrated that cotton rat is a robust small animal model for hMPV infection. PMID:25438015

Gamma radiation inhibits the appearance of induced ornithine decarboxylase activity in Chinese hamster cells

International Nuclear Information System (INIS)

Ben-Hur, E.; Heimer, Y.M.; Riklis, E.

1981-01-01

Ornithine decarboxylase activity of Chinese hamster cells (ODC, EC 4.1.1.17) can be induced in plateau phase by change of medium. Exposure of the cells to gamma radiation before induction reduces the amount of ODC activity induced. The dose-response curve is exponential with a D 0 of 106 krad. Exposure of BUdR-substituted cells is more effective in reducing ODC induction at high doses, with a D 0 of 38 krad. Cells can recover from the reduction incurred by 74 krad if enzyme induction is delayed for 2 hours after exposure. Treatment of the cells with psoralen-plus-light completely inhibits RNA synthesis without affecting protein synthesis (Heimer, Ben-Hur and Riklis 1977, 1978). Using this procedure it is shown that the effect of gamma radiation on inducible ODC activity is due not only to DNA damage but also involves a post-transcriptional effect. This conclusion is supported by employing a heat shock to inhibit protein synthesis prior to gamma-irradiation of log-phase cells. In such cells the increased activity of ODC upon transfer to 37 0 C is due primarily to enzyme synthesis using pre-existing RNA species during the first few hours. A low concentration of actinomycin D, which inhibits rRNA synthesis, applied during the recovery period, prevents the recovery of the cells' capacity for maximal ODC induction. This may indicate that, in order to recover, the cells have to repair damage to the ribosomes as well as to DNA. (author)

Persistence of experimental Rocio virus infection in the golden hamster (Mesocricetus auratus

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Daniele Freitas Henriques

2012-08-01

Full Text Available Rocio virus (ROCV is an encephalitic flavivirus endemic to Brazil. Experimental flavivirus infections have previously demonstrated a persistent infection and, in this study, we investigated the persistence of ROCV infection in golden hamsters (Mesocricetus auratus. The hamsters were infected intraperitoneally with 9.8 LD50/0.02 mL of ROCV and later anaesthetised and sacrificed at various time points over a 120-day period to collect of blood, urine and organ samples. The viral titres were quantified by real-time-polymerase chain reaction (qRT-PCR. The specimens were used to infect Vero cells and ROCV antigens in the cells were detected by immunefluorescence assay. The levels of antibodies were determined by the haemagglutination inhibition technique. A histopathological examination was performed on the tissues by staining with haematoxylin-eosin and detecting viral antigens by immunohistochemistry (IHC. ROCV induced a strong immune response and was pathogenic in hamsters through neuroinvasion. ROCV was recovered from Vero cells exposed to samples from the viscera, brain, blood, serum and urine and was detected by qRT-PCR in the brain, liver and blood for three months after infection. ROCV induced histopathological changes and the expression of viral antigens, which were detected by IHC in the liver, kidney, lung and brain up to four months after infection. These findings show that ROCV is pathogenic to golden hamsters and has the capacity to cause persistent infection in animals after intraperitoneal infection.

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

International Nuclear Information System (INIS)

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

1990-01-01

The authors 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 activity, which catalyzes the oxidation of hexadecanol to hexadecanoic acid, although the intermediate fatty aldehyde was formed normally. A direct measurement of fatty aldehyde dehydrogenase showed that the FAA.1, strain was defective in this component of FAO activity. FAA.1 is a two-stage mutant that was selected from a previously described parent strain, ZR-82, which is defective in ether lipid biosynthesis and peroxisome assembly. Because of combined defects in ether lipid biosynthesis and fatty alcohol oxidation, the ability of the FAA.1 cells to incorporate hexadecanol into complex lipids was greatly impaired, resulting in a 60-fold increase in cellular fatty alcohol levels. As the FAO deficiency in FAA.1 cells appears to be identical to the defect associated with the human genetic disorder Sjoegren-Larsson syndrome, the FAA.1 cell line may be useful in studying this disease

Neurotensin is an antagonist of the human neurotensin NT2 receptor expressed in Chinese hamster ovary cells.

Science.gov (United States)

Vita, N; Oury-Donat, F; Chalon, P; Guillemot, M; Kaghad, M; Bachy, A; Thurneyssen, O; Garcia, S; Poinot-Chazel, C; Casellas, P; Keane, P; Le Fur, G; Maffrand, J P; Soubrie, P; Caput, D; Ferrara, P

1998-11-06

The human levocabastine-sensitive neurotensin NT2 receptor was cloned from a cortex cDNA library and stably expressed in Chinese hamster ovary (CHO) cells in order to study its binding and signalling characteristics. The receptor binds neurotensin as well as several other ligands already described for neurotensin NT1 receptor. It also binds levocabastine, a histamine H1 receptor antagonist that is not recognised by neurotensin NT1 receptor. Neurotensin binding to recombinant neurotensin NT2 receptor expressed in CHO cells does not elicit a biological response as determined by second messenger measurements. Levocabastine, and the peptides neuromedin N and xenin were also ineffective on neurotensin NT2 receptor activation. Experiments with the neurotensin NT1 receptor antagonists SR48692 and SR142948A, resulted in the unanticipated discovery that both molecules are potent agonists on neurotensin NT2 receptor. Both compounds, following binding to neurotensin NT2 receptor, enhance inositol phosphates (IP) formation with a subsequent [Ca2+]i mobilisation; induce arachidonic acid release; and stimulate mitogen-activated protein kinase (MAPK) activity. Interestingly, these activities are antagonised by neurotensin and levocabastine in a concentration-dependent manner. These activities suggest that the human neurotensin NT2 receptor may be of physiological importance and that a natural agonist for the receptor may exist.

Effect of various 3H-thymidine concentrations on the kinetics of chinese hamster cell division

International Nuclear Information System (INIS)

Yuzhakov, V.V.; Lychev, V.A.

1985-01-01

A study of the asynchronous culture of Chinese hamster fibroblasts by autoradiography has shown that the pulse (15 min) incorporation of 3 H-thymidine in nuclear DNA influences the kinetics of labelled cell proliferation. The results obtained suggest that one of the early biological effects of the pulse incorporation of 3 H-thymidine is a delay in the occurrence of the first mitosis. With the concentration of 3 H-thymidine 37 kBq/ml the slowing down of the movement of labelled cells in the cycle is detected by a shift and overlapping of waves of labelled and unlabelled mitotic cells. In an increase of the concentration up to 370-925 kBq/ml the pattern of the curves of labelled mitotic cells is distorted. These distortions are well interpreted by the nature of change of the index of labelled and unlabelled mitotic cells. After an increase in 3 H-thymidine concentration from 37 up to 370-925 kBq/ml the mitotic activity of cells labelled at the end of S-phase decreases from 1 to o0.6-0.1% respectively. With the concentration of 925 kBq/ml for these cells incorporating 3 H-thymidine at the end of S-phase, a delay of the entry into mitosis reaches 6-8 h. Autoradiography data with assessment of granule density suggest that mitotic activity and the period of delay in the occurrence of mitosis depend on the dose of irradiation with intranuclear tritium

Potassium ion influx measurements on cultured Chinese hamster cells exposed to 60-hertz electromagnetic fields

International Nuclear Information System (INIS)

Stevenson, A.P.; Tobey, R.A.

1985-01-01

Potassium ion influx was measured by monitoring 42 KCl uptake by Chinese hamster ovary (CHO) cells grown in suspension culture and exposed in the culture medium to 60-Hz electromagnetic fields up to 2.85 V/m. In the presence of the field CHO cells exhibited two components of uptake, the same as previously observed for those grown under normal conditions; both these components of influx were decreased when compared to sham-exposed cells. Although decreases were consistently observed in exposed cells when plotted as loge of uptake, the differences between the means of the calculated fluxes of exposed and sham-exposed cells were quite small (on the order of 4-7%). When standard deviations were calculated, there was no significant difference between these means; however, when time-paired uptake data were analyzed, the differences were found to be statistically significant. Cells exposed only to the magnetic field exhibited similar small decreases in influx rates when compared to sham-exposed cells, suggesting that the reduction in K+ uptake could be attributed to the magnetic field. Additionally, intracellular K+ levels were measured over a prolonged exposure period (96 h), and no apparent differences in intracellular K+ levels were observed between field-exposed and sham-exposed cultures. These results indicate that high-strength electric fields have a small effect on the rate of transport of potassium ions but no effect on long-term maintenance of intracellular K+

New cell line development for antibody-producing Chinese hamster ovary cells using split green fluorescent protein

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Kim Yeon-Gu

2012-05-01

Full Text Available Abstract Background The establishment of high producer is an important issue in Chinese hamster ovary (CHO cell culture considering increased heterogeneity by the random integration of a transfected foreign gene and the altered position of the integrated gene. Fluorescence-activated cell sorting (FACS-based cell line development is an efficient strategy for the selection of CHO cells in high therapeutic protein production. Results An internal ribosome entry site (IRES was introduced for using two green fluorescence protein (GFP fragments as a reporter to both antibody chains, the heavy chain and the light chain. The cells co-transfected with two GFP fragments showed the emission of green fluorescence by the reconstitution of split GFP. The FACS-sorted pool with GFP expression had a higher specific antibody productivity (qAb than that of the unsorted pool. The qAb was highly correlated with the fluorescence intensity with a high correlation coefficient, evidenced from the analysis of median GFP and qAb in individual selected clones. Conclusions This study proved that the fragment complementation for split GFP could be an efficient indication for antibody production on the basis of high correlation of qAb with reconstitution of GFP. Taken together, we developed an efficient FACS-based screening method for high antibody-producing CHO cells with the benefits of the split GFP system.

Recovery of subchromosomal DNA synthesis in synchronous V-79 Chinese hamster cells after ultraviolet light exposure

International Nuclear Information System (INIS)

Meechan, P.J.; Carpenter, J.G.

1986-01-01

Previous work obtained from Chinese hamster V-79 cells indicated that, immediately following exposure, UV-induced lesions acted as blocks to elongation of nascent strands, but gradually lost that ability over a 10 h period after exposure to 10 J/m 2 . The work reported herein attempted to examine possible cell cycle mediated alterations in the recovery of DNA synthesis. Kinetic incorporation of radiolabeled thymidine studies indicated that there may have been a more rapid recover of DNA synthesis in cells irradiated in G 1 or G 2 vs cells irradiated in S phase. DNA fiber autoradiograms prepared from synchronous cells indicated that after irradiation in any phase of the cell cycle, the length of newly synthesized DNA was equal to control lengths 1 h after exposure to 5.0Jm 2 (or 1 h after entering S phase for cells irradiated in G 1 or G 2 ). This observed recovery was not solely due to an excision process. No cell cycle mediated difference in the number of dimers induced or removed as a function of cell cycle position was observed. These results appear to be consistent with a continuum of effects, with initiation effects dominating the response at low fluences, gapped synthesis at intermediate fluences and elongation inhibition at high fluences. The fluences at which each event dominates may be cell-line specific. (author)

Association of DNA repair gene XRCC1 and lung cancer susceptibility among nonsmoking Chinese women

DEFF Research Database (Denmark)

Yin, J.; Vogel, Ulla Birgitte; Ma, Y.

2009-01-01

predisposition to cancer risk. To address this question in more detail, we conducted a hospital-based case-control study consisting of 55 lung cancer cases and 74 cancer-free controls matched on age and ethnicity among nonsmoking Chinese women. We analyzed five coding single-nucleotide polymorphisms in the XRCC1...

Effects of intratracheal instillation of bleomycin on phospholipid synthesis in hamster lung tissue slices

International Nuclear Information System (INIS)

Giri, S.N.

1987-01-01

Bleomycin, an antineoplastic drug, is known to produce interstitial pulmonary fibrosis (IPF). As a result, it is commonly employed in various species to produce animal models of fibrosis. We have examined the uptake of [ 14 C] acetate by lung slices and its incorporation into lipids in the slices at various times following intratracheal administration of a fibrogenic dose of bleomycin in hamsters. As compared to saline controls, bleomycin had no effect on [ 14 C] acetate uptake at 4 and 7 days but it increased the uptake at 2 and 14 days after treatment. The incorporation of [ 14 C] acetate into total lipid was significantly reduced to 44, 62, 62, and 75% of the control at 2, 4, 7, and 14 days after bleomycin treatment, respectively. The incorporation into lipid as a percentage of the uptake was 12.2 in control animals whereas in bleomycin-treated animals, it was 4.7, 8.0, 7.3, and 6.9 at the corresponding times. Separation of lipids into various fractions revealed that bleomycin treatment specifically inhibited the synthesis of phosphatidylcholine and neutral lipid at all times of the study. The synthesis of all other phospholipids except phosphatidylethanolamine was depressed at 2 days. The latter was, however, depressed at 7 and 14 days after bleomycin treatment. It was concluded from the present study that bleomycin treatment inhibits the synthesis of phospholipid and neutral lipid and this may eventually lead to decreased surfactant production

Development of lesions in Syrian golden hamsters following exposure to radon daughters and uranium ore dust

International Nuclear Information System (INIS)

Cross, F.T.; Palmer, R.F.; Busch, R.H.; Filipy, R.E.; Stuart, B.O.

1981-01-01

The development of lesions in Syrian Golden hamsters was studied following life-span inhalation exposures to radon, radon daughters and uranium ore dust. Clinical measurements revealed that life-span exposures to radon daughters and uranium ore dust, singly or in combination, caused no significant changes in mortality patterns, body weights or hematological parameters compared with controls. Pulmonary and nonpulmonary lesions are presented. Exposure to uranium ore dust provoked inflammatory and proliferative responses in the lungs consisting of macrophage accumulation, alveolar cell hyperplasia, and adenomatous alteration of alveolar epithelium. The adenomatous lesions did not undergo further morphologic change. Exposure to radon and radon daughters was associated with increased occurrence of bronchiolar epithelial hyperplasia and with metaplastic changes of alveolar epithelium. Squamous carcinoma developed in only a few hamsters and only in those animals receiving radon daughter exposures exceeding 8000 WLM. It is concluded that an animal model other than the hamster would be more appropriate for study of the pulmonary carcinogenic potential of uranium ore alone. (author)

Response to high LET radiation 12C (LET, 295 keV/microm) in M5 cells, a radio resistant cell strain derived from Chinese hamster V79 cells.

Science.gov (United States)

Pathak, R; Sarma, A; Sengupta, B; Dey, S K; Khuda-Bukhsh, A R

2007-01-01

To study the effects of 12C-beam of 295 keV/microm (57.24 MeV) on M5 and Chinese hamster V79 cells by using cytogenetic assays like micronuclei (MN) induction, chromosomal aberrations (CA) and apoptosis. Additionally, the relative survival of these two cell lines was tested by the colony forming ability of the cells, with a view to understanding the mechanism of cellular damages that lead to difference in cell survival. Confluent cells were irradiated with 12C-beam at various doses using 15UD Pelletron accelerator. Cell survival was studied by the colony forming ability of cells. MN assay was done by fluorescent staining. Different types of chromosomal aberrations in metaphase cells were scored at 12 h after irradiation. Apoptosis was measured at different post irradiation times as detected by nuclear fragmentation and DNA ladder was prepared after 48 h of incubation. Dose-dependent decrease in surviving fractions was found in both the cell lines. However, the surviving fractions were higher in M5 cells in comparison to V79 cells when exposed to the same radiation doses. On the other hand, induced MN frequencies, CA frequencies and apoptosis percentages were less in M5 cells than V79 cells. Very good correlations between surviving fractions and induced MN frequencies or induced total CA or induced apoptosis percentages were obtained in this study. The cell strain M5 showed relatively more radio-resistance to 12C-beam compared to Chinese hamster V79 cells in this study. As the MN formation, CA and apoptosis induction were less in M5 cells as compared to parental V79 cells, the higher cell survival in the former could possibly be attributed to their better repairing ability leading to higher cell survival.

Hyperthermic radiosensitization of synchronous Chinese hamster cells: relationship between lethality and chromosomal aberrations

International Nuclear Information System (INIS)

Dewey, W.C.; Sapareto, S.A.; Betten, D.A.

1978-01-01

Synchronous Chinese hamster cells in vitro were obtained by mitotic selection. The cells were heated at 45.5 0 C for 4 min in mitosis, 11 min in G 1 , or 7 min in S sphase and then x-irradiated immediately thereafter. Colony survival from heat alone was 0.30 to 0.45, and the frequency of chromosomal aberrations induced by heat was 0.00, 0.14, or 0.97 for heat treatments during M, G 1 , or S, respectively. As shown previously, lethality from hyperthermia alone is due to chromosomal aberrations only when the cells are heated during S phase. The log survival (D 0 /sup approximately/ = 80 rad) and aberration frequency curves for cells irradiated during mitosis were linear, and the only effect of hyperthermia was to shift the curves in accord with the effect from heat alone. Thus, hyperthermia did not radiosensitize the mitotic cells. The cells irradiated in G 1 were more resistant (D 0 /sup approximately/ = 100 rad) than those irradiated in mitosis, and the survival and aberration frequency curves both had shoulders. The primary effect of hyperthermia was to greatly reduce the shoulders of the curves and to increase the slopes by about 23%. The cells irradiated in S were the most resistant (D 0 /sup approximately/ = 140 rad), and the survival and aberration frequency curves both had large shoulders. For both end points of lethality and chromosomal aberrations, heat selectively radiosensitized S-phase cells relative to G 1 cells by removing most of the shoulder and increasing the slope by about 45%. For cells treated in G 1 or S, the increase in radiosensitization following hyperthermia can be accounted for by an increase in the frequency of chromosomal aberrations

Heterogeneity within populations of recombinant Chinese hamster ovary cells expressing human interferon-gamma.

Science.gov (United States)

Coppen, S R; Newsam, R; Bull, A T; Baines, A J

1995-04-20

The Chinese hamster ovary (CHO) cell line has great commercial importance in the production of recombinant human proteins, especially those for therapeutic use. Much attention has been paid to CHO cell population physiology in order to define factors affecting product fidelity and yield. Such studies have revealed that recombinant proteins, including human interferon-gamma (IFN-gamma), can be heterogeneous both in glycosylation and in proteolytic processing. The type of heterogeneity observed depends on the growth physiology of the cell population, although the relationship between them is complex. In this article we report results of a cytological study of the CHO320 line which expresses recombinant human IFN-gamma. When grown in suspension culture, this cell line exhibited three types of heterogeneity: (1) heterogeneity of the production of IFN-gamma within the cell population, (2) heterogeneity of the number of nuclei and mitotic spindles in dividing cells, and (3) heterogeneity of cellular environment. The last of these arises from cell aggregates which form in suspension culture: Some cells are exposed to the culture medium; others are fully enclosed within the mass with little or no direct access to the medium. Thus, live cells producing IFN-gamma are heterogeneous in their environment, with variable access to O(2) and nutrients. Within the aggregates, it appears that live cells proliferate on a dead cell mass. The layer of live cells can be several cells deep. Specific cell-cell attachments are observed between the living cells in these aggregates. Two proteins, known to be required for the formation of certain types of intercellular junctions, spectrin and vinculin, have been localized to the regions of cell-cell contact. The aggregation of the cells appears to be an active process requiring protein synthesis. (c) 1995 John Wiley & Sons, Inc.

Assessing the nutritional status of elderly Chinese lung cancer patients using the Mini-Nutritional Assessment (MNA® tool

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Zhang L

2013-03-01

Full Text Available Lei Zhang,1,* Yanjun Su,1,* Chen Wang,2 Yongsheng Sha,1 Hong Zhu,3 Shumin Xie,4 Sabrina Kwauk,5 Jing Zhang,2 Yunshou Lin,2 Changli Wang1,*1Department of Thoracic Surgery, Key Laboratory of Cancer Prevention and Therapy, Tianjin Lung Cancer Center, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 2Tianjin Medical University, Tianjin, 3Department of Public Health, Tianjin Medical University, Tianjin, 4Xiangya Medical School of Central-South University, Changsha, People's Republic of China; 5School of Public Health, Harvard University, Boston, Cambridge, MA, USA*These authors contributed equally to this workPurpose: This study assessed the nutritional status of elderly Chinese lung cancer inpatients using a revised version of the Mini-Nutritional Assessment (MNA® tool.Patients and methods: The revised version of the MNA tool was used to assess the nutritional status of 180 elderly Chinese lung cancer inpatients prior to their scheduled surgery between June 2010 and July 2011. Patients' demographic data, anthropometric parameters, and biochemical markers were collected and analyzed.Results: Among the 180 inpatients who underwent the MNA, 9% were malnourished (MNA score < 19, 33% were at risk of malnutrition (MNA score 19–23, and 58% were well nourished (MNA score ≥ 24. There was significant correlation between the MNA scores of patients who were malnourished, at risk of malnutrition, and well nourished (P < 0.001, as well as between total MNA score and most MNA questions. The three patient groups with different nutritional statuses differed significantly in their responses to anthropometrics and global, diet, and subjective assessments.Conclusion: Incidence rates of malnutrition prior to surgery are high among elderly Chinese lung cancer inpatients. The revised MNA is a valid and reliable tool that can be used to assess and prevent malnutrition among these inpatients.Keywords: malnutrition, MNA-SF, nutrition, inpatients, diet

The associations between two vital GSTs genetic polymorphisms and lung cancer risk in the Chinese population: evidence from 71 studies.

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Kui Liu

Full Text Available BACKGROUND: The genetic polymorphisms of glutathione S-transferase (GSTs have been suspected to be related to the development of lung cancer while the current results are conflicting, especially in the Chinese population. METHODS: Data on genetic polymorphisms of glutathione S-transferase Mu 1 (GSTM1 from 68 studies, glutathione S-transferase theta 1 (GSTT1 from 17 studies and GSTM1-GSTT1 from 8 studies in the Chinese population were reanalyzed on their association with lung cancer risk. Odds ratios (OR were pooled using forest plots. 9 subgroups were all or partly performed in the subgroup analyses. The Galbraith plot was used to identify the heterogeneous records. Potential publication biases were detected by Begg's and Egger's tests. RESULTS: 71 eligible studies were identified after screening of 1608 articles. The increased association between two vital GSTs genetic polymorphisms and lung cancer risk was detected by random-effects model based on a comparable heterogeneity. Subgroup analysis showed a significant relationship between squamous carcinoma (SC, adenocarcinoma (AC or small cell lung carcinoma (SCLC and GSTM1 null genotype, as well as SC or AC and GSTT1 null genotype. Additionally, smokers with GSTM1 null genotype had a higher lung cancer risk than non-smokers. Our cumulative meta-analysis demonstrated a stable and reliable result of the relationship between GSTM1 null genotype and lung cancer risk. After the possible heterogeneous articles were omitted, the adjusted risk of GSTs and lung cancer susceptibility increased (fixed-effects model: ORGSTM1 = 1.23, 95% CI: 1.19 to 1.27, P<0.001; ORGSTT1 = 1.18, 95% CI: 1.10 to 1.26, P<0.001; ORGSTM1-GSTT1 = 1.33, 95% CI: 1.10 to 1.61, P = 0.004. CONCLUSIONS: An increased risk of lung cancer with GSTM1 and GSTT1 null genotype, especially with dual null genotype, was found in the Chinese population. In addition, special histopathological classification of lung cancers and a

Mutation to ouabain-resistance in Chinese hamster cells: induction by ethyl methanesulphonate and lack of induction by ionising radiation

International Nuclear Information System (INIS)

Thacker, J.; Stephens, M.A.; Stretch, A.

1978-01-01

The spontaneous frequency of mutants resistant to growth inhibition by ouabian (OUAsup(R) mutants) was found to be about 5.10 -5 per viable cell in uncloned cultures of Chinese hamster V79-4 cells. In freshly-isolated clones or cultures started from a few cells this frequency was initially reduced to about 1.10 -6 in 1 mM ouabain. No increase in the frequency of OUAsup(R) mutants was found in cultures treated with γ-rays despite exploration of such variables as radiation dose, ouabain concentration, post-treatment interval before selection, cell density in selective medium, and clonal state of the cells at the time of adding ouabain (in situ vs. respreading method). A similar negative result was found for accelerated helium ions, for which the mutagenic effectiveness per unit dose has been shown to be about 10 times higher than γ-rays for the induction of thioguanine-resistant mutants in these cells. Recent evidence is reviewed in support of the suggestion that ionising radiation is unable to induce OUAsup(R) mutants because of the severity of the genetic damage it causes. (Auth.)

Effects of drugs, x-rays, and heat on Chinese hamster ovary cells

International Nuclear Information System (INIS)

Tomasovic, S.P.

1977-01-01

The mitotic cell selection technique was used to monitor the effects of various drugs, primarily inhibitors of RNA synthesis, on x-ray-induced G2 delay. Addition of actinomycin D (2 μg/ml), caffeine (19--194 μg/ml), theophylline (18--180 μg/ml), or cordycepin (5--30 μg/ml) immediately before or after irradiation greatly reduced G2 delay and shifted the x-ray transition point (X-TP, the point in G2 beyond which cells are unaffected in their progression by x-rays) away from division. The magnitude of this protective effect increased with concentration. Addition of dimethylsulfoxide (10 6 μg/ml) immediately after irradiation reduced G2 delay but had no effect on the X-TP. The addition of 2-mercapto-1(β-4-pyridethyl) benzimidazole (25--75 μg/ml) or lucanthone (5--20 μg/ml) immediately before irradiation resulted in increased G2 delay, and shifted the X-TP closer to division. Studies of the effects of these drugs on incorporation of tritiated uridine or tritiated leucine into acid insoluble material indicated no correlation between reduction of G2 delay and rates of overall RNA or protein synthesis. Synchronous cells, treated continuously with 15 μg/ml of cordycepin starting in the latter part of S phase, proceeded into mitosis about 30 minutes ahead of controls. Howevr, cordycepin did not reduce mitotic delay observed for cells irradiated in S phase. Continuous treatment during G2 of unirradiated synchronous cells with 15 μg/ml of cordycepin had little effect on accelerating cells into mitosis, yet did reduce delay observed for cells irradiated in G2. These results are consistent with hypotheses requiring synthesis during G2 of critical protein molecules essential for mitosis. Heating mammalian cells induces lethality by an undetermined mechanism. Heat treatment of Chinese hamster ovary cells at 45.5 0 C resulted in an increase in nonhistone protein isolated with DNA

Amrubicin therapy improves patients with refractory small-cell lung cancer: A single-arm confirmatory Chinese clinical study

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Mengli Zheng

2016-09-01

Full Text Available Our objective was to evaluate an open-label, multicenter, single-arm study to appraise whether amrubicin therapy improves patients with refractory small-cell lung cancer in Chinese clinical study. Patients (n=95 with refractory small-cell lung cancer received 3 consecutive days amrubicin therapy for 21 days. Overall response rate of response to amrubicin was 39%. Anemia, febrile neutropenia, thrombocytopenia, hyperglycemia, hyponatremia, infection, elevated serum transaminases levels were appeared, but the incidences of adverse events were very few. Our results suggest amrubicin therapy can improve patients with refractory small-cell lung cancer and may be an effective and safe treatment option.

Additive action of ionizing and non-ionizing radiations throughout the Chinese hamster cell-cycle

International Nuclear Information System (INIS)

Han, A.; Elkind, M.M.

1977-01-01

X-rays and γ-rays produce lesions in nuclear DNA which are qualitatively different from those produced by UV-light. Studies have been made of the effects of X-rays and UV light on the survival of synchronous cultures of Chinese hamster V79 cells. There were qualitative differences in the age-response patterns for survival after single doses of the two types of radiation, but combined UV-and X-irradiation produced enhanced lethality at all ages throughout the cell cycle. The minimum survival from the combined irradiation was at the middle of the S period, and the survival curves at this stage of the cell cycle were further investigated. Exposure to UV immediately before graded X-ray doses removed the shoulder on the X-ray survival curve in a progressive manner, while the D 0 value increased only slightly. The results correspond to complete additivity of X-ray damage to UV damage. Exposure to X-rays immediately before graded UV doses indicated that only part of the damage produced by the X-rays could be added to the UV-damage. Even after X-ray doses which reduced survival to levels which surpassed the shoulder of the UV-only survival curve, the shoulder persisted on the combined treatment survival curves. Measurements were made of the time-course of the change in molecular weight of single-stranded DNA after X-irradiation preceded by UV-irradiation. Only a small amount of slowing of repair of X-ray induced lesions was detected after a large UV dose. Possible mechanisms for the interactions between the two types of damage are discussed. (U.K.)

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

International Nuclear Information System (INIS)

Tomita, Masanori; Suzuki, Norio; Matsumoto, Yoshihisa; Hirano, Kazuya; Umeda, Noriko; Sakai, Kazuo

2000-01-01

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)

Effects of hyperthermia and x irradiation on sister chromatid exchange (SCE) frequency in Chinese hamster ovary (CHO) cells

International Nuclear Information System (INIS)

Livingston, G.K.; Dethlefsen, L.A.

1979-01-01

The BrdUrd labeling method was used to evaluate the effects of hyperthermia, x irradiation, and the combined treatment on the incidence of sister chromatid exchange (SCE) in Chinese hamster ovary (CHO) cells. Cells cultured in McCoy's 5A media containing 10 μM 5-bromodeoxyuridine were synchronized after one cell cycle by mitotic shake-off. Early-G 1 cells were heated by submerging culture flasks in a 44 +- 0.05 0 C water bath for periods of 20, 40, and 60 min. By the same method, other cultures were x irradiated at doses of 100, 200, 400, and 600 rad. A third protocol involved combined treatment of 20 min at 44 0 C followed immediately by one of the above radiation doses. A fourth protocol reversed the sequence of the combined treatment applying x irradiation (200 or 400 rad) followed immediately by hyperthermia. The data showed that hyperthermia and x irradiation both elevated the frequency of SCEs significantly whether applied separately or together. The combined treatment (heat: 20 min at 44 0 C plus varying x-radiation doses) produced results suggestive of a synergistic interaction. The sequence of the heat and x irradiation did not appear to have a significant effect on the production of SCE

Phosphatidylserine biosynthesis in cultured Chinese hamster ovary cells. II. Isolation and characterization of phosphatidylserine auxotrophs

International Nuclear Information System (INIS)

Kuge, O.; Nishijima, M.; Akamatsu, Y.

1986-01-01

Chinese hamster ovary (CHO) cell mutants that required exogenously added phosphatidylserine for cell growth were isolated by using the replica technique with polyester cloth, and three such mutants were characterized. Labeling experiments on intact cells with 32 Pi and L-[U- 14 C]serine revealed that a phosphatidylserine auxotroph, designated as PSA-3, was strikingly defective in phosphatidylserine biosynthesis. When cells were grown for 2 days without phosphatidylserine, the phosphatidylserine content of PSA-3 was about one-third of that of the parent. In extracts of the mutant, the enzymatic activity of the base-exchange reaction of phospholipids with serine producing phosphatidylserine was reduced to 33% of that in the parent; in addition, the activities of base-exchange reactions of phospholipids with choline and ethanolamine in the mutant were also reduced to 1 and 45% of those in the parent, respectively. Furthermore, it was demonstrated that the serine-exchange activity in the parent was inhibited approximately 60% when choline was added to the reaction mixture whereas that in the mutant was not significantly affected. From the results presented here, we conclude the following. There are at least two kinds of serine-exchange enzymes in CHO cells; one (serine-exchange enzyme I) can catalyze the base-exchange reactions of phospholipids with serine, choline, and ethanolamine while the other (serine-exchange enzyme II) does not use the choline as a substrate. Serine-exchange enzyme I, in which mutant PSA-3 is defective, plays a major role in phosphatidylserine biosynthesis in CHO cells. Serine-exchange enzyme I is essential for the growth of CHO cells

P53, K-RAS, β-CATENIN, C-KIT and BAK mutations in the lung cancer of Chinese and Japanese patients

International Nuclear Information System (INIS)

Shuo Xing; Nobotoshi Nawa; Kazuhiro Tanabe; Tadashi Hongyo; Li- Ya Li; Jing-Tian Tang; Mitsunori Ohta

2005-01-01

Seventeen Chinese (Beijing) and 24 Japanese (Osaka) lung cancer cases were analyzed for mutations of p53, K-ras, β-catenin, c-kit and bak genes by PCR-SSCP analysis followed by direct sequencing. Significantly higher mutation frequency of p53 gene, one of key genes for radiation sensitivity, was found in Chinese cases (11/17; 64.7 %) than Japanese cases (8/24; 33.3 %) (p< O.O5). Fourteen of the 16 mutations found in the Chinese cases were transitions at exon 4,5 and intron 4. In the Japanese cases, of the total of 11 mutations, 5 were transitions and 5 were transversions and one was deletion. Six β-catenin mutations were found in 6 Chinese cases (35.3 % ) at codon 53 and 58, and 4 were found in 3 Japanese cases (12.5 %). C-kit mutations were detected in 5 Chinese cases (29.4 %), while no mutations were found in Japanese cases (p< O.O5). No K-ras mutation was found in both Chinese and Japanese cases. For the first time, we report on bak mutation in human lung cancer in Chinese (2/17; 11.8% ) and Japanese cases (2/24; 8.3% ). C-kit and bak genes are also definitive factors to radiosensitivity. These data thus suggest that there were apparent differences in frequency and/or mutational types of p53, β-catenin and c-kit? genes between Chinese and Japanese cases. The differences can be attributed to factors such as lifestyles including smoking and racial and/or environmental factors, and also to the prediction of the response to radiotherapy. (author)

Inhibition of serine palmitoyltransferase in vitro and long-chain base biosynthesis in intact Chinese hamster ovary cells by β-Cl-alanine

International Nuclear Information System (INIS)

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

1987-01-01

Serine palmitoyltransferase (SPT) is a pyridoxal-5'-phosphate dependent enzyme that catalyzes the first committed step of long-chain base (LCB) synthesis. Inhibition of SPT activity and de novo biosynthesis of sphinganine and sphingosine was observed in vitro and in intact Chinese hamster ovary cells (CHO). In vitro studies revealed that inhibition was irreversible and concentration- and time-dependent, which are characteristics of suicide inhibition. Incubation of intact CHO cells with 5 mM β-Cl-alanine for 15 min completely inhibited SPT activity and LCB synthesis from [ 14 C]serine. The concentration dependences of inhibition of SPT activity and LCB formation were identical. There was no loss of viability of recovery of SPT activity over the 2 hour time course of these experiments. The synthesis of several other lipids was not affected by the same treatment. These results establish the association between the activity of SPT and the cellular rate of LCB formation and indicate that β-Cl-alanine can be used to study alterations in cellular LCB synthesis

Humanizing recombinant glycoproteins from Chinese hamster ovary cells

DEFF Research Database (Denmark)

Hansen, Anders Holmgaard; Amann, Thomas; Kol, Stefan

With new tools for gene-editing like zinc-fingers, TALENS and CRISPR, it is now feasible totailor-make the N-Glycoforms for therapeutic glycoproteins that have previously been almost impossible. We here demonstrate a case of humanizing a recombinant human glycoprotein that in Wild type (WT) Chinese...

Transmission and Adaptation of Chronic Wasting Disease to Hamsters and Transgenic Mice: Evidence for Strains▿

OpenAIRE

Raymond, Gregory J.; Raymond, Lynne D.; Meade-White, Kimberly D.; Hughson, Andrew G.; Favara, Cynthia; Gardner, Donald; Williams, Elizabeth S.; Miller, Michael W.; Race, Richard E.; Caughey, Byron

2007-01-01

In vitro screening using the cell-free prion protein conversion system indicated that certain rodents may be susceptible to chronic wasting disease (CWD). Therefore, CWD isolates from mule deer, white-tailed deer, and elk were inoculated intracerebrally into various rodent species to assess the rodents' susceptibility and to develop new rodent models of CWD. The species inoculated were Syrian golden, Djungarian, Chinese, Siberian, and Armenian hamsters, transgenic mice expressing the Syrian g...

Comparative toxicity in rats vs hamsters of inhaled radon daughters with and without uranium ore dust

International Nuclear Information System (INIS)

Gaven, J.C.; Palmer, R.F.; McDonald, K.E.; Lund, J.E.; Stuart, B.O.

1977-01-01

Simultaneous exposures of rats and hamsters to inhaled radon daughters, with and without uranium ore dust, were performed daily for five months. Pulmonary pathology developing in 6 to 13 mo after cessation of daily exposures included interstitial fibrosis, emphysema, epithelial hyperplasia, squamous metaplasia, and malignant neoplasia. Rats showed a greater variety and more severe response to these uranium mine inhalation exposures than did hamsters. Inhalation of radon daughters with uranium ore dust displayed the site of greatest damage, including squamous carcinoma, from the nasopharynx to the lungs. Sixty percent of the rats exposed to radon daughters with ore dust developed primary pulmonary carcinomas, providing an appropriate short-term experimental animal model for investigation of respiratory tract carcinogenesis in uranium miners

Evaluating the toxicity of TiO2-based nanoparticles to Chinese hamster ovary cells and Escherichia coli: a complementary experimental and computational approach

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Alicja Mikolajczyk

2017-10-01

Full Text Available Titania-supported palladium, gold and bimetallic nanoparticles (second-generation nanoparticles demonstrate promising photocatalytic properties. However, due to unusual reactivity, second-generation nanoparticles can be hazardous for living organisms. Considering the ever-growing number of new types of nanoparticles that can potentially contaminate the environment, a determination of their toxicity is extremely important. The main aim of presented study was to investigate the cytotoxic effect of surface modified TiO2-based nanoparticles, to model their quantitative nanostructure–toxicity relationships and to reveal the toxicity mechanism. In this context, toxicity tests for surface-modified TiO2-based nanoparticles were performed in vitro, using Gram-negative bacteria Escherichia coli and Chinese hamster ovary (CHO-K1 cells. The obtained cytotoxicity data were analyzed by means of computational methods (quantitative structure–activity relationships, QSAR approach. Based on a combined experimental and computational approach, predictive models were developed, and relationships between cytotoxicity, size, and specific surface area (Brunauer–Emmett–Teller surface, BET of nanoparticles were discussed.

Simultaneous Determination of Mutagenicity and Toxicity of ...

African Journals Online (AJOL)

A demonstration of cytotoxicity is required (measurement of cell number, culture confluency and inhibition of mitotic index) for in vitro cytogenetic assays. The study therefore investigated whether delayed cytotoxicity can be used to simultaneously predict mutagenicity and cytotoxicty. Chinese hamster lung cells were ...

Personalized treatment strategies for non-small-cell lung cancer in Chinese patients: the role of crizotinib

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Niu FY

2015-05-01

Full Text Available Fei-Yu Niu,1,2 Yi-Long Wu2 1Graduate School, Southern Medical University, Guangzhou, People’s Republic of China; 2Guangdong Lung Cancer Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China Abstract: Anaplastic lymphoma kinase (ALK rearrangement is an oncogene targeted with approved drugs second to epidermal growth factor receptor (EGFR in lung cancer. Crizotinib was developed and introduced into clinical practice rapidly and successfully after the discovery of ALK rearrangement in non-small-cell lung cancer. Chinese and other Asian patients treated with crizotinib seem to have lower toxicity and higher efficacy compared with other ethnicities. Crizotinib showed potent antitumor activity and manageable toxicity in mesenchymal–epithelial transition factor (c-Met/ROS1-positive non-small-cell lung cancer patients, but prospective clinical trials are still needed to confirm its efficacy and safety. Crizotinib appears to be effective against tumors originating from various organs that harbor ALK abnormalities. In the near future, we would classify the tumors by their genetic information beyond organs, such as ALKoma, EGFRoma, and RAFoma, and a single compound could be used for many different types of cancer in different organs. The major challenge of the widespread use of crizotinib in clinical practice is establishing convenient diagnostic techniques for the detection of ALK/c-Met/ROS1. In the present study, we reviewed the application of crizotinib in Chinese patients. Keywords: NSCLC, crizotinib, ALK, c-Met, ROS1

Effects of Chinese medicinal herbs on a rat model of chronic Pseudomonas aeruginosa lung infection.

Science.gov (United States)

Song, Z; Johansen, H K; Moser, C; Høiby, N

1996-05-01

The aim of the study was to evaluate the effects of two kinds of Chinese medicinal herbs, Isatis tinctoria L (ITL) and Daphne giraldii Nitsche (DGN), on a rat model of chronic Pseudomonas aeruginosa lung infection mimicking cystic fibrosis (CF). Compared to the control group, both drugs were able to reduce the incidence of lung abscess (p < 0.05) and to decrease the severity of the macroscopic pathology in lungs (p < 0.05). In the great majority of the rats, the herbs altered the inflammatory response in the lungs from an acute type inflammation, dominated by polymorphonuclear leukocytes (PMN), to a chronic type inflammation, dominated by mononuclear leukocytes (MN). DGN also improved the clearance of P. aeruginosa from the lungs (p < 0.03) compared with the control group. There were no significant differences between the control group and the two herbal groups with regard to serum IgG and IgA anti-P. aeruginosa sonicate antibodies. However, the IgM concentration in the ITL group was significantly lower than in the control group (p < 0.03). These results suggest that the two medicinal herbs might be helpful to CF patients with chronic P. aeruginosa lung infection, DGN being the most favorable.

Proliferative and morphological changes in the pulmonary epithelium of the Syrian golden hamster during carcinogenesis initiated by 210Po alpha alpha-radiation

International Nuclear Information System (INIS)

Shami, S.G.; Thibodeau, L.A.; Kennedy, A.R.; Little, J.B.

1982-01-01

The role of cellular proliferation in a two-stage model of carcinogenesis in the hamster lung was investigated. Syrian golden hamsters were treated intratracheally with either one instillation of 0.2 microCi of 210Po (Po-0 group), seven weekly instillations of BP (0-BP group), or 0.2 microCi 210Po followed 15 weeks later by either seven instillations of 0.9% NaCl solution (Po-Sal group) or seven instillations of BP (Po-BP group). All BP instillations were 3 mg each of BP:ferric oxide (1:1, w/w) carrier particles). Serial sacrifices were performed for up to 85 weeks. Two hr before sacrifice, each animal was given i.p. injections of 200 microCi of [3H]thymidine. Glycol methacrylate section autoradiographs (1 micrometer) were prepared. Labeling indices in the alveolar region, labeling of terminal bronchiolar cells, and morphological changes were examined. Equal numbers of Po-Sal and Po-BP animals developed lung tumors. No tumors were found in Po-0 or 0-BP animals. Tumor development was preceded by the appearance of hyperplastic areas of bronchiolar-type cells in the alveolar region and by changes in morphology of bronchiolar cells. Labeling indices in the alveolar region of the treated groups were slightly increased relative to untreated controls. Labeling of terminal bronchiolar cells was highest in the Po-BP and 0-BP groups and was associated with much inflammation. A single 0.9% NaCl solution instillation also increased proliferation of bronchiolar cells. We conclude that 0.9% NaCl solution instillations may potentiate carcinogenesis in the hamster lung by acting as a nonspecific stimulus to proliferation; in addition, we conclude that not all hyperplasia progresses on to form lung tumors in the Po-BP and Po-Sal groups

Establishment and Characterization of a Novel Chinese Human Lung Adenocarcinoma Cell Line CPA-Yang2 in Immunodeficient Mice

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Shunfang YANG

2009-10-01

Full Text Available Background and objective The recurrence, metastasis and multidrug resistance (MDR in lung cancer are the tough problems worldwide. This study was to establish a novel chinese lung adenocarcinoma cell line with high metastasis potential for exploring the mechanism of reccurrence, development and MDR in lung cancer. Methods The cell came from the abdominal dropsy of a fifty-six years old female patient with lung adenocarcinoma and the tumor markers CA125, CYFRA21-1, CEA, NSE were detected to be higher secretion by radioimmunoassay in the abdominal dropsy. Tumorigenicity of immunodeficient mice was confirmed in 8th passage. The cell growth curve was mapped. Analysis of chromosome karyotype was tested. The gene expression was measured by real-time quantitative PCR. Results The tumorigenesis rate started at 8th passage in 3/10 immunodeficient mice via subcutaneously and the fully tumorigenicity was at 11th passage as well as later passages. Under the microscope, the cell showed oval-shap and adherence. The chromosome karyotype analysis of the cells was sub-triploid. Approximately 1×106 and 1.5×106 cancerous cells were injected into left cardiac ventricle and tail vein of immunodeficient mice respectively. The results showed multiorgan metastasis in the mice after three-four weeks, including mandible, scapula, humerus, vertebral column, femur, rib and brain, liver, adrenal gland, pulmonary in the mice after inoculation. The bone metastasis rate was 100% in the tumor bearing mice by bone scintigraphy and pathology. Quantitative real-time PCR was used to examined and compared with SPC-A-1 lung adenocarcinoma, ESM1, VEGF-C, IL-6, IL-8, AR genes were overexpressed. The novel cell was named CPA-Yang2. Conclusion The characteristics of novel strain CPA-Yang2 is a highly metastasis cell line of Chinese lung adenocarcinoma. It has stable traits, highly metastasis ability and maybe is a MDR lung cancerous cell line. Of course, it’s a good experimental

Preventive effect of Chinese traditional medicine-Qing-Xue granula on radiation induced lung injury in mice

International Nuclear Information System (INIS)

Wang Xiaozhen; Ji Wei; Jiang Heng; Zhao Lujun; Yang Weizhi; Yang Yufei; Wang Luhua

2012-01-01

Objective: To evaluate whether oral administration of Chinese traditional medicine, Qing-Xue granula, can prevent mouse lung injury caused by thoracic radiation. Methods: 128 BalB/C mice were divided into 4 groups: control (C) group; radiation (R) group; radiation plus high dose Qing-Xue granula (H) group and radiation plus median dose Qing-Xue granula (M) group. The H and M groups were fed 0.64 g and 0.32 g of Qing-Xue granula dissolved in 0.5 ml saline once daily for two months,which were 4 and 2 times of human dosage, respectively. Whole thorax radiation of 12 Gy was delivered with a single ventral-dorsal field with 6 MV X-ray. Group C and group R received 21 days of 0.5 ml saline feeding. Mice were sacrificed at 1, 2, 4 or 6 months after radiation. Macrophage cell count of lung lavage fluid and hydroxyproline content of left lung were assayed, and the lung fibrosis was scored according to the Ashcroft's criteria. The plasma interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) concentration were assayed with ELISA method. The One-way ANOVA was used to test the significance of any differences between groups at each time point. Results: The macrophage cell number of lung lavage fluid was significantly lower in the 1 st month in group M than in group R (2:4, q =3.92, P 0.05). The hydroxyproline content of group H was significantly lower than group R in the 1 st and 6 th months (q =3.62, 3.54, all P nd , 4 th and 6 th months (q=3.38 -4.16, all P st month (q=3.53, P 0.05). The VEGF concentration was significantly higher in group R than group C since the 2 nd month (q =3.12 - 3.78, P nd and 6 th months (q =3.08 - 3.92, all P<0.05). Conclusions: Oral Chinese traditional medicine, Qing-Xue granula, could prevent radiation induced lung fibrosis in mice, especially at high dosage. The degree of elevation of VEGF in plasma was not parallel with that of lung fibrosis. (authors)

Inhibition of X-ray-induced potentially lethal damage (PLD) repair in aerobic plateau-phase Chinese hamster cells by misonidazole

International Nuclear Information System (INIS)

Brown, D.M.

1984-01-01

The effect of the 2-nitroimidazole radiosensitizer misonidazole (MISO) and the hydrophilic analog SR-2508 on the repair of X-ray-induced potentially lethal damage (PLD) was studied in plateau-phase Chinese Hamster ovary (HA-1) cells. It was found that although MISO does not radiosensitize aerobic cells, it inhibits the repair of PLD. However, under hypoxic conditions, MISO has no effect on PLD repair. The major portion of the inhibition of PLD repair in aerobic cells requires the presence of MISO only during irradiation; little or no additional inhibition occurs when MISO is present during the postirradiation repair period. Also, treatment of aerobic cells with 5 mM MISO for either 5 or 30 min prior to irradiation is equally inhibitory. This suggests that the presence of MISO in some way modifies the initial lesion under aerobic conditions since it does not increase cell killing as determined by immediate plating but inhibits subsequent repair. The inhibition is concentration dependent; 0.5 mM MISO inhibits PLD repair by one-half while 5-10 mM totally inhibits the repair measured 6 hr postirradiation. This phenomenon suggests that radiosensitization of tissue in vivo by MISO and other 2-nitroimidazoles may not be unequivocal proof of the presence of hypoxic cells

Phosphatidylserine biosynthesis in cultured Chinese hamster ovary cells. III. Genetic evidence for utilization of phosphatidylcholine and phosphatidylethanolamine as precursors

International Nuclear Information System (INIS)

Kuge, O.; Nishijima, M.; Akamatsu, Y.

1986-01-01

We reported that Chinese hamster ovary (CHO) cells contain two different serine-exchange enzymes (I and II) which catalyze the base-exchange reaction of phospholipid(s) with serine and that a phosphatidylserine-requiring mutant (strain PSA-3) of CHO cells is defective in serine-exchange enzyme I and lacks the ability to synthesize phosphatidylserine. In this study, we examined precursor phospholipids for phosphatidylserine biosynthesis in CHO cells. When mutant PSA-3 and parent (CHO-K1) cells were cultured with [ 32 P]phosphatidylcholine, phosphatidylserine in the parent accumulated radioactivity while that in the mutant was not labeled significantly. On the contrary, when cultured with [ 32 P]phosphatidylethanolamine, the mutant incorporated the label into phosphatidylserine more efficiently than the parent. Furthermore, we found that mutant PSA-3 grew normally in growth medium supplemented with 30 microM phosphatidylethanolamine as well as phosphatidylserine and that the biosynthesis of phosphatidylserine in the mutant was normal when cells were cultured in the presence of exogenous phosphatidylethanolamine. The simplest interpretation of these findings is that phosphatidylserine in CHO cells is biosynthesized through the following sequential reactions: phosphatidylcholine----phosphatidylserine----phosphatidylethanolamine--- - phosphatidylserine. The three reactions are catalyzed by serine-exchange enzyme I, phosphatidylserine decarboxylase, and serine-exchange enzyme II, respectively

An inhibitor of potentially lethal damage (PLD) repair reduces the frequency of γ-ray mutations in cultured Chinese hamster V79 cells

International Nuclear Information System (INIS)

Yokoiyama, A.; Kada, T.; Kuroda, Y.

1992-01-01

Cordycepin (3'-deoxyadenosine, 3 - dA) is an RNA antimetabolite and a radiosensitizer in cultured mammalian cells. In the present paper, the effects of 3'-dA on γ-ray-induced lethality and 6-thioguanine (6TG)-resistant mutations in cultured Chinese hamster V79 cells were examined. 3'-dA had the effect of sensitizing the lethality induced by γ-rays. The potentially lethal damage (PLD) repair produced by post-incubation cells in Hanks' solution after γ-irradiation was almost completely suppressed by 5x10 -5 M 3'-dA. When cells were irradiated with 10 Gy γ-rays and incubated with 3'-dA for 5 h, the frequency of 6TG-resistant mutations induced by γ-rays decreased to 1/6 of that of the irradiated cells incubated without 3'-dA. The decrease in the frequency of γ-ray-induced mutations was dependent on the length of incubation time with 3'-dA. It is suggested that the inhibition of PLD repair by 3'-dA may be that of error-prone repair. (author). 26 refs.; 5 figs

Defective DNA cross-link removal in Chinese hamster cell mutants hypersensitive to bifunctional alkylating agents

International Nuclear Information System (INIS)

Hoy, C.A.; Thompson, L.H.; Mooney, C.L.; Salazar, E.P.

1985-01-01

DNA repair-deficient mutants from five genetic complementation groups isolated previously from Chinese hamster cells were assayed for survival after exposure to the bifunctional alkylating agents mitomycin C or diepoxybutane. Groups 1, 3, and 5 exhibited 1.6- to 3-fold hypersensitivity compared to the wild-type cells, whereas Groups 2 and 4 exhibited extraordinary hypersensitivity. Mutants from Groups 1 and 2 were exposed to 22 other bifunctional alkylating agents in a rapid assay that compared cytotoxicity of the mutants to the wild-type parental strain, AA8. With all but two of the compounds, the Group 2 mutant (UV4) was 15- to 60-fold more sensitive than AA8 or the Group 1 mutant (UV5). UV4 showed only 6-fold hypersensitivity to quinacrine mustard. Alkaline elution measurements showed that this compound produced few DNA interstrand cross-links but numerous strand breaks. Therefore, the extreme hypersensitivity of mutants from Groups 2 and 4 appeared specific for compounds the main cytotoxic lesions of which were DNA cross-links. Mutant UV5 was only 1- to 4-fold hypersensitive to all the compounds. Although the initial number of cross-links was similar for the three cell lines, the efficiency of removal of cross-links was lowest in UV4 and intermediate in UV5. These results suggest that the different levels of sensitivity are specifically related to different efficiencies of DNA cross-link removal. The phenotype of hypersensitivity to both UV radiation and cross-link damage exhibited by the mutants in Groups 2 and 4 appears to differ from those of the known human DNA repair syndromes

Lung cancer risk associated with Thr495Pro polymorphism of GHR in Chinese population.

Science.gov (United States)

Cao, Guochun; Lu, Hongna; Feng, Jifeng; Shu, Jian; Zheng, Datong; Hou, Yayi

2008-04-01

The incidence of lung cancer has been increasing over recent decades. Previous studies showed that polymorphisms of the genes involved in carcinogen-detoxication, DNA repair and cell cycle control comprise risk factors for lung cancer. Recent observations revealed that the growth hormone receptor (GHR) might play important roles in carcinogenesis and Rudd et al. found that the Thr495Pro polymorphism of GHR was strongly associated with lung cancer risk in Caucasians living in the UK (OR = 12.98, P = 0.0019, 95% CI: 1.77-infinity). To test whether this variant of GHR would modify the risk of lung cancer in Chinese population, we compared the polymorphism between 778 lung cancer patients and 781 healthy control subjects. Our results indicate that the frequency of 495Thr (2.8%) allele in cases was significantly higher than in controls (OR = 2.04, P = 0.006, 95% CI: 1.21-3.42) which indicated this allele might be a risk factor for lung cancer. Further analyses revealed Thr495Pro variant was associated with lung cancer in the subpopulation with higher risk for lung cancer: male subpopulation, still-smokers subpopulation and the subpopulation with familial history of cancer. In different histological types of lung cancer, Thr495Pro SNP was significantly associated with small cell and squamous cell lung cancer, but not with adenocarcinoma, which suggested a potential interaction between this polymorphism and metabolic pathways related to smoking. The potential gene-environment interaction on lung cancer risk was evaluated using MDR software. A significant redundant interaction between Thr495Pro polymorphism and smoking dose and familial history of cancer was identified and the combination of genetic factors and smoking status or familial history of cancer barely increased the cancer risk prediction accuracy. In conclusion, our results suggested that the Thr495Pro polymorphism of GHR was associated with the risk of lung cancer in a redundant interaction with smoking and

DNA replication in ultraviolet light irradiated Chinese hamster cells: the nature of replicon inhibition and post-replication repair

International Nuclear Information System (INIS)

Doniger, J.

1978-01-01

DNA replication in ultraviolet light irradiated Chinese hamster cells was studied using techniques of DNA fiber autoradiography and alkaline sucrose sedimentation. Bidirectionally growing replicons were observed in the autoradiograms independent of the irradiation conditions. After a dose of 5 J/m 2 at 254 nm the rate of fork progression was the same as in unirradiated cells, while the rate of replication was reduced by 50%. After a dose of 10J/m 2 the rate of fork progression was reduced 40%, while the replication rate was only 25% of normal. Therefore, at low doses of ultraviolet light irradiation, the inhibition of DNA replication is due to reduction in the number of functioning replicons, while at higher doses the rate of fork progression is also slowed. Those replicons which no longer function after irradiation are blocked in fork movement rather than replicon initiation. After irradiation, pulse label was first incorporated into short nascent strands, the average size of which was approximately equal to the distance between pyrimidine dimers. Under conditions where post-replication repair occurs these short strands were eventually joined into larger pieces. Finally, the data show that slowing post-replication repair with caffeine does not slow fork movement. The results presented here support the post-replication repair model of 'gapped synthesis' and rule out a major role for 'replicative bypass'. (author)

Analysis of metastasis of melanoma-bearing hamsters in thermal neutron capture therapy

International Nuclear Information System (INIS)

Ueda, Masataka; Mishima, Yutaka; Ichihashi, Masamitsu

1985-01-01

Melanoma-bearing hamsters were divided into three groups: the MG I was treated with both 10 B 1 -para-boronophenylalanine.HCl ( 10 B 1 -BPA) and neutron capture therapy (NCT); the MG II was treated with NCT alone; and the control group (MG III). The most satisfactory effect on regression was seen in the MG I. When the opposite site to the transplanted tumor site was exposed to thermal neutrons, no enhanced effect on metastasis was seen. Tumor cells of MG I and MG II were transplanted subcutaneously 24 hr after NCT into normal hamsters (MG It and MG IIt), and their growth and metastasis abilities were examined. MG It cells possessed neither growth nor metastasis ability; while MG IIt cells showed normal growth and metastasis abilities. Lethal effects on tumor cells seemed to occur in the MG I at 24 hr after NCT, suggesting no effects of NCT on the metastasis ability of tumor cells. Metastasis was seen in 2 of 8 animals in the MG III; however, inhibitory effects on tumor cells were the same as those in the other groups MG I and MG II. When the cells were exposed to 100 rad and 300 rad of gamma rays to assess effects of gamma rays during NCT, neither tumor growth nor lung metastasis was affected. When the tumor was excised with 5 mm margin, relapse occurred in a high incidence. There was no difference in lung metastasis between NCT and gamma irradiation. (Namekawa, K.)

Study of the combined effects of smoking and inhalation of uranium ore dust, radon daughters and diesel oil exhaust fumes in hamsters and dogs. Final report

Energy Technology Data Exchange (ETDEWEB)

Cross, F.T.; Palmer, R.F.; Filipy, R.E.; Busch, R.H.; Stuart, B.O.

1978-09-01

Exposure to particulates from uranium ore dust and diesel exhaust soot provoked inflammatory and proliferative responses in lungs. Also exposure to radon and radon daughters yielded increased occurrences of bronchiolar epithelial hyperplasia and metaplastic changes of alveolar epithelium. The data suggest that this cellular change is also a precursor of premalignant change in hamsters. The authors suggest an animal model other than the hamster based on two observations: (1) the Syrian golden hamster has been shown to be highly refractory to carcinoma induction; and (2) that when exposed to realistic levels of agents in life-span exposure regimens, the hamster does not develop lesions. Dog studies with cigarette smoke exposure showed mitigating effects on radon daughter induced respiratory tract cancer. Two reasons are suggested although no empirical evidence was gathered. A strict comparison of human and animal exposures and interpolative models are not possible at this time. (PCS)

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

International Nuclear Information System (INIS)

Hasegawa, K.; Kuge, O.; Nishijima, M.; Akamatsu, Y.

1989-01-01

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

Effects of ultraviolet irradiation on the rate and sequence of DNA replication in synchronized Chinese hamster cells

International Nuclear Information System (INIS)

Meyn, R.E.; Hewitt, R.R.; Thomson, L.F.; Humphrey, R.M.

1976-01-01

The effects of ultraviolet light (uv) irradiation on the rate of DNA replication in synchronized Chinese hamster ovary (CHO) cells were investigated. A technique for measuring semiconservative DNA replication was employed that involved growing the cells in medium containing 5-bromodeoxyuridine and subsequently determining the amount of DNA that acquired hybrid buoyant density in CsCl density gradients. One of the advantages of this technique was that it allowed a characterization of the extent of DNA replication as well as rate after irradiation. It was found that while there was a dose-dependent reduction in the rate of DNA replication following uv-irradiation, doses of up to 10 J/m 2 (which produce many dimers per replicon) did not prevent the ultimate replication of the entire genome. Hence, we conclude that dimers cannot be absolute blocks to DNA replication. In order to account for the total genome replication observed, a mechanism must exist that allows genome replication between dimers. The degree of reduction in the rate of replication by uv was the same whether the cells were irradiated at the Gl-S boundary or 1 h into S-phase. Previous work had shown that cells in early S-phase are considerably more sensitive to uv than cells at the G1-S boundary. Experiments specifically designed to test for reiterative replication showed that uv does not induce a second round of DNA replication within the same S-phase

Karyotype evolution and phylogenetic relationships of hamsters (Cricetidae, Muroidea, Rodentia) inferred from chromosomal painting and banding comparison.

Science.gov (United States)

Romanenko, Svetlana A; Volobouev, Vitaly T; Perelman, Polina L; Lebedev, Vladimir S; Serdukova, Natalya A; Trifonov, Vladimir A; Biltueva, Larisa S; Nie, Wenhui; O'Brien, Patricia C M; Bulatova, Nina Sh; Ferguson-Smith, Malcolm A; Yang, Fengtang; Graphodatsky, Alexander S

2007-01-01

The evolutionary success of rodents of the superfamily Muroidea makes this taxon the most interesting for evolution studies, including study at the chromosomal level. Chromosome-specific painting probes from the Chinese hamster and the Syrian (golden) hamster were used to delimit homologous chromosomal segments among 15 hamster species from eight genera: Allocricetulus, Calomyscus, Cricetulus, Cricetus, Mesocricetus, Peromyscus, Phodopus and Tscherskia (Cricetidae, Muroidea, Rodentia). Based on results of chromosome painting and G-banding, comparative maps between 20 rodent species have been established. The integrated maps demonstrate a high level of karyotype conservation among species in the Cricetus group (Cricetus, Cricetulus, Allocricetulus) with Tscherskia as its sister group. Species within the genera Mesocricetus and Phodopus also show a high degree of chromosomal conservation. Our results substantiate many of the conclusions suggested by other data and strengthen the topology of the Muroidea phylogenetic tree through the inclusion of genome-wide chromosome rearrangements. The derivation of the muroids karyotypes from the putative ancestral state involved centric fusions, fissions, addition of heterochromatic arms and a great number of inversions. Our results provide further insights into the karyotype relationships of all species investigated.

Species comparison of liver cancers induced by internally deposited /sup 144/Ce or /sup 239/Pu in dogs and Chinese hamsters

International Nuclear Information System (INIS)

Muggenburg, B.A.; Brooks, A.L.; Hahn, F.F.; Boecker, B.B.; McClellan, R.O.

1984-01-01

The risk of liver cancer from alpha-emitting radionuclides has been estimated for people from studies of patients injected with Thorotrast, which contains an alpha-emitting radionuclide. There is no corresponding estimation of the risk of liver cancers in people from internally-deposited beta-emitting radionuclides because of the lack of human data. Life-span studies in Beagle dogs exposed by inhalation to /sup 144/CeCl/sub 3/, a beta-emitting radionuclide, or by injection to /sup 239/Pu citrate, an alpha-emitting radionuclide, and in Chinese hamsters exposed by intravenous injections to /sup 144/Ce-/sup 144/Pr citrate or /sup 239/Pu citrate have provided information on liver cancers in these species. These radionuclides accumulated in the liver resulting in significant radiation exposure of the liver. Liver cancer occurred long after exposure. When the lifetime risks of liver cancer were calculated, /sup 239/Pu was found to be more effective than /sup 144/Ce in inducing liver cancers by factor of 10 to 12. The risk of liver cancer from internally-deposited beta emitters for people are estimated by assuming this relationship for people

Effect of neon ions on synchronized Chinese hamster cells

International Nuclear Information System (INIS)

Raju, M.R.; Carpenter, S.G.; Tokita, N.; Howard, J.

1985-01-01

The variation in radiosensitivity across the cell cycle after exposure to neon ions and 60 Co γ-rays is reported for cultured hamster cells. The cells were first synchronized by mitotic selection, then resynchronized in the region of the G 1 /S boundary by treatment with 10 -3 M hydroxyurea. Although the use of hydroxyurea improves the synchrony, it does sensitize cells at the G 1 /S boundary to some degree. The cells were exposed at the plateau and the distal peak position of a neon ion beam modified by a 10 cm wide ridge filter. The results indicate that the variation (ratio of maximum to minimum survival after fixed doses of radiation that are approximately matched to produce similar cell killing) was approximately 80 to 100-fold for 60 Co γ-rays and neon ions at the plateau, and 25-fold for distal peak neon ions. While the r.b.e. of distal peak neon ions decreased rapidly with increasing dose for cells in late S-phase, the r.b.e. is independent of dose for cells at the G 1 /S boundary. (author)

Effect of neon ions on synchronized Chinese hamster cells

Energy Technology Data Exchange (ETDEWEB)

Raju, M.R.; Carpenter, S.G.; Tokita, N. (Los Alamos National Lab., NM (USA)); Howard, J. (Lawrence Berkeley Lab., CA (USA))

1985-08-01

The variation in radiosensitivity across the cell cycle after exposure to neon ions and /sup 60/Co ..gamma..-rays is reported for cultured hamster cells. The cells were first synchronized by mitotic selection, then resynchronized in the region of the G/sub 1//S boundary by treatment with 10/sup -3/ M hydroxyurea. Although the use of hydroxyurea improves the synchrony, it does sensitize cells at the G/sub 1//S boundary to some degree. The cells were exposed at the plateau and the distal peak position of a neon ion beam modified by a 10 cm wide ridge filter. The results indicate that the variation (ratio of maximum to minimum survival after fixed doses of radiation that are approximately matched to produce similar cell killing) was approximately 80 to 100-fold for /sup 60/Co ..gamma..-rays and neon ions at the plateau, and 25-fold for distal peak neon ions. While the r.b.e. of distal peak neon ions decreased rapidly with increasing dose for cells in late S-phase, the r.b.e. is independent of dose for cells at the G/sub 1//S boundary.

Diagnostic imaging of lung cancer with In-111-MDEGD

International Nuclear Information System (INIS)

Nakajima, Susumu; Hayashi, Hideo; Maeda, Tomio

1987-01-01

Indium-111-mono DTPA-ethyleneglycol Ga deuterporphyrin (In-111-MDEGD) is a new tumor imaging agent in lung cancer. The agent has been studied with golden hamsters bearing adenocarcinoma, C57 black mice bearing Lewis lung adenocarcinoma, and nude mice bearing human lung adenocarcinoma xerografts. It has been revealed that the tumor-to-lung, tumor-to-kidney, and tumor-to-blood ratios are higher for In-111-MDEGD than for Ga-67 citrate widely used in imaging tumors, and that the agent is not accumulated in inflammatory lesions. The results were encouraging enough to start clinical diagnostic trials in lung cancer. In this paper, an overview of In-111-MDEGD, along with its preliminary data, is given. (Namekawa, K.)

Elimination of radioactivity after intratracheal instillation of tritiated 3, 4-benzopyrene in hamsters

Energy Technology Data Exchange (ETDEWEB)

Pylev, L N; Roe, F J.C.; Warwick, G P

1969-01-01

Injection and recovery experiments of tritiated 3,4-benzopyrene (BaP) injected alone or with particulate carriers into hamsters were performed. After 21 days, asbestos or carbon black carriers had significantly increased the retention of BaP in the lung. Elimination was rapid at first (2 weeks: and little influenced by carrier; slower rate of elimination was noted after that. Carriers increased recoverable macrophages but decreased the amount of radioactivity per macrophage. Radioactivity was similar in all groups for kidney, liver, blood, feces, and urine.

Ectopic expression of human mTOR increases viability, robustness, cell size, proliferation, and antibody production of chinese hamster ovary cells.

Science.gov (United States)

Dreesen, Imke A J; Fussenegger, Martin

2011-04-01

Engineering of mammalian production cell lines to improve titer and quality of biopharmaceuticals is a top priority of the biopharmaceutical manufacturing industry providing protein therapeutics to patients worldwide. While many engineering strategies have been successful in the past decade they were often based on the over-expression of a single transgene and therefore limited to addressing a single bottleneck in the cell's production capacity. We provide evidence that ectopic expression of the global metabolic sensor and processing protein mammalian target of rapamycin (mTOR), simultaneously improves key bioprocess-relevant characteristics of Chinese hamster ovary (CHO) cell-derived production cell lines such as cell growth (increased cell size and protein content), proliferation (increased cell-cycle progression), viability (decreased apoptosis), robustness (decreased sensitivity to sub-optimal growth factor and oxygen supplies) and specific productivity of secreted human glycoproteins. Cultivation of mTOR-transgenic CHO-derived cell lines engineered for secretion of a therapeutic IgG resulted in antibody titers of up to 50 pg/cell/day, which represents a four-fold increase compared to the parental production cell line. mTOR-based engineering of mammalian production cell lines may therefore have a promising future in biopharmaceutical manufacturing of human therapeutic proteins. Copyright © 2010 Wiley Periodicals, Inc.

Analysis of protein incorporation of radioactive isotopes in the Chinese hamster ovary cell cycle by electronic sorting and gel microelectrophoresis

Energy Technology Data Exchange (ETDEWEB)

Pipkin, J.L.; Anson, J.F.; Hinson, W.G.; Schol, H.; Burns, E.R.; Casciano, D.A.

1986-03-01

The patterns of (3H)-leucine and (32P)-phosphate incorporation of proteins extracted with varying molarities of sodium chloride were analyzed from nuclei physically sorted from six fluorescence windows after propidium iodine staining of the G0 + G1 and G2 + M phases of the Chinese hamster ovary (CHO) cell cycle. Eight hundred nanograms of protein were used in each electrophoretic analysis obtained from 200,000 nuclei, a portion of the sample, from each window. Autoradiography was performed in a two-dimensional polyacrylamide gel ultra-microelectrophoresis apparatus (UMEA) designed and fabricated in this laboratory. There was a net reduction and/or loss of (3H)-leucine- and (32P)-phosphate-labeled protein regions from the autoradiographs occurring primarily in the G2 + M phase. Two phosphorylated proteins that were stage specific were observed in partitions of the G2 + M phase. The use of isolated proteins and the coelectrophoresis of these markers demonstrated the similarity in mobility of a number of proteins seen in the autoradiographs of proteins extracted with high and low salt molarities and implied they are synonymous. Coelectrophoresis indicated that a substantial number of high molecular weight proteins that decreased or disappeared at late stages of G2 + M and early mitosis were composed, in part, of nucleolar proteins.

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)

Duffy, J.J.; Carper, S.W.; Gerner, E.W.

1987-01-01

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

Pathogenesis and host response in Syrian hamsters following intranasal infection with Andes virus.

Directory of Open Access Journals (Sweden)

David Safronetz

2011-12-01

Full Text Available Hantavirus pulmonary syndrome (HPS, also referred to as hantavirus cardiopulmonary syndrome (HCPS, is a rare but frequently fatal disease caused by New World hantaviruses. In humans HPS is associated with severe pulmonary edema and cardiogenic shock; however, the pathogenesis of this disease remains unclear largely due to a lack of suitable animal models for the study of disease progression. In this study we monitored clinical, virological, pathophysiological parameters and host immunological responses to decipher pathological factors and events in the lethal Syrian hamster model of HPS following intranasal inoculation of Andes virus. Transcriptional profiling of the host gene responses demonstrated a suppression of innate immune responses in most organs analyzed during the early stage of infection, except for in the lung which had low level activation of several pro-inflammatory genes. During this phase Andes virus established a systemic infection in hamsters, with viral antigen readily detectable in the endothelium of the majority of tissues analyzed by 7-8 days post-inoculation. Despite wide-spread infection, histological analysis confirmed pathological abnormalities were almost exclusively found in the lungs. Immediately preceding clinical signs of disease, intense activation of pro-inflammatory and Th1/Th2 responses were observed in the lungs as well as the heart, but not in peripheral organs, suggesting that localized immune-modulations by infection is paramount to pathogenesis. Throughout the course of infection a strong suppression of regulatory T-cell responses was noted and is hypothesized to be the basis of the aberrant immune activations. The unique and comprehensive monitoring of host immune responses to hantavirus infection increases our understanding of the immuno-pathogenesis of HPS and will facilitate the development of treatment strategies targeting deleterious host immunological responses.

Mutations of the resistance to 6-thioguanine after exposure of Chinese hamster cells at G1 phase to x-radiation and subsequent treatment with cytosine arabinoside combined with hydroxyurea

International Nuclear Information System (INIS)

Elisova, T.V.; Feoktistova, T.P.; Stavrakova, N.M.

1988-01-01

A study was made of the effect of two-hour treatment of Chinese hamster cells with cytosine arabinoside (AraC) combined with hydroxyurea (HU) at the G 1 phase of the cell cycle on lethal and mutagenic effects of X-radiation (50 to 400 cGy). The inhibitors were shown to increase a spontaneous mutation level of the resistance to 6-thioguanine: this increase augmented by 3 times as the time the treatment increased from 1-2 to 6 h. However, while shorply enhancing the inactivating effect of X-radiation (the enhancement coefficient was 2.6) Arac+HU caused an additive, or a somewhat lesser, effect as estimated by the yield of mutations. It is suggested that AraC combined with hydroxyurea fail to modify the radiation-induced premutation damages

Ataxia Telangiectasia-Mutated (ATMPolymorphisms and Risk of Lung Cancer in a Chinese Population

Directory of Open Access Journals (Sweden)

Ajay A. Myneni

2017-06-01

Full Text Available BackgroundThe ataxia telangiectasia-mutated (ATM gene has a key role in DNA repair including activation and stabilization of p53, which implicates the importance of ATM polymorphisms in the development of cancer. This study aims to investigate the association of two ATM single-nucleotide polymorphisms (SNPs with lung cancer, as well as their potential interaction with p53 gene and other known risk factors of lung cancer.MethodsA population-based case–control study was conducted in Taiyuan city, China with 399 cases and 466 controls matched on the distribution of age and sex of cases. The two ATM gene SNPs, ATMrs227060 and ATMrs228589 as well as p53 gene SNP, p53rs1042522 were genotyped using Sequenom platform. Unconditional logistic regression models were used to estimate crude and adjusted odds ratios (aOR and 95% confidence intervals (CIs. Adjusted models controlled for age, sex, and smoking status.ResultsThe study showed that TT genotype of ATMrs227060 (aOR = 1.58, 95% CI: 1.06–2.35 and AA genotype of ATMrs228589 were significantly associated with lung cancer (aOR = 1.50, 95% CI: 1.08–2.08 in a recessive model. Additionally, carrying variant genotypes of ATMrs227060 (TT, ATMrs228589 (AA, and p53rs1042522 (CC concomitantly was associated with much higher risk (aOR = 3.68, 95% CI: 1.43–9.45 of lung cancer than carrying variant genotypes of any one of the above three SNPs. We also found multiplicative and additive interaction between tea drinking and ATMrs227060 in association with lung cancer.ConclusionThis study indicates that ATM gene variants might be associated with development of lung cancer in Chinese population. These results need to be validated in larger and different population samples.

Effect of Bcl-xL overexpression on sialylation of Fc-fusion protein in recombinant Chinese hamster ovary cell cultures.

Science.gov (United States)

Lee, Jong Hyun; Kim, Yeon-Gu; Lee, Gyun Min

2015-01-01

The sialic acid of glycoproteins secreted by recombinant Chinese hamster ovary (rCHO) cells can be impaired by sialidase under culture conditions which promote the extracellular accumulation of this enzyme. To investigate the effect of Bcl-xL overexpression on the sialylation of glycoproteins produced in rCHO cell culture, two rCHO cell lines producing the same Fc-fusion protein, which were derived from DUKX-B11 and DG44, respectively, were engineered to have regulated Bcl-xL overexpression using the Tet-off system. For both cell lines, Bcl-xL overexpression improved cell viability and extended culture longevity in batch cultures. As a result, a maximum Fc-fusion protein titer increased by Bcl-xL overexpression though the extent of titer enhancement differed between the two cell lines. With Bcl-xL overexpression, the sialylation of Fc-fusion protein, which was assessed by isoelectric focusing gel and sialic acid content analyses, decreased more slowly toward the end of batch cultures. This was because Bcl-xL overexpression delayed the extracellular accumulation of sialidase activity by reducing cell lysis during batch cultures. Taken together, Bcl-xL overexpression in rCHO cell culture increased Fc-fusion protein production and also reduced the impairment of sialylation of Fc-fusion protein by maintaining high viability during batch cultures. © 2015 American Institute of Chemical Engineers.

[Histologic study on impeding leukoplakia carcinogenesis of golden hamster cheek pouch about Erigeron breviscapus (Vant) Hand-Mazz].

Science.gov (United States)

Zhou, C T; Zhong, W J; Hua, L; Hu, H F; Jin, Z G

2000-06-01

To observe the effect of Erigeron breviscapus (Vant) Hand Mazz (HEr) in impeding oral leukoplakia carcinogenesis, and to seek effective Chinese herb medicine that can impede precarcinoma of oral mucosas. 132 golden hamsters were randomly divided into model group (60 animals), HEr group (60 animals), and control group 12 animals. Salley's leukoplakia carcinogenesis model of golden hamster cheek pouch was used in this study. HEr was injected into the stomach to impede evolution of carcinogenesis. Pathological specimens were observed via naked eye and light microscope between model group and HEr group. Results were compared. Observation via naked-eye showed that leukoplakia rate of HEr group (18.2%) was lower than that of model group (27.3%). Observation via light microscope showed that carcinogenesis rate descended one fold and displasia rate descended 0.4 fold in HEr group. HEr has exact effect in impeding leukoplakia carcinogenesis.

Neocarzinostatin-mediated DNA damage and repair in wild-type and repair-deficient Chinese hamster ovary cells

International Nuclear Information System (INIS)

Kuo, W.L.; Meyn, R.E.; Haidle, C.W.

1984-01-01

The formation and repair of neocarzinostatin (NCS)-mediated DNA damage were examined in two strains of Chinese hamster ovary cells. The response in strain EM9, a mutant line selected for its sensitivity to ethyl methanesulfonate and shown to have a defect in the repair of X-ray-induced DNA breaks, was compared with that observed in the parental strain (AA8). The DNA strand breaks and their subsequent rejoining were measured using the method of elution of DNA from filters under either alkaline (for single-strand breaks), or nondenaturing conditions (for double-strand breaks). Colony survival assays showed that the mutant was more sensitive to the action of NCS than was the parental strain by a factor of approximately 1.5. Elution analyses showed that the DNA from both strains was damaged by NCS; the mutant displayed more damage than the parent under the same treatment conditions. Single-strand breaks were produced with a frequency of about 10 to 15 times the frequency of double-strand breaks. Both strains were able to rejoin both single-strand breaks and double-strand breaks induced by NCS treatment. The strand break data suggest that the difference in NCS-mediated cytotoxicity between EM9 and AA8 cells may be directly related to the enhanced production of DNA strand breaks in EM9. However, the fact that much higher doses of NCS were required in the DNA studies compared to the colony survival assays implies that either a small number of DNA breaks occur in a critical region of the genome, or that lesions other than DNA strand breaks are partly responsible for the observed cytotoxicity

Chinese hamster ovary cell mitosis and its response to ionizing radiation: A morphological analysis of the living cell

International Nuclear Information System (INIS)

Carlson, J.G.

1989-01-01

Repeated microscopic observations of exponentially growing Chinese hamster ovary cells were made and the times and mitotic stages were recorded in control and irradiated cultures at 37 degree C. As determined by autoradiography, the time from the end of S phase to early prophase (the G2 phase) was 46 min, to breakdown of the nuclear envelope was 91 min, and to restoration of the nuclear envelope was 116 min. The time spent in morphologically distinguishable phases of mitosis and the effects of 0.5, 1.0, 1.5, 2.0, and 4.0 Gy of gamma or X radiation on cells at each phase were determined. Affected cells were found to be delayed without or with reversion to an earlier mitotic stage before recovering and advancing through mitosis. Cells were timed in the five steps comprising delay with reversion: inertia, cessation I, regression, cessation II, and reprogression. No cells treated in late prophase, i.e., within 8-10 min of nuclear envelope breakdown, were delayed by the doses used; therefore the critical or transition point must be situated in middle prophase. Cells irradiated in this stage were not delayed by 0.5 or 1.0 Gy, but suffered a dose-dependent delay with or without reversion after 1.5, 2.0, and 4.0 Gy. Cells irradiated in early prophase and very late interphase responded similarly, but a greater percentage of the latter reverted

Chromosomal aberrations of the Chinese hamster cell line V79 after irradiation with X-rays and heavy ions

International Nuclear Information System (INIS)

Mueller, W.

1985-02-01

The study on hand examines chromosomal aberrations in Chinese hamster 79 cells. Irradiation involved a number of heavy ions ranging from neon to uranium with an energy variation between 0.3 and 20 MeV/u. Linear energy transfer ranged from 270 to 16,300 keV/μm. X-ray tests were run for reasons of comparison. Experiments showed the following results: 1) Aberration rate increases in dependence of nuclear charge number or LET resp. 2) The distribution of the chromosome-damage instances found differed markedly from corresponding measurements following irradiation with thinly ionizing radiation. In contrast to x-irradiation, it is possible, therefore, to obtain high aberration yields in preparations made immediately after irradiation. 3) The maximum of aberration yield after heavy-ion irradiation could be shown to occur as early as 4h after irradiation. This is true in x-irradiation for but small doses. 4) The radiation-sensitizing effect of caffeine and its action on the repair system of the cell could be confirmed for x-irradiation and could be described for heavy ions for the first time. 5) The radiation-protection effect of cysteamine could be re-affirmed for thinly ionizing radiation, however, it could not be verified for heavy ions. 6) Irradiation of cells by means of particles of a defined range supports the hypothesis that the particularly radiation-sensitive regions of the nucleus membrane constitute the cell's crucial target. (orig./MG) [de

A mechanistic study on the effect of dexamethasone in moderating cell death in Chinese Hamster Ovary cell cultures.

Science.gov (United States)

Jing, Ying; Qian, Yueming; Ghandi, Mahmoud; He, Aiqing; Borys, Michael C; Pan, Shih-Hsie; Li, Zheng Jian

2012-01-01

Dexamethasone (DEX) was previously shown (Jing et al., Biotechnol Bioeng. 2010;107:488-496) to play a dual role in increasing sialylation of recombinant glycoproteins produced by Chinese Hamster Ovary (CHO) cells. DEX addition increased sialic acid levels of a recombinant fusion protein through increased expression of α2,3-sialyltransferase and β1,4-galactosyltransferase, but also decreased the sialidase-mediated, extracellular degradation of sialic acid through slowing cell death at the end of the culture period. This study examines the underlying mechanism for this cytoprotective action by studying the transcriptional response of the CHO cell genome upon DEX treatment using DNA microarrays and gene ontology term analysis. Many of those genes showing a significant transcriptional response were associated with the regulation of programmed cell death. The gene with the highest change in expression level, as validated by Quantitative PCR assays with TaqMan® probes and confirmed by Western Blot analysis, was the antiapoptotic gene Tsc22d3, also referred to as GILZ (glucocorticoid-induced leucine zipper). The pathway by which DEX suppressed cell death towards the end of the culture period was also confirmed by showing involvement of glucocorticoid receptors and GILZ through studies using the glucocorticoid antagonist mifepristone (RU-486). These findings advance the understanding of the mechanism by which DEX suppresses cell death in CHO cells and provide a rationale for the application of glucocorticoids in CHO cell culture processes. Copyright © 2011 American Institute of Chemical Engineers (AIChE).

Production and purification of polyclonal anti-hamster ...

African Journals Online (AJOL)

. ... IgG showed high titer and high specificity in the designed ELISA. Purified antibody and its conjugation with HRP are used in research and diagnosis of hamster disease. Key words: Production, purification, hamster immunoglobulins.

Sequence variations in DNA repair gene XPC is associated with lung cancer risk in a Chinese population: a case-control study

International Nuclear Information System (INIS)

Bai, Yun; Ma, Hongxia; Wang, Ying; Liu, Hongliang; Chen, Weihong; Yang, Lin; Jing, Guangfu; Huo, Xiang; Chen, Feng; Liu, Yanhong; Jin, Li; Xu, Liang; Wei, Qingyi; Huang, Wei; Shen, Hongbing; Lu, Daru; Wu, Tangchun; Yang, Xiaobo; Hu, Zhibin; Yuan, Jing; Wang, Feng; Shao, Minhua; Yuan, Wentao; Qian, Ji

2007-01-01

The nucleotide excision repair (NER) protein, xeroderma pigmentosum C (XPC), participates in recognizing DNA lesions and initiating DNA repair in response to DNA damage. Because mutations in XPC cause a high risk of cancer in XP patients, we hypothesized that inherited sequence variations in XPC may alter DNA repair and thus susceptibility to cancer. In this hospital-based case-control study, we investigated five XPC tagging, common single nucleotide polymorphisms (tagging SNPs) in 1,010 patients with newly diagnosed lung cancer and 1,011 matched cancer free controls in a Chinese population. In individual tagging SNP analysis, we found that rs3731055AG+AA variant genotypes were associated with a significantly decreased risk of lung adenocarcinoma [adjusted odds ratio (OR), 0.71; 95% confidence interval (CI), 0.56–0.90] but an increased risk of small cell carcinomas [adjusted OR, 1.79; 95% CI, 1.05–3.07]. Furthermore, we found that haplotype ACCCA was associated with a decreased risk of lung adenocarcinoma [OR, 0.78; 95% CI, 0.62–0.97] but an increased risk of small cell carcinomas [OR, 1.68; 95% CI, 1.04–2.71], which reflected the presence of rs3731055A allele in this haplotype. Further stratified analysis revealed that the protective effect of rs3731055AG+AA on risk of lung adenocarcinoma was more evident among young subjects (age ≤ 60) and never smokers. These results suggest that inherited sequence variations in XPC may modulate risk of lung cancer, especially lung adenocarcinoma, in Chinese populations. However, these findings need to be verified in larger confirmatory studies with more comprehensively selected tagging SNPs

Comparative ecotoxicity of potential biofuels to water flea (Daphnia magna), zebrafish (Danio rerio) and Chinese hamster (Cricetulus griseus) V79 cells.

Science.gov (United States)

Heger, Sebastian; Du, Miaomiao; Bauer, Kevin; Schäffer, Andreas; Hollert, Henner

2018-08-01

The ecotoxicity of two biofuel candidates (1‑octanol and 2‑butanone) was investigated by an integrative test strategy using three bioassays: the acute immobilisation test with water flea (D. magna), the fish embryo acute toxicity test with zebrafish (Danio rerio) and the in vitro micronucleus assay with Chinese hamster (Cricetulus griseus) V79 cells. The median effective concentration (EC 50 ) values were 14.9±0.66mgL -1 for 1‑octanol, and 2152.1±44.6mgL -1 for 2‑butanone in the D. magna test. Both 1‑octanol and 2‑butanone caused teratogenic and lethal effects on zebrafish embryos, while exposure to 1‑octanol significantly induced these effects at concentrations ≥2.0mgL -1 . These results indicate that 1‑octanol exert much higher ecotoxicity than 2‑butanone to D. magna and zebrafish embryos. Moreover, both 1‑octanol and 2‑butanone did not cause significant genotoxic effects, while their metabolites significantly induced micronuclei in V79 cells. The present study proposed an integrative test approach to evaluate the potential ecotoxicity of biofuels using simple, quick and inexpensive bioassays. Copyright © 2018 Elsevier B.V. All rights reserved.

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

2016-01-05

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 (culture media. In a fed-batch process of manufacturing scale bioreactors, two distinguished trends for changes in amino acid concentrations were identified in response to feeding. Ten essential 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. Copyright © 2015 Elsevier B.V. All rights reserved.

Detection of a deuterium isotope effect in di- and trisubstituted alkylphenylnitrosoureas. An SCE study in Chinese hamster V79-E cells

International Nuclear Information System (INIS)

Thust, R.; Mendel, J.; Bach, B.; Schwarz, H.

1985-01-01

The genotoxicity of 1-methyl-3-phenyl-1-nitrosourea (MPNU), 1-methyl-3-(p-chlorophenyl)-1-nitrosourea (C1-MPNU), 1-ethyl-3-phenyl-1-nitrosourea (EPNU), 1,3-dimethyl-3-phenyl-1-nitrosourea (DMPNU) and their derivatives substituted by deuterium in different positions was studied using sister chromatid exchange (SCE) induction in Chinese hamster V79-E cells. Deuterium substitution in the 1-methyl group of MPNU (MPNU-d3) and C1-MPNU (C1-MPNU-d3) diminished the SCE-inducing capacity by 20-30% and by 30-40% in DMPNU (DMPNU-d3B). There was no altered SCE activity detected when the phenyl group of MPNU (MPNU-d5) or the 3-methyl group of DMPNU (DMPNU-d3A) was deuterium labeled. No isotope effect was detected in deuterated EPNU derivatives, presumably due to the instability of these compounds. It is surmised that the easier delocalization of the positive charge in the deuterated alkyl diazonium ion causes a diminished reactivity and therefore influences the type and amount of DNA alkylation. Furthermore, the experiments with DMPNU and its derivatives revealed that, in contrast to mono- and disubstituted nitrosoureas, the biological activities of these very stable trisubstituted nitrosoureas are strongly influenced by a serum factor in the culture fluid

Detection of a deuterium isotope effect in di- and trisubstituted alkylphenylnitrosoureas. An SCE study in Chinese hamster V79-E cells.

Science.gov (United States)

Thust, R; Mendel, J; Bach, B; Schwarz, H

1985-06-01

The genotoxicity of 1-methyl-3-phenyl-1-nitrosourea (MPNU), 1-methyl-3-(p-chlorophenyl)-1-nitrosourea (C1-MPNU), 1-ethyl-3-phenyl-1-nitrosourea (EPNU), 1,3-dimethyl-3-phenyl-1-nitrosourea (DMPNU) and their derivatives substituted by deuterium in different positions was studied using sister chromatid exchange (SCE) induction in Chinese hamster V79-E cells. Deuterium substitution in the 1-methyl group of MPNU (MPNU-d3) and C1-MPNU (C1-MPNU-d3) diminished the SCE-inducing capacity by 20-30% and by 30-40% in DMPNU (DMPNU-d3B). There was no altered SCE activity detected when the phenyl group of MPNU (MPNU-d5) or the 3-methyl group of DMPNU (DMPNU-d3A) was deuterium labeled. No isotope effect was detected in deuterated EPNU derivatives, presumably due to the instability of these compounds. It is surmised that the easier delocalization of the positive charge in the deuterated alkyl diazonium ion causes a diminished reactivity and therefore influences the type and amount of DNA alkylation. Furthermore, the experiments with DMPNU and its derivatives revealed that, in contrast to mono- and disubstituted nitrosoureas, the biological activities of these very stable trisubstituted nitrosoureas are strongly influenced by a serum factor in the culture fluid.

Mucin 5B promoter polymorphism is associated with susceptibility to interstitial lung diseases in Chinese males.

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Chunli Wang

Full Text Available The variation of G>T in the MUC5B promoter (rs35705950 has been associated with idiopathic pulmonary fibrosis (IPF and familial interstitial pneumonia (FIP in Caucasians, but no information is available regarding this variant in the Chinese population. We recruited 405 patients with interstitial lung diseases (ILD, including 165 IPF patients and 2043 healthy controls, for genotyping the MUC5B gene in the Chinese population. One hundred three patients with pneumonia and 360 patients with autoimmune diseases (ADs were recruited as disease controls. Our results indicated that the prevalence of the minor allele (T of the polymorphism rs35705950 in healthy Chinese subjects was approximately 0.66%, which was lower than that described in the Caucasian population. The frequencies of the T allele were 3.33% and 2.22% in IPF and ILD patients, respectively, and these values were significantly higher than those of healthy controls (P = 0.001, OR = 4.332 for IPF, and P = 0.002, OR = 2.855 for ILD. A stratified analysis showed that this variant in MUC5B associated with the risk for ILD mainly in older male Chinese subjects. No difference was observed between patients with pneumonia, AD patients, and healthy controls.

A prospective cohort study among new Chinese coal miners: the early pattern of lung function change

Energy Technology Data Exchange (ETDEWEB)

Wang, M.L.; Wu, Z.E.; Du, Q.G.; Petsonk, E.L.; Peng, K.L.; Li, Y.D.; Li, S.K.; Han, G.H.; Atffield, M.D. [NIOSH, Morgantown, WV (United States)

2005-11-01

The early pattern of lung function changes in 317 newly hired Chinese underground coal miners was compared to 132 referents. This three year prospective cohort study involved a pre-employment and 15 follow up health surveys, including a questionnaire and spirometry tests. Twice a month, total and respirable dust area sampling was done. The authors used a two stage analysis and a linear mixed effects model approach to analyse the longitudinal spirometry data, and to investigate the changes in forced expiratory volume in 1 second (FEV1) over time, controlling for age, height, pack years of smoking, mean respirable dust concentration, the room temperature during testing, and the group x time interaction terms. Results: FEV1 change over time in new miners is non-linear. New miners experience initial rapid FEV1 declines, primarily during the first year of mining, little change during the second year, and partial recovery during the third year. Both linear and quadratic time trends in FEV1 change are highly significant. Smoking miners lost more FEV1 than non-smokers. Referents, all age less than 20 years, showed continued lung growth, whereas the miners who were under age 20 exhibited a decline in FEV1. Conclusion: Dust and smoking affect lung function in young, newly hired Chinese coal miners. FEV1 change over the first three years of employment is non-linear. The findings have implications for both methods and interpretation of medical screening in coal mining and other dusty work: during the first several years of employment more frequent testing may be desirable, and caution is required in interpreting early FEV1 declines.

X-ray induction of 6-thioguanine-resistant mutants in division arrested, G0/G1 phase Chinese hamster ovary cells

Energy Technology Data Exchange (ETDEWEB)

O' Neill, J.P.; Flint, K.B.

The cytotoxic and mutagenic effect of X-irradiation was determined with Chinese hamster ovary cells arrested in the G0/G1 phase of the cell cycle through 9 days incubation in serum-free medium. In comparison with exponential phase cultures, the arrested cells showed increased cytotoxicity and mutation induction over the dose range of 50-800 rad. Exponential cultures showed a linear mutant frequency-survival relationship while the arrested cells showed a biphasic linear relationship. A post irradiation holding period 24 h does not result in any change in the mutant frequency. The increased sensitivity of the arrested cells to the mutagenic effects of X-rays appears to be a cell-cycle phase phenomenon. Upon readdition of serum, the arrested cells re-enter the cell cycle in a synchronous manner, reaching S phase at 10-12 h. Cells irradiated at 5 h after serum addition, i.e. in G1, show a similar dose response for mutant frequency, while those irradiated at 10 h or later, i.e. in late G1, S or G2, show lower mutation induction. These observations are consistent with a chromosome interchange mechanism of mutation induction by X-rays, possibly through interactions between repairing regions of the DNA. Irradiation of cells in the G0/G1 phase allow more time for such interactions in the absence of semiconservative DNA replication. (orig.).

DNA base sequence changes induced by ultraviolet light mutagenesis of a gene on a chromosome in Chinese hamster ovary cells

Energy Technology Data Exchange (ETDEWEB)

Romac, S; Leong, P; Sockett, H; Hutchinson, F [Yale Univ., New Haven, CT (USA). Dept. of Molecular Biophysics and Biochemistry

1989-09-20

The DNA base sequence changes induced by mutagenesis with ultraviolet light have been determined in a gene on a chromosome of cultured Chinese hamster ovary (CHO) cells. The gene was the Excherichia coli gpt gene, of which a single copy was stably incorporated and expressed in the CHO cell genome. The cells were irradiated with ultraviolet light and gpt{sup -} colonies were selected by resistance to 6-thioguanine. The gpt gene was amplified from chromosomal DNA by use of the polymerase chain reaction (PCR) and the amplified DNA sequenced directly by the dideoxy method. Of the 58 sequenced mutants of independent origin 53 were base change mutations. Forty-one base substitutions were single base changes, ten had two adjacent (or tandem) base changes, and one had two base changes separated by a single base-pair. Only one mutant had a multiple base change mutation with two or more well separated base changes. In contrast much higher levels of such mutations were reported in ultraviolet mutagenesis of genes on a shuttle vector in primate cells. Two deletions of a single base-pair were observed and three deletions ranging from 6 to 37 base-pairs. The mutation spectrum in the gpt gene had similarities to the ultraviolet mutation spectra for several genes in prokaryotes, which suggests similarities in mutational mechanisms in prokaryotes and eukaryotes. (author).

Dynamics of neuroepithelial body (NEB) formation in developing hamster lung: Light microscopic autoradiography after 3H-thymidine labeling in vivo

International Nuclear Information System (INIS)

Hoyt, R.F. Jr.; McNelly, N.A.; Sorokin, S.P.

1990-01-01

Autoradiographs were prepared from lungs of a newborn Syrian golden hamster exposed continuously to 3H-thymidine for the final 4.5 days of a normal 16 day gestation. Silver grains were counted over nuclei of 1,298 small-granule endocrine cells in 165 neuroepithelial bodies (NEBs) in the right upper lobe and along the left axial bronchus, where nodal NEBs occurred at branch points and internodal NEBs in the airway between them. Nuclei of 1,005 nonendocrine airway epithelial cells were counted next to the NEBs. Label was distributed differently in the two populations: All nonendocrine cells were labeled, whereas many endocrine cells were not. In NEBs of the right upper lobe, total label (net grains/nuclear profile) averaged only 23% of that in nonendocrine cells. Along the left axial bronchus, mean label in nonendocrine cells and internodal NEBs rose 10-fold between the hilum and the periphery. Increases for both populations were linear and parallel, but total label in the NEBs was consistently lower than that in the surrounding epithelium by 15 grains/nuclear profile. Nodal NEBs were more lightly labeled than those of the internodes, consistent with their earlier formation. A few very heavily labeled small-granule cells (0.9%) occurred singly in the periphery of large, otherwise lightly labeled NEBs. In contrast to NEBs, neurons in 10 bronchial ganglia of the right lung were virtually unlabeled. These arise from vagal neural crest and seem to comprise an entirely distinct population. We conclude that NEBs belong intrinsically to pulmonary endoderm, not neural crest. During fetal life each develops from a cell or cells programmed to stop dividing well ahead of other elements in the epithelium. Their formation is linked closely to early proliferation of the bronchial tree and is an integral part of growth and differentiation of the airway lining

Survival and mutation in clones derived from V79 Chinese hamster cells irradiated with multiple small exposures to far-UV and mid-UV

International Nuclear Information System (INIS)

Ikebuchi, M.; Osmak, M.; Hill, C.

1987-01-01

Clones were isolated from U81 and N80 cells that were established by irradiation of Chinese hamster V79-M12G cells on a once a day schedule with 81 and 80 fractions of 6 J m/sup -2/ far-UV and 150 Jm/sup -2/ mid-UV (UV-B), respectively. These clones were examined for UV sensitivity to cell lethality and induction of mutations at 6TG/sup r/ (resistance to 6-thioguanine) and Oua/sup R/ (resistance to ouabain) loci. Survival curves for these clones indicate that their UV sensitivities to lethality vary from that of M12G cells to that of U81 and N80 parental cells. Clones also show heterogeneity for mutability to mid-UV: For induction of 6TG/sup r/, for example, non-mutable (U814), hypomutable (U815) and hypermutable (U811) were isolated from U81 cells. The authors are investigating by chromosome analysis and repair experiments why resistance to far-UV and mid-UV cell killing in these cells appears to be induced but the resulting survivors have a heterogeneous response to mutation induction by further doses of UV light

Cloning of a Recombinant Plasmid Encoding Thiol-Specific Antioxidant Antigen (TSA) Gene of Leishmania majorand Expression in the Chinese Hamster Ovary Cell Line.

Science.gov (United States)

Fatemeh, Ghaffarifar; Fatemeh, Tabatabaie; Zohreh, Sharifi; Abdolhosein, Dalimiasl; Mohammad Zahir, Hassan; Mehdi, Mahdavi

2012-01-01

TSA (thiol-specific antioxidant antigen) is the immune-dominant antigen of Leishmania major and is considered to be the most promising candidate molecule for a recombinant or DNA vaccine against leishmaniasis. The aim of the present work was to express a plasmid containing the TSA gene in eukaryotic cells. Genomic DNA was extracted, and the TSA gene was amplified by polymerase chain reaction (PCR). The PCR product was cloned into the pTZ57R/T vector, followed by subcloning into the eukaryotic expression vector pcDNA3 (EcoRI and HindIII sites). The recombinant plasmid was characterised by restriction digest and PCR. Eukaryotic Chinese hamster ovary cells were transfected with the plasmid containing the TSA gene. Expression of the L. major TSA gene was confirmed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and Western blotting. The plasmid containing the TSA gene was successfully expressed, as demonstrated by a band of 22.1 kDa on Western blots. The plasmid containing the TSA gene can be expressed in a eukaryotic cell line. Thus, the recombinant plasmid may potentially be used as a DNA vaccine in animal models.

Targeted knock-in of an scFv-Fc antibody gene into the hprt locus of Chinese hamster ovary cells using CRISPR/Cas9 and CRIS-PITCh systems.

Science.gov (United States)

Kawabe, Yoshinori; Komatsu, Shinya; Komatsu, Shodai; Murakami, Mai; Ito, Akira; Sakuma, Tetsushi; Nakamura, Takahiro; Yamamoto, Takashi; Kamihira, Masamichi

2018-05-01

Chinese hamster ovary (CHO) cells have been used as host cells for the production of pharmaceutical proteins. For the high and stable production of target proteins, the transgene should be integrated into a suitable genomic locus of host cells. Here, we generated knock-in CHO cells, in which transgene cassettes without a vector backbone sequence were integrated into the hprt locus of the CHO genome using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 and CRISPR-mediated precise integration into target chromosome (CRIS-PITCh) systems. We investigated the efficiency of targeted knock-in of transgenes using these systems. As a practical example, we generated knock-in CHO cells producing an scFv-Fc antibody using the CRIS-PITCh system mediated by microhomology sequences for targeting. We found that the CRIS-PITCh system can facilitate targeted knock-in for CHO cell engineering. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Inhibition of replicon initiation and DNA elongation in Chinese hamster ovary cells by treatment at 45.5 degrees C

International Nuclear Information System (INIS)

Wong, R.S.; Dewey, W.C.

1982-01-01

Heat treatment of Chinese hamster ovary cells at 45.5 degrees C for 15 minutes resulted in the inhibition of both the replicon initiation and the DNA elongation processes. Analysis of the DNA made after treatment showed that for up to 30 minutes after hyperthermia, there was a significant increase (45-80% above control level) in the amount of labeled DNA less than or equal to 40S in size and having a distinct peak of 20S. Therefore, elongation of 20S molecules into larger molecules was inhibited or slowed down. These small molecules did not accumulate when recovery times were longer than 30 minutes. The DNA made after 120 and 240 minutes postheat incubation was larger than control size and indicated that, although replicon initiation was still inhibited, elongation between replicons into 120S molecules could take place. However, their subsequent elongation into parental-size molecules was inhibited. The same delay in DNA elongation seen in cells examined immediately after treatment was still observed in cells heated and allowed to recover for 30 minutes. Also, after 30 minutes of recovery, heated cells still had more newly synthesized DNA in the single-stranded fraction than did control cells, which indicates that DNA elongation within a replicon is delayed for at least 30 minutes after heating. Furthermore, at 4 hours after heating, the inhibition of elongation of clusters of replicons into parental molecules prevailed

Improved gene amplification by cell-cycle engineering combined with the Cre-loxP system in Chinese hamster ovary cells.

Science.gov (United States)

Matsuyama, Rima; Tsutsui, Tomomi; Lee, Kyoung Ho; Onitsuka, Masayoshi; Omasa, Takeshi

2015-12-01

The dihydrofolate reductase gene amplification system is widely used in Chinese hamster ovary (CHO) cells for the industrial production of therapeutic proteins. To enhance the efficiency of conventional gene amplification systems, we previously presented a novel method using cell-cycle checkpoint engineering. Here, we constructed high-producing and stable cells by the conditional expression of mutant cell division cycle 25 homolog B (CDC25B) using the Cre-loxP system. A bispecific antibody-producing CHO DG44-derived cell line was transfected with floxed mutant CDC25B. After inducing gene amplification in the presence of 250 nM methotrexate, mutant CDC25B sequence was removed by Cre recombinase protein expression. Overexpression of the floxed mutant CDC25B significantly enhanced the efficiency of transgene amplification and productivity. Moreover, the specific production rate of the isolated clone CHO Cre-1 and Cre-2 were approximately 11-fold and 15-fold higher than that of mock-transfected clone CHO Mock-S. Chromosomal aneuploidy was increased by mutant CDC25B overexpression, but Cre-1 and Cre-2 did not show any changes in chromosome number during long-term cultivation, as is the case with CHO Mock-S. Our results suggest that high-producing and stable cells can be constructed by conditionally controlling a cell-cycle checkpoint integrated in conventional gene amplification systems. Copyright © 2015 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Radioprotective action of WR-1065 on radiation-induced DNA strand breaks in cultured Chinese hamster ovary cells

International Nuclear Information System (INIS)

Murray, D.; VanAnkeren, S.C.; Milas, L.; Meyn, R.E.

1988-01-01

We have examined the radioprotective effect of WR-1065 on cultured Chinese hamster ovary cells. The effects of the drug on the induction and rejoining of gamma-ray-induced DNA single-strand breaks (SSBs) and double-strand breaks (DSBs) were measured using alkaline (pH 12.1) and neutral (pH 7.0) elution, respectively. Molecular protection factors (PFs) calculated from these data allowed us to determine whether the degree of modification of strand breakage accurately predicted the PFs measured using the biological end point of cell survival. The drug did protect against the induction of both SSBs and DSBs, although to an extent that did not appear to fully account for the degree of radioprotection in terms of cell killing measured under identical conditions. It is therefore unlikely that radioprotection by WR-1065 occurs simply as a consequence of a general lowering of all types of gamma-ray-induced DNA lesions, and it is possible that the drug could differentially protect against the induction of subsets of these DNA lesions. The rate of SSB rejoining was retarded following preirradiation treatment of cells with WR-1065, but there was no effect on DSB rejoining. Postirradiation treatment with WR-1065 also appeared to retard SSB rejoining but without an accompanying effect on either DSB rejoining or cell survival; however, this effect was largely reversed by the addition of catalase and was, therefore, probably a result of H 2 O 2 generated by autoxidation of the drug. Based on these observations, it would appear that the molecular actions of aminothiol radioprotective compounds that lead to reduced cell killing are much more complex than previously thought

Effect of vitamin E on cytotoxicity, DNA single strand breaks, chromosomal aberrations, and mutation in Chinese hamster V-79 cells exposed to ultraviolet-B light

International Nuclear Information System (INIS)

Sugiyama, M.; Tsuzuki, K.; Matsumoto, K.; Ogura, R.

1992-01-01

The effect of pretreatment with vitamin E on cytotoxicity, DNA single strand breaks, and chromosomal aberrations as well as on mutation induced by ultraviolet-B light (UV-B) was investigated in Chinese hamster V-79 cells. Cellular pretreatment with non-toxic levels of 25 μM α-tocopherol succinate (vitamin E) for 24h prior to exposure resulted in a 10-fold increase in cellular levels of α-tocopherol. Using a colony-forming assay, this pretreatment decreased the cytotoxicity of UV-B light. However, alkaline elution assays demonstrated that pretreatment with vitamin E did not affect the number of DNA single strand breaks caused by UV-B light. UV-B exposure produced a dose-dependent induction of chromosomal aberrations and mutations at the HGPRT locus, and neither of these actions of UV-B was influenced by pretreatment with the vitamin. These results suggest that vitamin E protects cells from UV-B-induced cytotoxicity, possibly through its ability to scavenge free radicals. The genotoxicity induced by UV-B light may not correlate directly with the cytotoxic action of this wavelength region in sunlight. (author)

Optimization of a pH-shift control strategy for producing monoclonal antibodies in Chinese hamster ovary cell cultures using a pH-dependent dynamic model.

Science.gov (United States)

Hogiri, Tomoharu; Tamashima, Hiroshi; Nishizawa, Akitoshi; Okamoto, Masahiro

2018-02-01

To optimize monoclonal antibody (mAb) production in Chinese hamster ovary cell cultures, culture pH should be temporally controlled with high resolution. In this study, we propose a new pH-dependent dynamic model represented by simultaneous differential equations including a minimum of six system component, depending on pH value. All kinetic parameters in the dynamic model were estimated using an evolutionary numerical optimization (real-coded genetic algorithm) method based on experimental time-course data obtained at different pH values ranging from 6.6 to 7.2. We determined an optimal pH-shift schedule theoretically. We validated this optimal pH-shift schedule experimentally and mAb production increased by approximately 40% with this schedule. Throughout this study, it was suggested that the culture pH-shift optimization strategy using a pH-dependent dynamic model is suitable to optimize any pH-shift schedule for CHO cell lines used in mAb production projects. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

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)

Dulout, F.N.; Natarajan, A.T.

1987-01-01

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)

[Genotyping and evaluation of infection dynamics in a Colombian isolate of Leptospira santarosai in hamster as an experimental model].

Science.gov (United States)

Agudelo-Flórez, Piedad; Durango, Harold; Aranzazu, Diego; Rodas, Juan David; Travi, Bruno

2014-01-01

Is necessary to develop models for the study of leptospirosis. To genotype a Colombian strain of Leptospira isolated from a human with Weil´s syndrome and to evaluate its infection dynamics in the hamster experimental model. Genotyping was performed by amplification and sequence analysis of the rrs 16S and lipL32 genes. The median lethal dose was determined in intraperitoneally inoculated hamsters. The patterns of clinical chemistry, the duration of leptospiremia, leptospiruria and pathological findings were studied and compared in the same animal model infected with L. interrogans (Fiocruz L1-130). Molecular typing revealed that the isolate corresponded to the pathogenic species L. santarosai, which was recovered from hamsters´ kidneys and lungs and detected by lipL32 PCR from day 3 post-infection in these organs. There was a marked increase of C-reactive protein in animals at day 5 post-infection (3.25 mg/dl; normal value: 0.3 mg/dl) with decreases by day 18 (2.60 mg/dl: normal value: 0.8 mg/dl). Biomarkers of urea showed changes consistent with possible renal acute failure (day 5 post-infection: 49.01 mg/dl and day 18 post-infection: 53.71 mg/dl). Histopathological changes included interstitial pneumonia with varying degrees of hemorrhage and interstitial nephritis. The pathogenic species L. santarosai was identified in Colombia. Its pathogenicity as determined by tropism to lung and kidney was comparable to that of L. interrogans Fiocruz L1-130, well known for its virulence and pulmonar tropism. The biological aspects studied here had never before been evaluated in an autochthonous isolate.

Genetic variant in the 3'-untranslated region of VEGFR1 gene influences chronic obstructive pulmonary disease and lung cancer development in Chinese population.

Science.gov (United States)

Wang, Hui; Yang, Lei; Deng, Jieqiong; Wang, Bo; Yang, Xiaorong; Yang, Rongrong; Cheng, Mei; Fang, Wenxiang; Qiu, Fuman; Zhang, Xin; Ji, Weidong; Ran, Pixin; Zhou, Yifeng; Lu, Jiachun

2014-09-01

Lung inflammation and epithelial to mesenchymal transition (EMT) are two pathogenic features for the two contextual diseases: chronic obstructive pulmonary disease (COPD) and lung cancer. VEGFR1 (or FLT1) plays a certain role in promoting tumour growth, inflammation and EMT. To simultaneously test the association between the single nucleotide polymorphisms (SNPs) in VEGFR1 and risk of COPD and lung cancer would reveal genetic mechanisms shared by these two diseases and joint aetiology. We conducted a two-population hospital-based case-control study. Three potential functional SNPs (rs664393, rs7326277 and rs9554314) were genotyped in southern Chinese and validated in eastern Chinese to explore their associations with COPD risk in 1511 COPD patients and 1677 normal lung function controls, and with lung cancer risk in 1559 lung cancer cases and 1679 cancer-free controls. We also detected the function of the promising SNP. Individuals carrying the rs7326277C (CT+CC) variant genotypes of VEGFR1 had a significant decrease in risk of both COPD (OR = 0.78; 95% CI = 0.68-0.90) and lung cancer (OR = 0.79; 95% CI = 0.64-0.98), compared with those carrying the rs7326277TT genotype. Functional assays further showed that the rs7326277C genotypes had lower transcriptional activity and caused decreased VEGFR expression, compared with the rs7326277TT genotype. However, no significant association was observed for the other two SNPs (rs664393 and rs9554314) and either COPD or lung cancer risk. Our data suggested that the rs7326277C variant of VEGFR1 could reduce both COPD and lung cancer risk by lowering VEGFR1 mRNA expression; the SNP might be a common susceptible locus for both COPD and lung cancer. © The Author 2014. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Haplotypes of nine single nucleotide polymorphisms on chromosome 19q13.2-3 associated with susceptibility of lung cancer in a Chinese population

DEFF Research Database (Denmark)

Yin, Jiaoyang; Vogel, Ulla Birgitte; Ma, Yegang

2008-01-01

To evaluate the joint effect of nine single nucleotide polymorphisms for three DNA repair genes in the region of chromosome 19q13.2-3 on susceptibility of lung cancer in a Chinese population, we conducted a hospital-based case-control study consisting of 247 lung cancer cases and 253 cancer......-free controls matched on age, gender and ethnicity. Associations between the haplotypes and susceptibility of lung cancer were tested. The global test of haplotype association revealed a statistically significant difference in the haplotype distribution between cases and controls (global test: chi(2) = 60.45, d...

Induction of lyme arthritis in LSH hamsters

International Nuclear Information System (INIS)

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

1988-01-01

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

Comparison of 6-thioguanine-resistant mutation and sister chromatid exchanges in Chinese hamster V79 cells with forty chemical and physical agents

International Nuclear Information System (INIS)

Nishi, Y.; Hasegawa, M.M.; Taketomi, M.; Ohkawa, Y.; Inui, N.

1984-01-01

The induction of sister chromatid exchanges (SCE) and mutation at the hypoxanthine-guanine phosphoribosyl transferase locus and toxicities of 40 different chemical and physical agents were examined on Chinese hamster V79 cells. These agents included mono-, di-, tri-, and polyfunctional alkylating agents, intercalators, gamma-rays, and UV light irradiation. Mutation was measured as resistance to 6-thioguanine and toxicity as loss of cell-plating efficiency. SCE were examined 29 hr after treatment. With the agents examined, a highly positive correlation existed between SCE-inducing and mutagenic potencies, when expressed as increase in the number per a unit dose over the control values. But the great difference of the ratios of mutagenic potencies versus SCE-inducing potencies among agents was observed, the maximal difference in the ratios being about 200-fold. The agents that showed the higher values of the ratio (agents producing more mutations than SCE) were bleomycin, cobalt-60 gamma-rays, all ethylating agents (N-ethyl-N-nitrosourea, N-ethyl-N'-nitro-N-nitrosoguanidine, ethyl methanesulfonate, and diethylsulfate), N-propyl-N-nitrosourea, N-butyl-N-nitrosourea, isopropyl methanesulfonate, intercalating acridine compounds (2-methoxy-6-chloro-9-[3-(ethyl-2-chloroethyl)aminopropylamino]-acridine X 2HCl and 2-methoxy-6-chloro-9-[3-(chloroethyl)-aminopropylamino]acridine 2HCl) and UV light at 254 nm

Alkylarylnitrosoureas--stability in aqueous solution, partition coefficient, alkylating activity and its relationship to SCE induction in Chinese hamster V 79-E cells.

Science.gov (United States)

Mendel, J; Thust, R; Schwarz, H

1982-01-01

The alkylating activity, chemical stability in aqueous solution (pH 7.0; 37 degrees C), and partition coefficient (octanol/water) of the following compounds were determined: 1-methyl-3-phenyl-1-nitrosourea (MPNU), 1-ethyl-3-phenyl-1-nitrosourea (EPNU), 1-isopropyl-3-phenyl-1-nitrosourea (i-PrPNU), 1-methyl-3-(p-fluorophenyl)-1-nitrosourea (F-MPNU), 1-methyl-3-(p-chlorophenyl)-1-nitrosourea (Cl-MPNU), 1-methyl-3-(p-bromophenyl)-1-nitrosourea (Br-MPNU), 1,3-dimethyl-3-phenyl-1-nitrosourea (DMPNU), and 1-methyl-3-naphthyl-1-nitrosocarbamate (NCA). 1-Methyl-1-nitrosourea (MNU) and 1-ethyl-1-nitrosourea (ENU) were used for the comparison. THe rate of decomposition in aqueous solution is discussed concerning the influences of the substituents at the 1- and 3-N-atom. The mono- and disubstituted N-nitrosoureas showed a coarse correlation between alkylating activity and SCE induction in Chinese hamster V 79-E cells. On the other hand, this correlation is missing in the case of NCA, which is a potent SCE inducer despite relatively low alkylating activity. DMPNU is the strongest SCE inducer, but this compound shows a high stability in aqueous solution and, consequently, we were not able to detect an alkylating activity.

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

Histaminergic regulation of seasonal metabolic rhythms in Siberian hamsters.

Science.gov (United States)

I'anson, Helen; Jethwa, Preeti H; Warner, Amy; Ebling, Francis J P

2011-06-01

We investigated whether histaminergic tone contributes to the seasonal catabolic state in Siberian hamsters by determining the effect of ablation of histaminergic neurons on food intake, metabolic rate and body weight. A ribosomal toxin (saporin) conjugated to orexin-B was infused into the ventral tuberomammillary region of the hypothalamus, since most histaminergic neurons express orexin receptors. This caused not only 75-80% loss of histaminergic neurons in the posterior hypothalamus, but also some loss of other orexin-receptor expressing cells e.g. MCH neurons. In the long-day anabolic state, lesions produced a transient post-surgical decrease in body weight, but the hamsters recovered and maintained constant body weight, whereas weight gradually increased in sham-lesioned hamsters. VO(2) in the dark phase was significantly higher in the lesioned hamsters compared to shams, and locomotor activity also tended to be higher. In a second study in short days, sham-treated hamsters showed the expected seasonal decrease in body weight, but weight remained constant in the lesioned hamsters, as in the long-day study. Lesioned hamsters consumed more during the early dark phase and less during the light phase due to an increase in the frequency of meals during the dark and decreased meal size during the light, and their cumulative food intake in their home cages was greater than in the control hamsters. In summary, ablation of orexin-responsive cells in the posterior hypothalamus blocks the short-day induced decline in body weight by preventing seasonal hypophagia, evidence consistent with the hypothesis that central histaminergic mechanisms contribute to long-term regulation of body weight. Copyright © 2011 Elsevier Inc. All rights reserved.

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)

Prise, K.M.; Davies, S.; Stratford, M.R.L.; Michael, B.D.

1992-01-01

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)

Presence of amastigotes in the central nervous system of hamsters infected with Leishmania sp. Presença de amastigotas em sistema nervoso central de hamster infectado com Leishmania sp.

Directory of Open Access Journals (Sweden)

Elisangela de Oliveira

2011-06-01

Full Text Available Visceral leishmaniasis (VL is a severe chronic disease caused by Leishmania (Leishmania infantum chagasi. Better knowledge on the effects caused by this disease can help develop adequate clinical management and treatment. Parasitological and immunohistochemical studies were performed golden hamsters Mesocricetus auratus infected with bone marrow from individuals with VL in the State of Mato Grosso do Sul, central-west Brazil. The effects of parasitism in the spleen, liver, kidneys, lungs, heart and brain of the animals were examined. Eighteen hamsters were inoculated intraperitoneally, and six healthy animals were used as negative controls. The animals were kept in the animal house and checked for clinical signs. Specimens of each organ were examined for the presence of amastigotes. Immunohistochemical technique was performed in all brain specimens and organs negative on the direct examination of parasites. Direct examination of amastigotes was positive in the spleen and liver of all infected animals; 33.3% showed the parasite in the kidneys and lungs, and 16.7% in the heart. Parasitic forms were seen in 83.3% (15/18 of the brain examined. Immunohistochemistry confirmed the results of the direct examination, except in two specimens of lung tissue and in the brain specimens. Other studies are needed to further clarify the effect of the parasite in the central nervous system.A leishmaniose visceral (LV é uma doença crônica grave, causada pelo parasito Leishmania (Leishmania infantum chagasi. Esclarecer as alterações provocadas pela doença é fundamental para que se adotem condutas clínicas e de tratamento adequadas. Com o objetivo de analisar a infecção experimental em hamsters da linhagem golden, Mesocricetus auratus, infectados com tecido de medula óssea de pacientes com LV no Estado de Mato Grosso do Sul, foram realizados estudos parasitológicos e de imunomarcação. Foi verificada a distribuição do parasitismo no baço, f

Characteristics of Chinese herbal medicine usage and its effect on survival of lung cancer patients in Taiwan.

Science.gov (United States)

Li, Te-Mao; Yu, Yang-Hao; Tsai, Fuu-Jen; Cheng, Chi-Fung; Wu, Yang-Chang; Ho, Tsung-Jung; Liu, Xiang; Tsang, Hsinyi; Lin, Ting-Hsu; Liao, Chiu-Chu; Huang, Shao-Mei; Li, Ju-Pi; Lin, Jung-Chun; Lin, Chih-Chien; Liang, Wen-Miin; Lin, Ying-Ju

2018-03-01

In Taiwan, lung cancer remains one of the deadliest cancers. Survival of lung cancer patients remains low, ranging from 6% to 18%. Studies have shown that Chinese herbal medicine (CHM) can be used to induce cell apoptosis and exhibit anti-inflammatoryanti-inflammatory activities in cancer cells. This study aimed to investigate the frequencies and patterns of CHM treatment for lung cancer patients and the effect of CHM on their survival probability in Taiwan. We identified 6939 lung cancer patients (ICD-9-CM: 162). We allocated 264 CHM users and 528 CHM-non users, matched for age, gender, duration, and regular treatment. Chi-square test, conditional multivariable logistic regression, Kaplan-Meier method, and the log-rank test were used in this study. The CHM group was characterized by a longer follow up time and more cases of hyperlipidemia and liver cirrhosis. This group exhibited a lower mortality hazard ratio (0.48, 95% confidence interval [0.39-0.61], p herbs, respectively. Among them, BM was the core CHM of the major cluster, and Jie-Geng (JG) and Mai-Men-Dong-Tang (MMDT) were important CHMs by CHM network analysis. The use of CHM as an adjunctive therapy may reduce the mortality hazard ratio of lung cancer patients. The investigation of their comprehensive CHM prescription patterns might be useful in future large-scale, randomized clinical investigations of agent effectiveness, safety, and potential interactions with conventional treatments for lung cancer patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Highly Efficient Transfer of Chromosomes to a Broad Range of Target Cells Using Chinese Hamster Ovary Cells Expressing Murine Leukemia Virus-Derived Envelope Proteins.

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Teruhiko Suzuki

Full Text Available Microcell-mediated chromosome transfer (MMCT is an essential step for introducing chromosomes from donor cells to recipient cells. MMCT allows not only for genetic/epigenetic analysis of specific chromosomes, but also for utilization of human and mouse artificial chromosomes (HACs/MACs as gene delivery vectors. Although the scientific demand for genome scale analyses is increasing, the poor transfer efficiency of the current method has hampered the application of chromosome engineering technology. Here, we developed a highly efficient chromosome transfer method, called retro-MMCT, which is based on Chinese hamster ovary cells expressing envelope proteins derived from ecotropic or amphotropic murine leukemia viruses. Using this method, we transferred MACs to NIH3T3 cells with 26.5 times greater efficiency than that obtained using the conventional MMCT method. Retro-MMCT was applicable to a variety of recipient cells, including embryonic stem cells. Moreover, retro-MMCT enabled efficient transfer of MAC to recipient cells derived from humans, monkeys, mice, rats, and rabbits. These results demonstrate the utility of retro-MMCT for the efficient transfer of chromosomes to various types of target cell.

Anthracyclines as radiosensitizers. A Cu(II) complex of a simpler analogue modifies DNA in Chinese Hamster V79 cells under low-dose γ radiation

International Nuclear Information System (INIS)

Saurabh Das; Mandal, P.C.

2014-01-01

Hydroxy-9,10-anthraquinones are structural analogues of anthracycline anticancer drugs showing similarity in physicochemical attributes, electrochemical behavior and biophysical interactions. 1,2-dihydroxy-9,10-anthraquinone (Q) and its complexes with Cu(II)/Ni(II) were studied for γ radiation induced modification of DNA in Chinese Hamster V79 cells. The amount of double stranded DNA remaining was ascertained by fluorometric analysis of DNA unwinding using ethidium bromide. Modification of double stranded DNA increased in the presence of Q and Cu(II)-Q when cells were irradiated (0-4.2 Gray). Ni(II)-Q was not that effective. Changing incubation time before recovery of DNA from cells there was evidence for DNA repair that was least for Cu(II)-Q treated cells. Minimum repair in case of Cu(II)-Q treated cells suggest the compound either assists radiation induced damage of agents responsible for repair or interacts with species like H 2 O 2 that assist in repair. Since a hydroxy-9,10-anthraquinone and its Cu(II) complex show radiosensitizing property, anthracyclines that contain a hydroxy-9,10-anthraquinone as the core moiety could also be tried as radiosensitizers in treating cancer. (author)

Alpha 2-adrenergic receptor stimulation of phospholipase A2 and of adenylate cyclase in transfected Chinese hamster ovary cells is mediated by different mechanisms

International Nuclear Information System (INIS)

Jones, S.B.; Halenda, S.P.; Bylund, D.B.

1991-01-01

The effect of alpha 2-adrenergic receptor activation on adenylate cyclase activity in Chinese hamster ovary cells stably transfected with the alpha 2A-adrenergic receptor gene is biphasic. At lower concentrations of epinephrine forskolin-stimulated cyclic AMP production is inhibited, but at higher concentrations the inhibition is reversed. Both of these effects are blocked by the alpha 2 antagonist yohimbine but not by the alpha 1 antagonist prazosin. Pretreatment with pertussis toxin attenuates inhibition at lower concentrations of epinephrine and greatly potentiates forskolin-stimulated cyclic AMP production at higher concentrations of epinephrine. alpha 2-Adrenergic receptor stimulation also causes arachidonic acid mobilization, presumably via phospholipase A2. This effect is blocked by yohimbine, quinacrine, removal of extracellular Ca2+, and pretreatment with pertussis toxin. Quinacrine and removal of extracellular Ca2+, in contrast, have no effect on the enhanced forskolin-stimulated cyclic AMP production. Thus, it appears that the alpha 2-adrenergic receptor in these cells can simultaneously activate distinct signal transduction systems; inhibition of adenylate cyclase and stimulation of phospholipase A2, both via G1, and potentiation of cyclic AMP production by a different (pertussis toxin-insensitive) mechanism

Alpha 2-adrenergic receptor stimulation of phospholipase A2 and of adenylate cyclase in transfected Chinese hamster ovary cells is mediated by different mechanisms

Energy Technology Data Exchange (ETDEWEB)

Jones, S.B.; Halenda, S.P.; Bylund, D.B. (Univ. of Missouri-Columbia (USA))

1991-02-01

The effect of alpha 2-adrenergic receptor activation on adenylate cyclase activity in Chinese hamster ovary cells stably transfected with the alpha 2A-adrenergic receptor gene is biphasic. At lower concentrations of epinephrine forskolin-stimulated cyclic AMP production is inhibited, but at higher concentrations the inhibition is reversed. Both of these effects are blocked by the alpha 2 antagonist yohimbine but not by the alpha 1 antagonist prazosin. Pretreatment with pertussis toxin attenuates inhibition at lower concentrations of epinephrine and greatly potentiates forskolin-stimulated cyclic AMP production at higher concentrations of epinephrine. alpha 2-Adrenergic receptor stimulation also causes arachidonic acid mobilization, presumably via phospholipase A2. This effect is blocked by yohimbine, quinacrine, removal of extracellular Ca2+, and pretreatment with pertussis toxin. Quinacrine and removal of extracellular Ca2+, in contrast, have no effect on the enhanced forskolin-stimulated cyclic AMP production. Thus, it appears that the alpha 2-adrenergic receptor in these cells can simultaneously activate distinct signal transduction systems; inhibition of adenylate cyclase and stimulation of phospholipase A2, both via G1, and potentiation of cyclic AMP production by a different (pertussis toxin-insensitive) mechanism.

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.

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

International Nuclear Information System (INIS)

Kramer, J.M.

1991-01-01

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

The relationship between XRCC1 and XRCC3 gene polymorphisms and lung cancer risk in northeastern Chinese.

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Shujie Guo

Full Text Available BACKGROUND: The prevalence of lung cancer in China will be the world's highest if allowed to proceed uncurbed. To unravel its genetic underpinnings, we sought to investigate the association of three well-characterized nonsynonymous polymorphisms in XRCC1 (Arg194Trp and Arg399Gln and XRCC3 (Thr241Met genes with lung cancer risk in northeastern Chinese. METHODOLOGY/PRINCIPAL FINDINGS: This study was hospital-based in design, encompassing 684 patients with lung cancer and 604 cancer-free controls. Genotyping was performed using the PCR-LDR (ligase detection reactions method. Data were analyzed by R language and multifactor dimensionality reduction (MDR software. Single-locus analysis identified significance in genotype distributions of polymorphism Arg194Trp (P = 0.002 and Arg399Gln (P = 0.017, and in allele distributions of Thr241Met (P = 0.005. Carriers of 399Gln/Gln genotype conferred a 147% increased risk relative to the non-carriers (odds ratio (OR: 2.47; 95% confidence interval (95% CI: 1.48-4.13; P<0.001. For Thr241Met, significance persisted under allelic (OR = 1.63; 95% CI: 1.14-2.33; P = 0.005, additive (OR = 1.64; 95% CI: 1.16-2.32; P = 0.005 and dominant (OR = 1.67; 95% CI: 1.17-2.38; P = 0.004 models. However, common allele combinations were comparable in frequency between patients and controls. In interaction analysis, the overall best MDR model included Arg399Gln and Thr241Met polymorphisms, with a maximal testing accuracy of 63.18% and a maximal cross-validation consistency of 10 out of 10 (P = 0.0175. CONCLUSIONS: Our study significantly demonstrated an independent and synergistic contribution of XRCC1 Arg399Gln and XRCC3 Thr241Met polymorphisms to lung cancer susceptibility in northeastern Chinese.

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

Energy Technology Data Exchange (ETDEWEB)

Spigoti, Geyza; Bartolini, Paolo; Okazaki, Kayo [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)], e-mail: kokazaki@ipen.br; Tsutsumi, Shiguetoshi [Amazon Food Ltd., Tokyo (Japan)], e-mail: fwip5138@mb.infoweb.ne.jp

2009-07-01

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 {sup 60}Co {gamma}-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 {mu}g/ml), 1 h before irradiation, with 1 Gy of {gamma} 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)

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

International Nuclear Information System (INIS)

Spigoti, Geyza; Bartolini, Paolo; Okazaki, Kayo; Tsutsumi, Shiguetoshi

2009-01-01

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 60 Co 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)

The prevalence and prognostic significance of KRAS mutation subtypes in lung adenocarcinomas from Chinese populations

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Zheng DF

2016-02-01

Full Text Available Difan Zheng,1,2,* Rui Wang,1,2,* Yang Zhang,1,2 Yunjian Pan,1,2 Xinghua Cheng,3 Chao Cheng,1,2 Shanbo Zheng,1,2 Hang Li,1,2 Ranxia Gong,1,2 Yuan Li,2,4 Xuxia Shen,2,4 Yihua Sun,1,2 Haiquan Chen1–3,51Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, 2Department of Oncology, Shanghai Medical College, Fudan University, 3Shanghai Chest Hospital, Shanghai Jiao Tong University, 4Department of Pathology, Fudan University Shanghai Cancer Center, 5Institutes of Biomedical Sciences, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workBackground: We performed this retrospective study to identify the prevalence of KRAS mutation in Chinese populations and make a comprehensive investigation of the clinicopathological features of KRAS mutation in these patients.Patients and methods: Patients from 2007 to 2013 diagnosed with primary lung adenocarcinoma who received a radical resection were examined for KRAS, EGFR, HER2, BRAF mutations, and ALK, RET, and ROS1 fusions. Clinicopathological features, including sex, age, tumor–lymph node–metastasis stage, tumor differentiation, smoking status, histological subtypes, and survival information were analyzed.Result: KRAS mutation was detected in 113 of 1,368 patients. Nine different subtypes of KRAS mutation were identified in codon 12, codon 13, and codon 61. KRAS mutation was more frequently found in male patients and former/current smoker patients. Tumors with KRAS mutation had poorer differentiation. Invasive mucinous adenocarcinoma predominant and solid predominant subtypes were more frequent in KRAS mutant patients. No statistical significance was found in relapse-free survival or overall survival between patients with KRAS mutation and patients with other mutations.Conclusion: In Chinese populations, we identified KRAS mutation in 8.3% (113/1,368 of the patients with lung adenocarcinoma. KRAS mutation defines a molecular subset of

Effect of caffeine on gamma-ray induced G2 arrest in well-synchronized Chinese hamster ovary cells in vitro

International Nuclear Information System (INIS)

Masunaga, Shin-ichiro; Keng, P.C.

1996-01-01

G1-rich cells were separated from exponentially growing asynchronous cultured Chinese hamster ovary (CHO-K1) cells by centrifugal elutriation and a Coulter Counter. The G1-rich cells were incubated in medium that contained hydroxyurea (HU) to kill S phase cells and obtain the purest G1/S boundary cells possible. The HU-treated cells were washed, and were again incubated, in medium without HU, to allow these well-synchronized G1/S boundary cells to progress to S and G2/M phases. At various times after release from G1/S boundary, 4 Gy of gamma-ray and/or caffeine was administered to the cells. Eight hours after the removal of HU, cell-cycle analysis was performed with a flow cytometer. G2 arrest induced by gamma-rays was clearly shown when radiation was given earlier than 6.5 hours after HU removal. G2 arrest induced by radiation given 0.5-6.5 hours after HU removal was reduced by caffeine treatment given 6.0-6.5 hours after HU removal. Caffeine released radiation-induced G2 arrest when the radiation was given before the cultured cells entered G2/M phase and when caffeine was applied to the irradiated cells at the time when G1/S boundary cells not treated by radiation or with caffeine entered G2/M phase. Our method of centrifugal elutriation combined with incubation with HU was useful for isolating pure G1/S boundary cells from in vitro asynchronous cultures. (author)

Nicotinamide starvation and inhibition of poly(ADP-Ribose) synthesis enhance the induced mutation in Chinese hamster V79 cells

International Nuclear Information System (INIS)

Okada, Gensaku; Kaneko, Ichiro; Mitsui, Hideki.

1987-01-01

The effects of nicotinamide (NA) deficiency and added NA and 3-aminobenzamide (3AB) on the cytotoxicity and the induction of mutations in Chinese hamster V79-14 cells were investigated. In NA deficiency the addition of NA (up to 4 mM) and 3AB (up to 7.5 mM) was not cytotoxic. The presence of NA prior to exposure to mitomycin C (MMC) or γ-rays produced a dose-dependent increase in the relative cloning ability of DNA-damaged cells. The lethality of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was significantly potentiated by pre-treatment with 5 mM 3AB, but no potentiation by 3AB was observed for MMC, ultraviolet (UV)-B light, or γ-rays. Among cells pre-cultured in NA-free medium there were increased frequencies of mutations at both the hypoxanthineguanine phosphoribosyltransferase (HGPRT) and the adenine phosphoribosyltransferase (APRT) loci following DNA damage. The enhancing effect by NA deficiency was time-dependent. Incubation with NA prior to DNA damage produced a significant reduction in the frequency of mutations. The addition of 3AB to the nicotinamide adenine dinucleotide (NAD + )-depleted cell cultures before or after the DNA damage also strongly increased the frequency of induced mutations, with increasing concentrations of 3AB up to 5 mM, but the frequency was reduced at higher concentrations. The interaction between NA deficiency and the addition of 3AB appears to act synergistically on mutation induction. A correlation was observed between the potential of inhibiting poly (ADP-ribose) polymerase and the enhancement of mutation frequency. (author)

Effect of caffeine on gamma-ray induced G2 arrest in well-synchronized Chinese hamster ovary cells in vitro

Energy Technology Data Exchange (ETDEWEB)

Masunaga, Shin-ichiro [Kyoto Univ., Kumatori, Osaka (Japan). Research Reactor Inst.; Keng, P.C.

1996-11-01

G1-rich cells were separated from exponentially growing asynchronous cultured Chinese hamster ovary (CHO-K1) cells by centrifugal elutriation and a Coulter Counter. The G1-rich cells were incubated in medium that contained hydroxyurea (HU) to kill S phase cells and obtain the purest G1/S boundary cells possible. The HU-treated cells were washed, and were again incubated, in medium without HU, to allow these well-synchronized G1/S boundary cells to progress to S and G2/M phases. At various times after release from G1/S boundary, 4 Gy of gamma-ray and/or caffeine was administered to the cells. Eight hours after the removal of HU, cell-cycle analysis was performed with a flow cytometer. G2 arrest induced by gamma-rays was clearly shown when radiation was given earlier than 6.5 hours after HU removal. G2 arrest induced by radiation given 0.5-6.5 hours after HU removal was reduced by caffeine treatment given 6.0-6.5 hours after HU removal. Caffeine released radiation-induced G2 arrest when the radiation was given before the cultured cells entered G2/M phase and when caffeine was applied to the irradiated cells at the time when G1/S boundary cells not treated by radiation or with caffeine entered G2/M phase. Our method of centrifugal elutriation combined with incubation with HU was useful for isolating pure G1/S boundary cells from in vitro asynchronous cultures. (author)

Hyperthermic survival of Chinese hamster ovary cells as a function of cellular population density at the time of plating

International Nuclear Information System (INIS)

Highfield, D.P.; Holahan, E.V.; Holahan, P.K.; Dewey, W.C.

1984-01-01

The survival of synchronous G 1 or asynchronous Chinese hamster ovary cells in vitro to heat treatment may depend on the cellular population density at the time of heating and/or as the cells are cultured after heating. The addition of lethally irradiated feeder cells may increase survival at 10 -3 by as much as 10- to 100-fold for a variety of conditions when cells are heated either in suspension culture or as monolayers with or without trypsinization. The protective effect associated with feeder cells appears to be associated with close cell-to-cell proximity. However, when cells are heated without trypsinization about 24 hr or later after plating, when adaptation to monolayer has occurred, the protective effect is reduced; i.e., addition of feeder cells enhances survival much less, for example, about 2- to 3-fold at 10 -2 -10 -3 survival. Also, the survival of a cell to heat is independent of whether the neighboring cell in a microcolony is destined to live or die. Finally, if protective effects associated with cell density do occur and are not controlled, serious artifacts can result as the interaction of heat and radiation is studied; for example, survival curves can be moved upward, and thus changed in shape as the number of cells plated is increased with an increase in the hyperthermic treatment or radiation dose following hyperthermia. Therefore, to understand mechanisms and to obtain information relevant to populations of cells in close proximity, such as those in vivo, these cellular population density effects should be considered and understood

Molecular analysis of peroxisome proliferation in the hamster.

Science.gov (United States)

Choudhury, Agharul I; Sims, Helen M; Horley, Neill J; Roberts, Ruth A; Tomlinson, Simon R; Salter, Andrew M; Bruce, Mary; Shaw, P Nicholas; Kendall, David; Barrett, David A; Bell, David R

2004-05-15

Three novel P450 members of the cytochrome P450 4A family were cloned as partial cDNAs from hamster liver, characterised as novel members of the CYP4A subfamily, and designated CYP4A17, 18, and 19. Hamsters were treated with the peroxisome proliferator-activated receptor alpha (PPARalpha) agonists, methylclofenapate (MCP) or Wy-14,643, and shown to develop hepatomegaly and induction of CYP4A17 RNA, and concomitant induction of lauric acid 12- hydroxylase. This treatment also resulted in hypolipidaemia, which was most pronounced in the VLDL fraction, with up to 50% reduction in VLDL-triglycerides; by contrast, blood cholesterol concentration was unaffected by this treatment. These data show that hamster is highly responsive to induction of CYP4A by peroxisome proliferators. To characterise the molecular basis of peroxisome proliferation, the hamster PPARalpha was cloned and shown to encode a 468-amino-acid protein, which is highly similar to rat and mouse PPARalpha proteins. The level of expression of hamster PPARalpha in liver is intermediate between mouse and guinea pig. These results fail to support the hypothesis that the level of PPARalpha in liver is directly responsible for species differences in peroxisome proliferation.

Social context modulates food hoarding in Syrian hamsters

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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.

Hamster and Murine Models of Severe Destructive Lyme Arthritis

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Munson, Erik; Nardelli, Dean T.; Du Chateau, Brian K.; Callister, Steven M.; Schell, Ronald F.

2012-01-01

Arthritis is a frequent complication of infection in humans with Borrelia burgdorferi. Weeks to months following the onset of Lyme borreliosis, a histopathological reaction characteristic of synovitis including bone, joint, muscle, or tendon pain may occur. A subpopulation of patients may progress to a chronic, debilitating arthritis months to years after infection which has been classified as severe destructive Lyme arthritis. This arthritis involves focal bone erosion and destruction of articular cartilage. Hamsters and mice are animal models that have been utilized to study articular manifestations of Lyme borreliosis. Infection of immunocompetent LSH hamsters or C3H mice results in a transient synovitis. However, severe destructive Lyme arthritis can be induced by infecting irradiated hamsters or mice and immunocompetent Borrelia-vaccinated hamsters, mice, and interferon-gamma- (IFN-γ-) deficient mice with viable B. burgdorferi. The hamster model of severe destructive Lyme arthritis facilitates easy assessment of Lyme borreliosis vaccine preparations for deleterious effects while murine models of severe destructive Lyme arthritis allow for investigation of mechanisms of immunopathology. PMID:22461836

Inhibitory effects of Zengshengping fractions on DMBA-induced buccal pouch carcinogenesis in hamsters.

Science.gov (United States)

Guan, Xiao-Bing; Sun, Zheng; Chen, Xiao-Xin; Wu, Hong-Ru; Zhang, Xin-Yan

2012-01-01

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. 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. 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 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. The n-butanol and water fractions of ZSP are effective at inhibiting tumor cell proliferation and stimulating apoptosis in oral cancer suggesting that these fractions have chemopreventive effects on DMBA induced oral carcinogenesis.

Radionuclide injury to the lung

International Nuclear Information System (INIS)

Dagle, G.E.; Sanders, C.L.

1984-01-01

Radionuclide injury to the lung has been studied in rats, hamsters, dogs, mice and baboons. Exposure of the lung to high dose levels of radionuclides produces a spectrum of progressively more severe functional and morphological changes, ranging from radiation pneumonitis and fibrosis to lung tumors. These changes are somewhat similar for different species. Their severity can be related to the absorbed radiation dose (measured in rads) produced by alpha, beta or gamma radiation emanating from various deposited radionuclides. The chemicophysical forms of radionuclides and spatial-temporal factors are also important variables. As with other forms of injury to the lung, repair attempts are highlighted by fibrosis and proliferation of pulmonary epithelium. Lung tumors are the principal late effect observed in experimental animals following pulmonary deposition of radionuclides at dose levels that do not result in early deaths from radiation pneumonitis or fibrosis. The predominant lung tumors described have been of epithelial origin and have been classified, in decreasing frequency of occurrence, as adenocarcinoma, bronchioloalveolar carcinoma, epidermoid carcinomas and combined epidermoid and adenocarcinoma. Mesothelioma and fibrosarcoma have been observed in rats, but less commonly in other species. Hemangiosarcomas were frequently observed in dogs exposed to beta-gamma emitters, and occasionally in rats exposed to alpha emitters. These morphologic changes in the lungs of experimental animals were reviewed and issues relevant to the prediction of human hazards discussed. 88 references

Mouse lung adhesion assay for Bordetella pertussis

Energy Technology Data Exchange (ETDEWEB)

Burns, K A; Freer, J H [Department of Microbiology, Alexander Stone Building, Bearsden, Glasgow, Scotland

1982-03-01

The ability of Bordetella pertussis to adhere to cell surfaces has been demonstrated by adhesion to tissue culture cells and adhesion to chicken, hamster or rabbit trachea in organ culture. In this report a mouse lung assay for adhesion is described and the results obtained using two virulent strains of B. pertussis and their avirulent counterparts. These were a C modulation of one of the original virulent strains and a phase IV variant of the other virulent strain. Organisms were radiolabelled by adding 1 ..mu..Ci (37 K Bq) of (/sup 14/C)glutamic acid per 10 ml of culture medium before inoculation and incubation for 5 days. The lungs were washed by perfusion in situ with at least two volumes (1 ml) of sterile 1% (w/v) casamino acids. The percentage of the inoculated organisms retained in the lungs was determined, after removal of the lungs, by one of the following two methods: viable count or radioactive count. Results for both methods were expressed as the percentage of the inoculum retained in the lungs plus or minus one standard deviation.

Mouse lung adhesion assay for Bordetella pertussis

International Nuclear Information System (INIS)

Burns, K.A.; Freer, J.H.

1982-01-01

The ability of Bordetella pertussis to adhere to cell surfaces has been demonstrated by adhesion to tissue culture cells and adhesion to chicken, hamster or rabbit trachea in organ culture. In this report a mouse lung assay for adhesion is described and the results obtained using two virulent strains of B. pertussis and their avirulent counterparts. These were a C modulation of one of the original virulent strains and a phase IV variant of the other virulent strain. Organisms were radiolabelled by adding 1 μCi (37 K Bq) of [ 14 C]glutamic acid per 10 ml of culture medium before inoculation and incubation for 5 days. The lungs were washed by perfusion in situ with at least two volumes (1 ml) of sterile 1% (w/v) casamino acids. The percentage of the inoculated organisms retained in the lungs was determined, after removal of the lungs, by one of the following two methods: viable count or radioactive count. Results for both methods were expressed as the percentage of the inoculum retained in the lungs plus or minus one standard deviation. (Auth.)

Cystolithiasis in a Syrian hamster: a different outcome | Petrini ...

African Journals Online (AJOL)

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. Keywords: Glucosamine, Hamster, Hesperidin, PEA, Urolithiasis ...

The effect of defective DNA double-strand break repair on mutations and chromosome aberrations in the Chinese hamster cell mutant XR-V15B

International Nuclear Information System (INIS)

Helbig, R.; Speit, G.; Zdzienicka, M.Z.

1995-01-01

The radiosensitive Chinese hamster cell line XR-V15B was used to study the effect of decreased rejoining of DNA double-strand breaks (DSBs) on gene mutations and chromosome aberrations. XR-V15B cells are hypersensitive to the cytotoxic effects of neocarzinostatin (NCS) and methyl methanesulfonate (MMS). Both mutagens induced more chromosome aberrations in XR-V15B cells than in the parental cell strain. The clastogenic action of NCS was characterized by the induction of predominantly chromosome-type aberrations in cells of both strains, whereas MMS induced mainly chromatid aberrations. The frequency of induced gene mutations at the hprt locus was not increased compared to the parental V79 cells when considering the same survival level. Molecular analysis by multiplex polymerase chain reaction (PCR) of mutants induced by NCS revealed a high frequency of deletions in cells of both cell lines. Methyl methane-sulfonate induced mainly mutations without visible change in the PCR pattern, which probably represent point mutations. Our findings suggest a link between a defect in DNA DSB repair and increased cytotoxic and clastogenic effects. However, a decreased ability to rejoin DNA DSBs does not seem to influence the incidence and types of gene mutations at the hprt locus induced by NCS and MMS. 28 refs., 4 figs., 3 tabs

Effects of a tumor promoter and an anti-promoter on spontaneous and UV-induced 6-thioguanine-resistant mutations and sister-chromatid exchanges in V79 Chinese hamster cells

International Nuclear Information System (INIS)

Fujiwara, Y.; Kano, Y.; Tatsumi, M.; Paul, P.

1980-01-01

The effects of a tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) and/or an anti-promoter antipain (protease inhibitor) on spontaneous and ultraviolet-induced sister-chromatid exchanges (SCEs) and 6-thioguanine-resistant (6TGsup(r)) recessive mutations were examined in V79 Chinese hamster cells in culture. TPA and/or antipain neither significantly altered base-line and UV-induced immediate SCE frequencies, nor decreased the level of delayed SCEs which persisted 6-7 days after irradiation. TPA and/or antipain appeared to enhance the recovery of UV-induced 6TGsup(r) colonies at the plateau expression phase despite non-mutagenicity by themselves and unaltered metabolic cooperation. Thus, the results conceivably imply that the 6TGsup(r)-recessive mutation expression, but not fixation, can be modulated at the cell level by TPA and/or antipain. Our results, together with the recent results of Loveday and Latt, may argue against the notion that TPA enhances the antipain-suppressible SCEs as an index of mitotic recombination in relevance with a tumor-promotion mechanism. (orig.)

Histopathology of Lyme arthritis in LSH hamsters

International Nuclear Information System (INIS)

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

1989-01-01

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

Fluoride does not induce DNA breakage in Chinese hamster ovary cells in vitro Flúor não induz danos ao DNA em células de ovário de hamster chinês in vitro

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Daniel Araki Ribeiro

2004-09-01

Full Text Available Fluoride has been widely used in dentistry because it is a specific and effective caries prophylactic agent. However, excess fluoride may represent a hazard to human health, especially by causing injury to genetic material. Genotoxicity tests represent an important part of cancer research to assess the risk of potential carcinogens. In the current study, the potential DNA damage associated with exposure to fluoride was assessed by the single cell gel (comet assay in vitro. Chinese hamster ovary cells were exposed to sodium fluoride (NaF at final concentration ranging from 7 to 100 µg/ml for 3 h, at 37°C. The results pointed out that NaF in all concentrations tested did not contribute to DNA damage as depicted by the mean tail moment and tail intensity. These findings are clinically important since they represent an important contribution to a correct evaluation of the potential health risk associated with the exposure to dental agents.O flúor tem sido amplamente usado na Odontologia, pois é um agente profilático efetivo e específico contra a cárie dentária. Entretanto, o flúor em excesso pode representar perigos à saúde humana, especialmente por causar agressão ao material genético. Testes de genotoxicidade representam uma importante parte da pesquisa do câncer para a avaliação de risco de possíveis carcinógenos. Neste presente estudo, danos ao DNA associados à exposição ao flúor foram avaliados pelo teste de células individualizadas em gel de agarose (teste do cometa in vitro. Células de ovário de hamster chinês foram expostas ao fluoreto de sódio (NaF nas concentrações finais de 7 a 100 µg/ml, durante 3 h, a 37°C. Os resultados mostraram que o NaF não contribuiu para os danos no DNA em todas as concentrações testadas, conforme demonstrado pelas médias do momento da cauda e da intensidade da cauda dos cometas. Esses achados são clinicamente importantes, uma vez que representam uma importante contribui

Treating advanced non-small-cell lung cancer in Chinese patients: focus on icotinib

Science.gov (United States)

Liang, Jun-Li; Ren, Xiao-Cang; Lin, Qiang

2014-01-01

Icotinib hydrochloride is an orally administered small-molecule reversible tyrosine kinase inhibitor that has been independently researched and developed and has independent intellectual property rights in the People’s Republic of China. Clinical trials have demonstrated that the response to icotinib among advanced non-small-cell lung cancer (NSCLC) patients who received at least one platinum-based chemotherapy regimen was not inferior to gefitinib. Since being launched August 2011 in the People’s Republic of China, icotinib has been widely used in clinics, and has become an important treatment option for Chinese patients with advanced NSCLC. The present study presents the Phase I, II, and III clinical trials of icotinib and discusses current clinical applications in the People’s Republic of China and future research directions. PMID:24876785

Photoperiodic regulation of the hamster testis: dependence on circadian rhythms

International Nuclear Information System (INIS)

Eskes, G.A.; Zucker, I.

1978-01-01

The testes of hamsters exposed to short days (10 hr of light per day) regress within 13 weeks. Administration of 7.5 percent deuterium oxide to hamsters lengthens the period of free running circadian activity rhythms by 2.2 percent and prevents testicular regression during short-day exposure. This is consistent with predictions derived from an external coincidence model for photoperiodic time measurement: Deuterium oxide changes phase relationships between the light-dark cycle and the circadian system, the hamster's daily photosensitive phase is stimulated with light during short days, and the testes remain large. Conservation of the period of circadian rhythms within narrow limits has adaptive significance for hamster photoperiodism and for the occurrence and phasing of the annual reproductive cycle

Development of Taenia pisiformis in golden hamster (Mesocricetus auratus

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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.

Metabolic influences on circadian rhythmicity in Siberian and Syrian hamsters exposed to long photoperiods.

Science.gov (United States)

Challet, E; Kolker, D E; Turek, F W

2000-01-01

Calorie restriction and other situations of reduced glucose availability in rodents alter the entraining effects of light on the circadian pacemaker located in the suprachiasmatic nuclei. Siberian and Syrian hamsters are photoperiodic species that are sexually active when exposed to long summer-like photoperiods, while both species show opposite changes in body mass when transferred from long to short or short to long days. Because metabolic cues may fine tune the photoperiodic responses via the suprachiasmatic nuclei, we tested whether timed calorie restriction can alter the photic synchronization of the light-entrainable pacemaker in these two hamster species exposed to long photoperiods. Siberian and Syrian hamsters were exposed to 16 h:8 h light:dark cycles and received daily hypocaloric (75% of daily food intake) or normocaloric diet (100% of daily food intake) 4 h after light onset. Four weeks later, hamsters were transferred to constant darkness and fed ad libitum. The onset of the nocturnal pattern of locomotor activity was phase advanced by 1.5 h in calorie-restricted Siberian hamsters, but not in Syrian hamsters. The lack of phase change in calorie-restricted Syrian hamsters was also observed in individuals exposed to 14 h:10 h dim light:dark cycles and fed with lower hypocaloric food (i.e. 60% of daily food intake) 2 h after light onset. Moreover, in hamsters housed in constant darkness and fed ad lib., light-induced phase shifts of the locomotor activity in Siberian hamsters, but not in Syrian hamsters were significantly reduced when glucose utilization was blocked by pretreatment with 500 mg/kg i.p. 2-deoxy-D-glucose. Taken together, these results show that the photic synchronization of the light-entrainable pacemaker can be modulated by metabolic cues in Siberian hamsters, but not in Syrian hamsters maintained on long days.

RTEL1 polymorphisms are associated with lung cancer risk in the Chinese Han population.

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Yan, Shouchun; Xia, Ridong; Jin, Tianbo; Ren, Hui; Yang, Hua; Li, Jing; Yan, Mengdan; Zhu, Yuanyuan; Chen, Mingwei

2016-10-25

RTEL1 (regulator of telomere elongation helicase 1; OMIM 608833) gene polymorphisms were linked to lung cancer (LC) susceptibility in a cancer genome-wide association study (GWAS) Here, we assessed whether seven previously reported RTEL1 polymorphisms influenced LC risk in Han Chinese population. All study samples (554 LC cases and 696 cancer-free controls) were collected from the Affiliated Hospital of Xizang Minzu University in China. We assessed associations between SNPs and LC risk using various several genetic models (codominant, dominant, recessive, overdominant, and additive). Whereas rs2738780 showed a protective effect against LC (Odds ratio (OR) = 0.80 ;95% confidence interval (CI): 0.638 = 0.998; p = 0.048), rs7261546(OR = 4.16; 95% CI: 1.35-12.82; p = 0.007), rs6062299(OR=5.08; 95% CI: 1.43-18.10; p = 0.005) and rs3787098(OR = 5.10; 95% CI: 1.43-18.15; p = 0.004) were all associated with increased LC susceptibility (recessive model). Haplotype analysis suggested that ''CTC'' was associated with a 0.8-fold decrease in LC risk (OR = 0.80, 95% CI, 0.63-1.00; Pearson's p = 0.05). These findings suggest a potential association between RTEL1 polymorphisms and LC risk in a Chinese Han population.

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...

The intrarenal distribution of 125I-albumin in the syrian hamster

International Nuclear Information System (INIS)

Moeller, P.

1977-01-01

The intrarenal distribution of radioiodinated human serum albumin ( 125 RISA) after intravenous injection was studied in Syrian hamsters by scintillation counting and frozen section autoradiogrpahy. After 15, 30, and 60 min the virtual plasma albumin space in the renal cortex of the hamster represented 6.49, 7.13, and 8.06% respectively of the kidney tissue volume. From the cortex to the renal papilla the albumin space increased to about 30% of the tissue volume. In comparison to this the albumin space in the renal cortex of the rat was about 20%, and in the renal papilla about 33% (11). Frozen section autoradiography indicated that the distribution of radioalbumin in the renal cortex if the Syrian hamster is limited mainly to the kidney vessels, being especially noticeable in the glomerular capillaries. Toward the papilla increasingly greater (mainly extratubular) activity could be observed not only intravascularly but also interstitially. In the cortex of the rat kidney, on the other hand, radioactive albumin was accumulated (probably by filtration and reabsorption) predominantly in the proximal tubular epithelium. Within 30 min the kidneys of the rat excreted more than 10 times as much 125 I than the hamster kidneys. These results (substantially less cortical accumulation and urinary excretion of radioalbumin in the Syrian hamster) indicate that, in contrast to the rat, obviously much less albumin is filtered (and then accumulated by proximal reabsorption) by the Syrian hamster glomeruli. This suggests that the Syrian hamster kidney is more suitable than the rat kidney for determining the interstitial, cortical, albumin space. (orig./AJ) [de

Genetic variant of miR-4293 rs12220909 is associated with susceptibility to non-small cell lung cancer in a Chinese Han population.

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Lixia Fan

Full Text Available Non-small cell lung cancer is one of the most common cancers and the leading cause of cancer death worldwide. Genetic variants in regulatory regions of some miRNAs might be involved in non-small cell lung cancer susceptibility and survival. rs12220909 (G/C genetic polymorphism in miR-4293 has been shown to be associated with decreased risk of esophageal squamous cell carcinoma. However, the influence of rs12220909 genetic variation on non-small cell lung cancer susceptibility has not been reported. In order to evaluate the potential association between miR-4293 rs12220909 and non-small cell lung cancer risk in a Chinese population, we performed a case-control study among 998 non-small cell lung cancer cases and 1471 controls. The data shows that miR-4293 rs12220909 was significantly associated with decreased susceptibility to non-small cell lung cancer (GC vs.GG: OR = 0.681, 95%CI = 0.555-0.835, P = 2.19E-4; GG vs. GC+CC: OR = 0.687, 95%CI = 0.564-0.837, P = 1.95E-4, which indicates that rs12220909 in miR-4293 may play a significant role in the development of non-small cell lung cancer.

Is there a progression-free survival benefit of first-line crizotinib versus standard chemotherapy and second-line crizotinib in ALK-positive advanced lung adenocarcinoma? A retrospective study of Chinese patients.

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Cui, Shaohua; Zhao, Yizhuo; Dong, Lili; Gu, Aiqin; Xiong, Liwen; Qian, Jialin; Zhang, Wei; Niu, Yanjie; Pan, Feng; Jiang, Liyan

2016-06-01

Although crizotinib has demonstrated promising efficacy and acceptable toxicity in patients with advanced non-small cell lung cancer (NSCLC), the available evidence in Chinese populations is currently limited. This study compared the progression-free survival (PFS) of Chinese patients with anaplastic lymphoma kinase (ALK)-positive, advanced lung adenocarcinoma who received first-line crizotinib therapy with that of patients who received first-line standard chemotherapy, and also the PFS benefit of first-line versus second-line crizotinib treatment. Data on 80 patients with ALK-positive, advanced lung adenocarcinoma who received crizotinib or standard chemotherapy as first-line treatments between June 2013 and December 2014 were retrospectively collected; 26 of the patients received crizotinib as second-line therapy after progressive disease (PD) occurred on first-line chemotherapy. Tumor responses were assessed using Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. The median PFS was 13.3 months (95% CI: 6.5-20.0 months) in patients who received first-line crizotinib as compared with 5.4 months (95% CI: 4.4-6.5 months) in patients who received first-line standard chemotherapy (adjusted hazard ratio for progression or death with crizotinib, 0.20; 95% CI: 0.11-0.36; P benefit of first-line crizotinib versus first-line standard chemotherapy in Chinese patients with ALK-positive lung adenocarcinoma. Additionally, crizotinib showed promising efficacy in patients who received it as second-line therapy after PD had occurred on first-line chemotherapy. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Nipah virus transmission in a hamster model.

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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.

Evidence for the induction of two types of potentially lethal damage after exposure of plateau phase Chinese hamster V79 cells to γ-rays

International Nuclear Information System (INIS)

Iliakis, G.

1985-01-01

The fixation of γ-rays induced potentially damage (PLD) caused after treatment either with β-araA or in medium made hypertonic by the addition of sodium chloride was studied in plateauphase chinese hamster V79 cells. Treatment with β-araA was found to affect a sector of PLD, the fixation of which specifically reduced the shoulder width of the survival curve. The effect was maximized when cell survival reached levels corresponding to an exponential line, with a slope similar to the final slope of the survival curve of untreated cells. This effect was achieved by a four hour treatment with β-araA at concentrations above 150 μM. Longer treatment times or incubation at higher β-araA concentrations did not significantly enhance the effect. Treatment in hypertonic medium, on the other hand, enhanced cell killing in a concentration dependent (NaCl-concentration) way and the survival reached values much lower than those corresponding to an exponential line. No indication for a plateau in the effect, indicating complete fixation of the sector of PLD that reacts sensitively to this treatment, was obtained. Boht the slope and the shoulder width of the survival curve were affected, the slope first being increaseed after short treatment times (up to 10 min), followed by a decrease in the shoulder width after longer treatment times (longer than 10 min). (orig./WL)

Isolation and cross-sensitivity of X-ray-sensitive mutants of V79-4 hamster cells

International Nuclear Information System (INIS)

Jones, N.J.; Cox, R.; Thacker, J.

1987-01-01

The V79-4 Chinese hamster line was mutagenized and surviving clones screened for X-ray sensitivity using a replica microwell technique. One slightly sensitive clone and 3 clearly sensitive clones were isolated from approximately 5000 screened, and designated irs 1 to irs 4. The 3 more sensitive clones showed different responses to the genotoxic agents mitomycin C (MMC), ethyl methanesulphonate (EMS) and ultraviolet light (UV). irs 1 showed considerable sensitivity to all the agents tested, in the order MMC >> EMS > UV. irs 2 and irs 3 had similar sensitivities to EMS and to UV (EMS > UV) but irs 3 was more sensitive than irs 2 to MMC. None of these mutants is identical in phenotype to previously published mutants. (Auth.)

Thermostability of sperm nuclei assessed by microinjection into hamster oocytes

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Nuclei isolated from spermatozoa of various species (golden hamster, mouse, human, rooster, and the fish tilapia) were heated at 60 degrees-125 degrees C for 20-120 min and then microinjected into hamster oocytes to determine whether they could decondense and develop into pronucl...

Black tea extract and dental caries formation in hamsters.

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Linke, Harald A B; LeGeros, Racquel Z

2003-01-01

Several studies have suggested that green tea and Oolong tea extracts have antibacterial and anticariogenic properties in vitro and in vivo. The aim of the present study was to determine the effect of a standardized black tea extract (BTE) on caries formation in inbred hamsters on a regular and a cariogenic diet. Eighty hamsters were divided into four groups of 20 animals each. Two groups received a pelleted regular diet (LabChow) with water or BTE ad libitum. The other two groups received a powdered cariogenic diet (Diet 2000, containing 56% sucrose) with water or BTE ad libitum. The animals were kept for 3 months on their respective diets and then were sacrificed. The heads were retained, the jaws were prepared and stained using alizarin mordant red II, and were then scored for dental caries according to the Keyes method. This is the first study indicating that BTE, as compared with water, significantly decreased caries formation by 56.6% in hamsters on a regular diet and by 63.7% in hamsters on a cariogenic diet (P cariogenic diet group BTE, reduced the mandibular caries score of the hamsters slightly more than the maxillary caries score. The fluoride content of the standardized BTE solution was frequently monitored during the experiment; the mean fluoride concentration was found to be 4.22 ppm. A frequent intake of black tea can significantly decrease caries formation, even in the presence of sugars in the diet.

The hamster flank organ model: Is it relevant to man

International Nuclear Information System (INIS)

Franz, T.J.; Lehman, P.A.; Pochi, P.; Odland, G.F.; Olerud, J.

1989-01-01

The critical role that androgens play in the etiology of acne has led to a search for topically active antiandrogens and the frequent use of the flank organ of the golden Syrian hamster as an animal model. 17-alpha-propyltestosterone (17-PT) has been identified as having potent antiandrogenic activity in the hamster model, and this report describes its clinical evaluation. Two double-blind placebo controlled studies comparing 4% 17-PT in 80% alcohol versus vehicle alone were conducted. One study examined 17-PT sebosuppressive activity in 20 subjects. The second study examined its efficacy in 44 subjects having mild to moderate acne. A third study measured in vitro percutaneous absorption of 17-PT through hamster flank and monkey skin, and human face skin in-vivo, using radioactive drug. 17-PT was found to be ineffective in reducing either the sebum excretion rate or the number of inflammatory acne lesions. Failure of 17-PT to show clinical activity was not a result of poor percutaneous absorption. Total absorption in man was 7.7% of the dose and only 1.0% in the hamster. The sebaceous gland of hamster flank organ is apparently more sensitive to antiandrogens than the human sebaceous gland

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

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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.

Infestivity of Demodex canis to hamster skin engrafted onto SCID mice.

Science.gov (United States)

Tani, Kenji; Une, Satoshi; Hasegawa, Atsuhiko; Adachi, Makoto; Kanda, Naoko; Watanabe, Shin-ichi; Nakaichi, Munekazu; Taura, Yasuho

2005-04-01

We demonstrated that Demodex canis was transferred to skin xenografts of a dog and a hamster onto severe combined immunodeficiency mice. After the transfer of mites, the number of eggs, larvae, nymphs and adult mites per gram of canine and hamster xenografts increased, whereas no live mites were detected on murine allograft. These results indicate that D. canis proliferates in hair follicles of dog and hamster skins but not in murine allograft. Therefore, D. canis may have host preference but not strict host-specificity.

Seasonal aspects of sleep in the Djungarian hamster

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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.

Cross-species transcriptomic approach reveals genes in hamster implantation sites.

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Lei, Wei; Herington, Jennifer; Galindo, Cristi L; Ding, Tianbing; Brown, Naoko; Reese, Jeff; Paria, Bibhash C

2014-12-01

The mouse model has greatly contributed to understanding molecular mechanisms involved in the regulation of progesterone (P4) plus estrogen (E)-dependent blastocyst implantation process. However, little is known about contributory molecular mechanisms of the P4-only-dependent blastocyst implantation process that occurs in species such as hamsters, guineapigs, rabbits, pigs, rhesus monkeys, and perhaps humans. We used the hamster as a model of P4-only-dependent blastocyst implantation and carried out cross-species microarray (CSM) analyses to reveal differentially expressed genes at the blastocyst implantation site (BIS), in order to advance the understanding of molecular mechanisms of implantation. Upregulation of 112 genes and downregulation of 77 genes at the BIS were identified using a mouse microarray platform, while use of the human microarray revealed 62 up- and 38 down-regulated genes at the BIS. Excitingly, a sizable number of genes (30 up- and 11 down-regulated genes) were identified as a shared pool by both CSMs. Real-time RT-PCR and in situ hybridization validated the expression patterns of several up- and down-regulated genes identified by both CSMs at the hamster and mouse BIS to demonstrate the merit of CSM findings across species, in addition to revealing genes specific to hamsters. Functional annotation analysis found that genes involved in the spliceosome, proteasome, and ubiquination pathways are enriched at the hamster BIS, while genes associated with tight junction, SAPK/JNK signaling, and PPARα/RXRα signalings are repressed at the BIS. Overall, this study provides a pool of genes and evidence of their participation in up- and down-regulated cellular functions/pathways at the hamster BIS. © 2014 Society for Reproduction and Fertility.

Astragalus-containing Traditional Chinese Medicine, with and without prescription based on syndrome differentiation, combined with chemotherapy for advanced non-small-cell lung cancer: a systemic review and meta-analysis.

Science.gov (United States)

Wang, S F; Wang, Q; Jiao, L J; Huang, Y L; Garfield, D; Zhang, J; Xu, L

2016-06-01

Traditional Chinese Medicine (tcm) is used in China as part of the treatment for non-small-cell lung cancer (nsclc) and often includes prescription of herbal therapy based on syndrome differentiation. Studies of various Astragalus-based Chinese medicines combined with platinum-based chemotherapy in the treatment of lung cancer are popular in East Asia, particularly in China. The aim of the present study was to perform a systematic review and meta-analysis comparing platinum-based chemotherapy alone with platinum-based chemotherapy plus Astragalus-based Chinese botanicals, with and without prescription based on syndrome differentiation, as first-line treatment for advanced nsclc. We searched the Chinese Biomedical Literature database, the China National Knowledge Internet, the VIP Chinese Science and Technology Periodicals Database, PubMed, embase, the Cochrane databases, and abstracts presented at meetings of the American Society of Clinical Oncology, the World Conference on Lung Cancer, the European Society for Medical Oncology, and the Chinese Society of Clinical Oncology for all eligible studies. Endpoints were overall survival; 1-year, 2-year, and 3-year survival rates; performance status; overall response rate; and grade 3 or 4 adverse events. Subgroup analyses based on herbal formulae individualized using syndrome differentiation or on oral or injection patent medicines were performed using the Stata software application (version 11.0: StataCorp LP, College Station, TX, U.S.A.) and a fixed-effects or random-effects model in case of heterogeneity. Results are expressed as a hazard ratio (hr) or relative risk (rr), with corresponding 95% confidence intervals (cis). Seventeen randomized studies with scores on the Jadad quality scale of 2 or more, representing 1552 patients, met the inclusion criteria. Compared with platinum-based chemotherapy alone, the addition of Astragalus-based tcm to chemotherapy was associated with significantly increased overall survival

Phosphatidylserine biosynthesis in cultured Chinese hamster ovary cells. I. Inhibition of de novo phosphatidylserine biosynthesis by exogenous phosphatidylserine and its efficient incorporation

International Nuclear Information System (INIS)

Nishijima, M.; Kuge, O.; Akamatsu, Y.

1986-01-01

The effect of phosphatidylserine exogenously added to the medium on de novo biosynthesis of phosphatidylserine was investigated in cultured Chinese hamster ovary cells. When cells were cultured for several generations in medium supplemented with phosphatidylserine and 32 Pi, the incorporation of 32 Pi into cellular phosphatidylserine was remarkably inhibited, the degree of inhibition being dependent upon the concentration of added phosphatidylserine. 32 Pi uptake into cellular phosphatidylethanolamine was also partly reduced by the addition of exogenous phosphatidylserine, consistent with the idea that phosphatidylethanolamine is biosynthesized via decarboxylation of phosphatidylserine. However, incorporation of 32 Pi into phosphatidylcholine, sphingomyelin, and phosphatidylinositol was not significantly affected. In contrast, the addition of either phosphatidylcholine, sphingomyelin, phosphatidylethanolamine, or phosphatidylinositol to the medium did not inhibit endogenous biosynthesis of the corresponding phospholipid. Radiochemical and chemical analyses of the cellular phospholipid composition revealed that phosphatidylserine in cells grown with 80 microM phosphatidylserine was almost entirely derived from the added phospholipid. Phosphatidylserine uptake was also directly determined by using [ 3 H]serine-labeled phospholipid. Pulse and pulse-chase experiments with L-[U- 14 C] serine showed that when cells were cultured with 80 microM phosphatidylserine, the rate of synthesis of phosphatidylserine was reduced 3-5-fold. Enzyme assaying of extracts prepared from cells grown with and without phosphatidylserine indicated that the inhibition of de novo phosphatidylserine biosynthesis by the added phosphatidylserine appeared not to be caused by a reduction in the level of the enzyme involved in the base-exchange reaction between phospholipids and serine

Lung injury-dependent oxidative status and chymotrypsin-like activity of skeletal muscles in hamsters with experimental emphysema.

Science.gov (United States)

Tonon, Jair; Cecchini, Alessandra Lourenço; Brunnquell, Cláudia Roberta; Bernardes, Sara Santos; Cecchini, Rubens; Guarnier, Flávia Alessandra

2013-01-23

Peripheral skeletal muscle is altered in patients suffering from emphysema and chronic obstructive pulmonary disease (COPD). Oxidative stress have been demonstrated to participate on skeletal muscle loss of several states, including disuse atrophy, mechanical ventilation, and chronic diseases. No evidences have demonstrated the occurance in a severity manner. We evaluated body weight, muscle loss, oxidative stress, and chymotrypsin-like proteolytic activity in the gastrocnemius muscle of emphysemic hamsters. The experimental animals had 2 different severities of lung damage from experimental emphysema induced by 20 mg/mL (E20) and 40 mg/mL (E40) papain. The severity of emphysema increased significantly in E20 (60.52 ± 2.8, p < 0.05) and E40 (52.27 ± 4.7; crossed the alveolar intercepts) groups. As compared to the control group, there was a reduction on body (171.6 ± 15.9 g) and muscle weight (251.87 ± 24.87 mg) in the E20 group (157.5 ± 10.3 mg and 230.12 ± 23.52 mg, for body and muscle weight, respectively), which was accentuated in the E40 group (137.4 ± 7.2 g and 197.87 ± 10.49 mg, for body and muscle weight, respectively). Additionally, the thiobarbituric acid reactive substances (TBARS), tert-butyl hydroperoxide-initiated chemiluminescence (CL), carbonylated proteins, and chymotrypsin-like proteolytic activity were elevated in the E40 group as compared to the E20 group (p < 0.05 for all comparisons). The severity of emphysema significantly correlated with the progressive increase in CL (r = -0.95), TBARS (r = -0.98), carbonyl proteins (r = -0.99), and chymotrypsin-like proteolytic activity (r = -0.90). Furthermore, augmentation of proteolytic activity correlated significantly with CL (r = 0.97), TBARS (r = 0.96), and carbonyl proteins (r = 0.91). Taken together, the results of the present study suggest that muscle atrophy observed in this model of emphysema is mediated by increased muscle chymotrypsin-like activity, with possible involvement of

Aryl- and alkyl-phosphorus-containing flame retardants induced mitochondrial impairment and cell death in Chinese hamster ovary (CHO-k1) cells

International Nuclear Information System (INIS)

Huang, Chao; Li, Na; Yuan, Shengwu; Ji, Xiaoya; Ma, Mei; Rao, Kaifeng; Wang, Zijian

2017-01-01

Phosphorus-containing flame retardants (PFRs) are increasingly in demand worldwide as replacements for brominated flame retardants (BFRs), but insufficient available toxicological information on PFRs makes assessing their health risks challenging. Mitochondria are important targets of various environmental pollutants, and mitochondrial dysfunction may lead to many common diseases. In the present study, mitochondria impairment-related endpoints were measured by a high content screening (HCS) assay for 11 selected non-halogen PFRs in Chinese hamster ovary (CHO-k1) cells. A cluster analysis was used to categorize these PFRs into three groups according to their structural characteristics and results from the HCS assay. Two groups, containing long-chain alkyl-PFRs and all aryl-PFRs, were found to cause mitochondrial impairment but showed different mechanisms of toxicity. Due to the high correlation between cell death and mitochondrial impairment, two PFRs with different structures, trihexyl phosphate (THP) and cresyl diphenyl phosphate (CDP), were selected and compared with chlorpyrifos (CPF) to elucidate their mechanism of inducing cell death. THP (an alkyl-PFR) was found to utilize a similar pathway as CPF to induce apoptosis. However, cell death induced by CDP (an aryl-PFR) was different from classical necrosis based on experiments to discriminate among the different modes of cell death. These results confirm that mitochondria might be important targets for some PFRs and that differently structured PFRs could function via distinct mechanisms of toxicity. - Highlights: • Mitochondrial impairment induced by PFRs was observed in CHO-k1 cells. • THP (an alkyl-PFR) induced a caspase-mediated apoptosis in CHO-k1 cells. • The cell death induced by CDP (an aryl-PFR) was not traditional apoptosis or necrosis.

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

International Nuclear Information System (INIS)

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

1988-01-01

The effects of β-chloroalanine (β-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 β-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 β-Cl-alanine and this treatment inhibited [ 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 β-Cl-alanine appeared to occur with little perturbation of other cell functions: the cells exhibited no loss in cell viability, [ 14 C]serine uptake was not blocked, total lipid biosynthesis from [ 14 C]acetic acid was not decreased (nor was the appearance of radiolabel in cholesterol and phosphatidylcholine), and [ 3 H]thymidine incorporation into DNA was not affected. There appeared to be little effect on protein synthesis based on the incorporation of [ 3 H]leucine, which was only decreased by 14%. Although β-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 β-Cl-alanine and other mechanism-based inhibitors might be useful to study alterations in cellular long-chain base synthesis

The influence of the wavelength of ultraviolet radiation on survival, mutation induction and DNA repair in irradiated Chinese hamster cells

International Nuclear Information System (INIS)

Zelle, B.; Reynolds, R.J.; Kottenhagen, M.J.; Schuite, A.; Lohmann, P.H.M.

1980-01-01

Chinese hamster ovary cells were used to compare the cytotoxicity and mutagenicity of far-UV radiation emitted by a low-pressure mercury, germicidal lamp (wavelength predominantly 254 nm) with that of near UV radiation emitted by a fluorescent lamp with a continuous spectrum (Westinghouse Sun Lamp), of which only the radiation with wavelengths greater than 290 nm or greater than 310 nm was transmitted to the cells. The radiation effects were compared on the basis of an equal number of pyrimidine dimers, the predominant lesion induced in DNA by far-UV, for the induction of which much more energy is needed with near-UV than with 254-nm radiation. The numbers of dimers induced were determined by a biochemical method detecting UV-endonuclease-susceptible sites. The equivalence of these sites with pyrimidine dimers was established, qualitatively and quantitatively, in studies with enzymic photoreactivation in vitro and chromatographic analysis of dimers. On the basis of induced dimers, more cells were killed by UE 310-nm UV than by UE 290-nm UV; both forms of radiation were more cytotoxic than 254-nm UV when equal numbers of dimers were induced. Moreover, 5-6 times as many mutants were induced per dimer by UE 310-nm UV than by UE 290-nm UV; the latter appeared approximately as mutagenic as 254-nm UV. The differences in lethality and mutagenicity were not caused by differences in repair of dimers: cells with an equal number of dimers induced by either 254-nm or near-UV showed the same removal of sites susceptible to a UV endonuclease specific for dimers, as well as an identical amount of repair replication. The results indicate that near-UV induces, besides pyrimidine dimers, other lesions that appear to be of high biological significance. (orig.)

Subchronic inhalation of carbon tetrachloride alters the tissue retention of acutely inhaled plutonium-239 nitrate in F344 rats and syrian golden hamsters

International Nuclear Information System (INIS)

Benson, J.M.; Barr, E.B.; Lundgren, D.L.

1995-01-01

Carbon tetrachloride (CCl 4 ) has been used extensively in the nuclear weapons industry, so it is likely that nuclear plant workers have been exposed to both CCl 4 and plutonium compounds. Future exposures may occur during open-quotes cleanupclose quotes operations at weapons productions sites such as the Hanford, Washington, and Rocky Flats, Colorado, facilities. Inhalation of 20 and 100 ppm CCl 4 by hamsters reduces uptake of 239 Pu solubilized from lung, shunting the 239 Pu to the skeleton

Arnica Tincture Cures Cutaneous Leishmaniasis in Golden Hamsters

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Sara M. Robledo

2018-01-01

Full Text Available In search for potential therapeutic alternatives to existing treatments for cutaneous Leishmaniasis, we have investigated the effect of Arnica tincture Ph. Eur. (a 70% hydroethanolic tincture prepared from flowerheads of Arnica montana L. on the lesions caused by infection with Leishmania braziliensis in a model with golden hamsters. The animals were treated topically with a daily single dose of the preparation for 28 days. Subsequently, the healing process was monitored by recording the lesion size in intervals of 15 days up to day 90. As a result, Arnica tincture fully cured three out of five hamsters while one animal showed an improvement and another one suffered from a relapse. This result was slightly better than that obtained with the positive control, meglumine antimonate, which cured two of five hamsters while the other three showed a relapse after 90 days. This result encourages us to further investigate the potential of Arnica tincture in the treatment of cutaneous Leishmaniasis.

ROS-mediated genotoxicity of asbestos-cement in mammalian lung cells in vitro

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Rödelsperger Klaus

2005-10-01

Full Text Available Abstract Asbestos is a known carcinogen and co-carcinogen. It is a persisting risk in our daily life due to its use in building material as asbestos-cement powder. The present study done on V79-cells (Chinese hamster lung cells demonstrates the cytotoxic and genotoxic potential of asbestos-cement powder (ACP in comparison with chrysotile asbestos. A co-exposure of chrysotile and ACP was tested using the cell viability test and the micronucleus assay. The kinetochore analysis had been used to analyse the pathway causing such genotoxic effects. Thiobarbituric acid-reactive substances were determined as evidence for the production of reactive oxygen species. Both, asbestos cement as well as chrysotile formed micronuclei and induced loss of cell viability in a concentration- and time- dependent way. Results of TBARS analysis and iron chelator experiments showed induction of free radicals in ACP- and chrysotile exposed cultures. CaSO4 appeared to be a negligible entity in enhancing the toxic potential of ACP. The co-exposure of both, ACP and chrysotile, showed an additive effect in enhancing the toxicity. The overall study suggests that asbestos-cement is cytotoxic as well as genotoxic in vitro. In comparison to chrysotile the magnitude of the toxicity was less, but co-exposure increased the toxicity of both.

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 Welfare...

EGFR Mutations in Surgically Resected Fresh Specimens from 697 Consecutive Chinese Patients with Non-Small Cell Lung Cancer and Their Relationships with Clinical Features

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Yuanyang Lai

2013-12-01

Full Text Available We aimed to reveal the true status of epidermal growth factor receptor (EGFR mutations in Chinese patients with non-small cell lung cancer (NSCLC after lung resections. EGFR mutations of surgically resected fresh tumor samples from 697 Chinese NSCLC patients were analyzed by Amplification Refractory Mutation System (ARMS. Correlations between EGFR mutation hotspots and clinical features were also explored. Of the 697 NSCLC patients, 235 (33.7% patients had tyrosine kinase inhibitor (TKIs sensitive EGFR mutations in 41 (14.5% of the 282 squamous carcinomas, 155 (52.9% of the 293 adenocarcinomas, 34 (39.5% of the 86 adenosquamous carcinomas, one (9.1% of the 11 large-cell carcinomas, 2 (11.1% of the 18 sarcomatoid carcinomas, and 2 (28.6% of the 7 mucoepidermoid carcinomas. TKIs sensitive EGFR mutations were more frequently found in female patients (p < 0.001, non-smokers (p = 0.047 and adenocarcinomas (p < 0.001. The rates of exon 19 deletion mutation (19-del, exon 21 L858R point mutation (L858R, exon 21 L861Q point mutation (L861Q, exon 18 G719X point mutations (G719X, including G719C, G719S, G719A were 43.4%, 48.1%, 1.7% and 6.8%, respectively. Exon 20 T790M point mutation (T790M was detected in 3 squamous carcinomas and 3 adenocarcinomas and exon 20 insertion mutation (20-ins was detected in 2 patients with adenocarcinoma. Our results show the rates of EGFR mutations are higher in all types of NSCLC in Chinese patients. 19-del and L858R are two of the more frequent mutations. EGFR mutation detection should be performed as a routine postoperative examination in Chinese NSCLC patients.

Development of a model system to study leukotriene-induced modification of radiation sensitivity in mammalian cells

Energy Technology Data Exchange (ETDEWEB)

Walden, Jr, T L; Holahan, Jr, E V; Catravas, G N

1986-01-01

Leukotrienes (LT) are an important class of biological mediators for which no information exists concerning their synthesis following a radiation insult or on their ability to modify cellular response to a subsequent radiation exposure. Results are presented which illustrate that the Chinese hamster lung fibroblast cell line, V79A03, is useful as a model system to study the metabolic fate of leukotrienes and the effect of LT on radiation sensitivity of mammalian cells in vitro. (U.K.).

Effects of agonist efficacy on desensitization of phosphoinositide hydrolysis mediated by m1 and m3 muscarinic receptors expressed in Chinese hamster ovary cells

International Nuclear Information System (INIS)

Hu, J.; Wang, S.Z.; el-Fakahany, E.E.

1991-01-01

Muscarinic receptor agonist-induced desensitization of phosphoinositide (PI) hydrolysis and loss of receptors were studied in Chinese hamster ovary (CHO) cells transfected with the m1 and m3 muscarinic receptor genes. Long-term exposure to the full agonist carbamylcholine (CBC) resulted in a time-dependent attenuation of the maximal PI response and a decrease in agonist potency. This desensitization was accompanied by a parallel loss of maximal ligand binding without an alteration of the binding affinity. The time course of both receptor desensitization and down-regulation was similar in m1 and m3 CHO cells. The PI response to the partial agonist McN-A-343 (McN) in m1 cells was more sensitive to desensitization by CBC than the response to the latter agonist, and this desensitization was faster than receptor down-regulation. Desensitization of the PI response to McN was reflected as a decrease in the maximal response without a marked change in potency. McN induced slow desensitization of the PI response to CBC but a much faster desensitization of its own response. Our data provide evidence that although muscarinic agonist-induced desensitization of PI hydrolysis in CHO cells is due mainly to loss of receptors, there are other important factors which play a role in this process, e.g., receptor-effector uncoupling. The relative contribution of these different mechanisms depends on the efficacy of the agonists used for the receptor desensitization and activation steps

Kisspeptin and the seasonal control of reproduction in hamsters

DEFF Research Database (Denmark)

Simonneaux, Valérie; Ansel, Laura; Revel, Florent G

2008-01-01

-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 arcuate nucleus of the Syrian hamster is lower in short photoperiod, when animals are sexually quiescent. Notably, intracerebroventricular infusion of Kiss1 gene product, kisspeptin, in hamsters kept in short photoperiod is able to override the inhibitory photoperiod and to reactivate sexual activity...

[An experimental study on the Chinese lung adenocarcinoma cell clone CPA-Yang1-BR with brain metastasis potency in nude mice and in vivo imaging research].

Science.gov (United States)

Lei, Bei; Cao, Jie; Shen, Jie; Zhao, Lanxiang; Liang, Sheng; Meng, Qinggang; Xie, Wenhui; Yang, Shunfang

2013-08-20

Lung cancer is the leading cause of cancer-related death in men and women. It is also the most common cause of brain metastases. A brain metastasis model is difficult to be established because of the presence of the blood-brain barrier (BBB) and the lack of optimal methods for detecting brain metastasis in nude mice. Thus, the establishment of a Chinese lung adenocarcinoma cell line and its animal model with brain metastasis potency and in vivo research is of great significance. CPA-Yang1 cells were obtained from a patient with human lung adenocarcinoma by lentiviral vector-mediated transfection of green fluorescence protein. Intracardiac inoculation of the cells was performed in nude mice, and brain metastatic lesions were detected using micro ¹⁸F FDG-PET/CT scanners, small animal in vivo imaging system for fluorescence, radionuclide and X ray fused imaging, magnetic resonance imaging (MRI) with sense body detection, and resection. The samples were divided into two parts for cell culture and histological diagnosis. The process was repeated in vivo and in vitro for four cycles to obtain a novel cell clone, CPA-Yang1-BR. A novel cell clone, CPA-Yang1-BR, was obtained with a brain metastatic rate of 50%. The use of MRI for the detection of brain metastases has obvious advantages. An experimental Chinese lung adenocarcinoma cell clone (CPA-Yang1-BR) and its animal model with brain metastasis potency in nude mice were established. MRI with sense body or micro MRI may be used as a sensitive, accurate, and noninvasive method to detect experimental brain metastases in intact live immunodeficient mice. The results of this study may serve as a technical platform for brain metastases from lung adenocarcinoma.

Respiratory tract tumors in Syrian hamsters following inhalation of Pu--ZrO2 particles

International Nuclear Information System (INIS)

Thomas, R.G.; Smith, D.M.

1979-01-01

Inhalation of radionuclide-bearing particles remains one of the most intensely pursued problems concerning the nuclear industry. This route of entry is generally accepted as the most probable, in case of human exposure, with ingestion being the other prominent source of concern. Many laboratory investigations, such as those reported here, continue to evaluate the possible consequences that may present health problems to the public domain. Syrian hamsters of both sexes received either inhaled (INH) PuO 2 /ZrO 2 particles, intravenous (IV) PuO 2 /ZrO 2 microspheres, a combination of INH PuO 2 /ZrO 2 particles and injected PuO 2 /ZrO 2 microspheres, or no radionuclides (controls). The INH particles and IV microspheres were tagged with γ-emitting 57 Co to facilitate whole body counting and establishment of retention curves. Total lung burdens ranged from 8 nCi to 143 nCi. Significant numbers of primary lung tumors (5 to 50% per group) were induced in those animals that received INH exposures. Additional α radiation administered via Pu-laden IV microspheres had little or no effect on tumor production or nonneoplastic, degenerative changes in the respiratory tract

Biological alterations resulting from chronic lung irradiation. III. Effect of partial 60Co thoracic irradiation upon pulmonary collagen metabolism and fractionation in syrian hamsters

International Nuclear Information System (INIS)

Pickrell, J.A.; Harris, D.V.; Hahn, F.F.; Belasich, J.J.; Jones, R.K.

1975-01-01

Radiation-induced changes in pulmonary collagen metabolism were studied in Syrian hamsters given multiple thoracic doses of 60 Co radiation to achieve cumulative exposures of 6000, 4000, and 2000 R. At 13 to 14 wk after initial exposure, 6000- and 4000-R exposures had increased incorporation of injected [ 14 C]proline into pulmonary collagenous protein which suggested an increased collagen synthesis. By 21 to 22 wk after exposure, increased pulmonary soluble collagen was noted. Increased pulmonary scarring was indicated by a variable increase in native collagen at 13 to 36 wk. A collection of alveolar macrophages at 7 to 8 wk followed by inflammation at 13 to 14 wk and a beginning of pulmonary fibrosis at 13 to 19 wk were noted. At 21 to 22 wk after exposure a somewhat more marked pulmonary fibrosis and some epithelialization were observed. Hemosiderin deposits were also observed at 35 to 36 wk after exposure, but pathologic processes were lessened by this time. The early activation of collagen synthesis presumably caused the radiation-induced fibrosis. Later, when collagen tended to accumulate, the synthetic rate was normal. The activation of collagen synthesis caused by external thoracic irradiation resembles that caused by thoracic irradiation from the internal emitter, 144 Ce. Moreover, it demonstrates the usefulness of monitoring collagen biosynthesis by [ 14 C]proline incorporation into the lung. (U.S.)

Subchronic inhalation of carbon tetrachloride alters the tissue retention of acutely inhaled plutonium-239 nitrate in F344 rats and syrian golden hamsters

Energy Technology Data Exchange (ETDEWEB)

Benson, J.M.; Barr, E.B.; Lundgren, D.L. [and others

1995-12-01

Carbon tetrachloride (CCl{sub 4}) has been used extensively in the nuclear weapons industry, so it is likely that nuclear plant workers have been exposed to both CCl{sub 4} and plutonium compounds. Future exposures may occur during {open_quotes}cleanup{close_quotes} operations at weapons productions sites such as the Hanford, Washington, and Rocky Flats, Colorado, facilities. Inhalation of 20 and 100 ppm CCl{sub 4} by hamsters reduces uptake of {sup 239}Pu solubilized from lung, shunting the {sup 239}Pu to the skeleton.

Establishment of A Novel Chinese Human Lung Adenocarcinoma Cell Line CPA-Yang3 and Its Real Bone Metastasis Clone CPA-Yang3BM in Immunodeficient Mice

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Shunfang YANG

2011-02-01

Full Text Available Background and objective The recurrence and metastasis of lung cancer is a tough problem worldwide. The aim of this study is to establish a novel Chinese lung adenocarcinoma cell line and its real bone-seeking clone sub-line for exploring the molecular mechanism of lung cancer metastasis. Methods The cells came from the pleural effusion of a sixtyfive years old female patient with lung adenocarcinoma and supraclavicular lymph node metastases. The gene expression was detected by real-time quantitative PCR. Intracardiac injection of the cells into nude mice was performed and in vivo imaging was obtained by bone scintigraphy and conventional radiography. Bone metastases were determined on bone scintigraphy and then the lesions were resected under deep anesthesia for bone metastasis cancer cell culture. The process was repeated for four cycles to obtain a real bone-seeking clone. Results The tumorigenesis rate started at 4th passage in immunodeficient mice via subcutaneously and as well as later passages. Approximately 1×106 cancer cells were injected into left cardiac ventricle of immunodeficient mice resulted bone metastasis sites were successfully revealed by bone scintigraphy and pathological diagnosis, the mandible (100%, scapula (33%, humerus (50%, vertebral column (50%, femur (66.7% and accompanied invasion with other organs, the adrenal gland (17%, pulmonary (33%, liver (50%, submaxillary gland (33% in the mice after inoculation two-three weeks. The chromosome karyotype analysis of the cells was subdiploid. Quantitative real-time PCR was used to examined and compared with SPC-A-1 lung adenocarcinoma, ESM1, VEGF-C, IL-6, IL-8, AR, SVIL, FN1 genes were overexpress. The novel cell was named CPA-Yang3. The femur metastasis cell was repeated in vivo-in vitro-in vivo with three cycles and harvested a real bone metastasis clone. It was named CPA-Yang3BM. Conclusion Tne characteristics of novel strain CPAYang3 is a highly metastasis cell line of

An investigation of the genetic toxicology of irradiated food-stuffs using short-term test systems

International Nuclear Information System (INIS)

Renner, H.W.; Altmann, H.; Asquith, J.C.; Elias, P.S.

1982-01-01

Six in vivo genetic toxicity tests were carried out on irradiated or unirradiated cooked chicken, dried dates and cooked fish. The tests were as follows: sex-linked recessive lethal mutations in Drosophila melanogaster (dried dates only), chromosome aberrations in bone marrow of Chinese hamsters, micronucleus test in rats, mice and Chinese hamsters, sister-chromatid exchange in bone marrow of mice and Chinese hamsters and in spermatogonia of mice, and DNA metabolism in spleen cells of Chinese hamsters. None of the tests provided any evidence of genetic toxicity induced by irradiation. However, dried dates, whether irradiated or not, showed evidence of some genetic toxicity in their effect on DNA metabolism in spleen cells and SCE induction in bone marrow. Feeding irradiated fish affected DNA metabolism in the spleen cells of Chinese hamsters. This effect could be interpreted as an induction of an immunoactive compound, although it could also be explained by the persistence of an immunoactive compound due to the removal by irradiation of spoilage organisms that would normally degrade it. (author)

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

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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.

Photoperiod history differentially impacts reproduction and immune function in adult Siberian hamsters.

Science.gov (United States)

Prendergast, Brian J; Pyter, Leah M

2009-12-01

Seasonal changes in numerous aspects of mammalian immune function arise as a result of the annual variation in environmental day length (photoperiod), but it is not known if absolute photoperiod or relative change in photoperiod drives these changes. This experiment tested the hypothesis that an individual's history of exposure to day length determines immune responses to ambiguous, intermediate-duration day lengths. Immunological (blood leukocytes, delayed-type hypersensitivity reactions [DTH]), reproductive, and adrenocortical responses were assessed in adult Siberian hamsters (Phodopus sungorus) that had been raised initially in categorically long (15-h light/day; 15L) or short (9L) photoperiods and were subsequently transferred to 1 of 7 cardinal experimental photoperiods between 9L and 15L, inclusive. Initial photoperiod history interacted with contemporary experimental photoperiods to determine reproductive responses: 11L, 12L, and 13L caused gonadal regression in hamsters previously exposed to 15L, but elicited growth in hamsters previously in 9L. In hamsters with a 15L photoperiod history, photoperiods history, DTH responses were largely unaffected by increases in day length. Enhancement and suppression of blood leukocyte concentrations occurred at 13L in hamsters with photoperiod histories of 15L and 9L, respectively; however, prior exposure to 9L imparted marked hysteresis effects, which suppressed baseline leukocyte concentrations. Cortisol concentrations were only enhanced in 15L hamsters transferred to 9L and, in common with DTH, were unaffected by photoperiod treatments in hamsters with a 9L photoperiod history. Photoperiod history acquired in adulthood impacts immune responses to photoperiod, but manifests in a markedly dissimilar fashion as compared to the reproductive system. Prior photoperiod exposure has an enduring impact on the ability of the immune system to respond to subsequent changes in day length.

Lung cancer in Asian women - the environment and genes

Energy Technology Data Exchange (ETDEWEB)

Lam, W.K. [University of Hong Kong, Pokfulam (China). Queen Mary Hospital

2005-09-15

The mortality rate of lung cancer in Asian women has increased significantly in the past few decades. Environmental factors include tobacco smoke (active and environmental), other indoor pollutions (cooking oil vapours, coal burning, fungus spores), diet, and infections. Active tobacco smoking is not the major factor. Cooking oil vapours associated with high temperature wok cooking and indoor coal burning for heating and cooking in unvented homes, particularly in rural areas, are risk factors for Chinese women. Chronic benign respiratory diseases due to the fungus Microsporum canis probably accounts for the high incidence of lung cancer in northern Thai women at Sarapee. Diets rich in fruits, leafy green vegetables, and vitamin A are protective, while cured meat (Chinese sausage, pressed duck and cured pork), deep-fried cooking, and chili increased the risk. Tuberculosis is associated with lung cancer. Also, a Taiwanese study showed that the odds ratio of papillomavirus (HPV) 16/18 infection in non-smoking female lung cancer patients was 10.1, strongly suggesting a causative role. Genetic factors have also been studied in Chinese women, including human leucocyte antigens, K-ras oncogene activation, p53 mutation, polymorphisms of phase I activating enzymes (cytochrome P450, N-acetyltransferase slow acetylator status), and phase II detoxifying enzymes (glutathione-S-transferases, N-acetyltransferase rapid acetylator status).

A Syrian golden hamster model recapitulating ebola hemorrhagic fever.

Science.gov (United States)

Ebihara, Hideki; Zivcec, Marko; Gardner, Donald; Falzarano, Darryl; LaCasse, Rachel; Rosenke, Rebecca; Long, Dan; Haddock, Elaine; Fischer, Elizabeth; Kawaoka, Yoshihiro; Feldmann, Heinz

2013-01-15

Ebola hemorrhagic fever (EHF) is a severe viral infection for which no effective treatment or vaccine is currently available. While the nonhuman primate (NHP) model is used for final evaluation of experimental vaccines and therapeutic efficacy, rodent models have been widely used in ebolavirus research because of their convenience. However, the validity of rodent models has been questioned given their low predictive value for efficacy testing of vaccines and therapeutics, a result of the inconsistent manifestation of coagulopathy seen in EHF. Here, we describe a lethal Syrian hamster model of EHF using mouse-adapted Ebola virus. Infected hamsters displayed most clinical hallmarks of EHF, including severe coagulopathy and uncontrolled host immune responses. Thus, the hamster seems to be superior to the existing rodent models, offering a better tool for understanding the critical processes in pathogenesis and providing a new model for evaluating prophylactic and postexposure interventions prior to testing in NHPs.

Evaluation of Efficacy and Safety of Bevacizumab Combined with Chemotherapy 
for Chinese Patients with Advanced Non-small Cell Lung Cancer

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Xiao ZHAO

2012-01-01

Full Text Available Background and objective The current study reported the result of bevacizumab treatment administered to 25 Chinese patients with advanced non-small cell lung cancer (NSCLC who were treated at the Peking Union Medical College Hospital as a part of the SAiL (MO19390 trial. This trial is an open, international multicenter, single-arm clinical study that assesses the safety and efficacy of first-line bevacizumab-based therapy in advanced NSCLC. Methods Twenty-five Chinese patients with advanced non-squamous NSCLC received bevacizumab (15 mg/kg combined with chemotherapy (carboplatin plus paclitaxel treatment from August 2007 to February 2008. Adverse effects (AEs, objective response rate (ORR, median time to progression (TTP, and overall survival (OS were measured. Results AEs were generally mild and reversible. The most frequent AEs were alopecia, peripheral neuropathy, rash, proteinuria, nausea/vomitting, fatigue, myalgia, bleeding, and hypertension. The partial remission and stable disease rates were 68% and 28%, respectively. The median TTP and OS of all patients were 11.2 and 19.3 months, respectively. Conclusion Bevacizumab combined with carboplatin-based chemotherapy may be well tolerated and beneficial for Chinese patients with non-squamous NSCLC.

Dopamine mediates testosterone-induced social reward in male Syrian hamsters.

Science.gov (United States)

Bell, Margaret R; Sisk, Cheryl L

2013-03-01

Adolescent maturation of responses to social stimuli is essential for adult-typical sociosexual behavior. Naturally occurring developmental changes in male Syrian hamster responses to a salient social cue, female hamster vaginal secretions (VS), provide a good model system for investigating neuroendocrine mechanisms of adolescent change in social reward. Sexually naïve adult, but not juvenile, males show a conditioned place preference (CPP) to VS, indicating that VS is not rewarding before puberty. In this series of experiments, the authors examined the roles of testosterone and dopamine receptor activation in mediating the adolescent gain in positive valence of VS. Experiment 1 showed that testosterone replacement is necessary for gonadectomized adult hamsters to form a CPP to VS. Experiment 2 showed that testosterone treatment is sufficient for juvenile hamsters to form a CPP to VS, and that the dopamine receptor antagonist haloperidol blocks formation of a CPP to VS in these animals. Experiments 3 and 4 demonstrated that the disruption of VS CPP with low doses of haloperidol is the result of a reduction in the attractive properties of VS and not attributable to aversive properties of haloperidol. Together, these studies demonstrate that the unconditioned rewarding properties of a social cue necessary for successful adult sociosexual interactions come about as the result of the pubertal increase in circulating testosterone in male hamsters. Furthermore, this social reward can be prevented by dopamine receptor antagonism, indicating that hypothalamic and/or mesocorticolimbic dopaminergic circuits are targets for hormonal activation of social reward.

Syrian Hamster as an Animal Model for the Study of Human Influenza Virus Infection.

Science.gov (United States)

Iwatsuki-Horimoto, Kiyoko; Nakajima, Noriko; Ichiko, Yurie; Sakai-Tagawa, Yuko; Noda, Takeshi; Hasegawa, Hideki; Kawaoka, Yoshihiro

2018-02-15

Ferrets and mice are frequently used as animal models for influenza research. However, ferrets are demanding in terms of housing space and handling, whereas mice are not naturally susceptible to infection with human influenza A or B viruses. Therefore, prior adaptation of human viruses is required for their use in mice. In addition, there are no mouse-adapted variants of the recent H3N2 viruses, because these viruses do not replicate well in mice. In this study, we investigated the susceptibility of Syrian hamsters to influenza viruses with a view to using the hamster model as an alternative to the mouse model. We found that hamsters are sensitive to influenza viruses, including the recent H3N2 viruses, without adaptation. Although the hamsters did not show weight loss or clinical signs of H3N2 virus infection, we observed pathogenic effects in the respiratory tracts of the infected animals. All of the H3N2 viruses tested replicated in the respiratory organs of the hamsters, and some of them were detected in the nasal washes of infected animals. Moreover, a 2009 pandemic (pdm09) virus and a seasonal H1N1 virus, as well as one of the two H3N2 viruses, but not a type B virus, were transmissible by the airborne route in these hamsters. Hamsters thus have the potential to be a small-animal model for the study of influenza virus infection, including studies of the pathogenicity of H3N2 viruses and other strains, as well as for use in H1N1 virus transmission studies. IMPORTANCE We found that Syrian hamsters are susceptible to human influenza viruses, including the recent H3N2 viruses, without adaptation. We also found that a pdm09 virus and a seasonal H1N1 virus, as well as one of the H3N2 viruses, but not a type B virus tested, are transmitted by the airborne route in these hamsters. Syrian hamsters thus have the potential to be used as a small-animal model for the study of human influenza viruses. Copyright © 2018 American Society for Microbiology.

Sensibility of the hamster (Cricetus auratus to the Treponema pertenue

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F. Nery-Guimarães

1955-05-01

Full Text Available In two experiments, 8 Hamsters inoculated with material from yaws lesions (Treponema pertenue, developed skin lesions considered specific by their clinical and histopathological aspects and by the presence of treponemae. These lesions appeared on the scrotumm, testicle, prepuce, anus, tail, muzzle, back and hinders paws (palm surface. In the internal organs no treponemae were found in direct examinations and inoculation of brain, spleen and lymph node. The incubation period was of 35 days for the testicle, 55 days for the scrotum and 107 days for peritoneal cavity inoculation. Positive sub-inoculations were obtained. The serum reactions (Qasserman's and Kahn's were negative in all 5 tested Hamsters. Out of 4 normal females matched to infected males two developed nasal lesions resulting from direct contact. Apparently the genital lesions hindered copulation. Hamsters are very well suited for an experimental study of yaws.Em 2 experiências, 8 Hamsters inoculados com material direto de lesões boubáticas (Treponema pertenue, desenvolveram lesões cutâneas consideradas específicas, pelo aspecto clínico e histopatológico e pela presentça de treponemas. Essas lesões se manifestaram no escrôto, testículo, prepúcio, anus, cauda, focinho, dorso e patas posteriores (face palmar. Nos órgãos internos não foram vistos treponemas ao exame direto e, uma vez, por inoculação de cérebro, baço e gânglio linfático. O período incubativo foi de 35 dias pela via testicular, 55 dias pela via escrotal e 107 dias pela via peritonial. Foram obtidas sub-inoculações positivas para Hamsters normais. As experiências continuam. De 4 fêmeas normais, acasaladas com 4 hamsters infectados apenas 2 mostraram lesões positivas resultantes de contágio direto. Aparentemente, não houve copulação e, se esta ocorreu, não determinou fecundação.

Is FDG PET/CT cost-effective for pre-operation staging of potentially operative non-small cell lung cancer? - From Chinese healthcare system perspective

Energy Technology Data Exchange (ETDEWEB)

Wang, Yu-ting, E-mail: wangyuting_330@163.com [Department of Nuclear Medicine, Renji Hospital, Shanghai Jiao Tong University, School of Medicine (China); Huang, Gang, E-mail: huang2802@163.com [Department of Nuclear Medicine, Renji Hospital, Shanghai Jiao Tong University, School of Medicine (China); Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) and Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences - CAS (China)

2012-08-15

Objectives: The remarkable morbidity and mortality of lung cancer in the large population address major economic challenges to Chinese healthcare system. This study aims to assess the cost-effectiveness of fluorodeoxyglucose positron emission tomography (FDG PET)/CT for staging patients with non-small cell lung cancer (NSCLC) in China. Methods: Management of potentially operative NSCLC was modeled on decision analysis employing data in China. The strategies compared were conventional CT staging (strategy A), additional PET/CT in all patients (strategy B) or only in patients with normal-sized lymph nodes on CT (strategy C). Published medical data for Chinese patients was extracted. The costs corresponded to reimbursement by Chinese public health provider in 2010. Uncertainly of employed parameters was calculated in sensitivity analysis. Results: Taking strategy A as baseline, the incremental cost-effectiveness ratio (ICER) of strategy B was 23,800 RMB ($3500) per life year saved, which was acceptable in views of a developing country as China; while strategy C exhibited some loss of life years. Sensitivity analysis suggested the ICER (B-A) was raised more remarkably by a deterioration of PET specificity than by that of its sensitivity. The ICER was turned negative by PET specificity lower than 0.79. Economically, PET cost was proportional to the ICER (B-A), and decrease of palliative therapy cost could reduce both the ICER and overall cost. Conclusions: The PET/CT strategy is potentially cost-effective for management of NSCLC in China. Patients with nodal-positive CT results are not suggested to be excluded from further PET/CT. Furthermore, maintaining high specificity of PET in clinical scenarios is crucial. Prospective trials are warranted to transfer these results into policy making.

Genetic variants of JNK and p38α pathways and risk of non-small cell lung cancer in an Eastern Chinese population.

Science.gov (United States)

Jia, Ming; Zhu, Meiling; Zhou, Fei; Wang, Mengyun; Sun, Menghong; Yang, Yajun; Wang, Xiaofeng; Wang, Jiucun; Jin, Li; Xiang, Jiaqing; Zhang, Yawei; Chang, Jianhua; Wei, Qingyi

2017-02-15

The JNK and p38α pathways play an important role in carcinogenesis. Therefore, we hypothesize that single nucleotide polymorphisms (SNPs) of genes involved in these pathways are associated with risk of lung cancer. We first selected and genotyped 11 independent SNPs of the JNK and p38α pathway-related genes in a discovery set of 1,002 non-small cell lung cancer (NSCLC) cases and 1,025 cancer-free controls of Eastern Chinese. Then, we validated those significant SNPs in a replication set of 1,333 NSCLC cases and 1,339 cancer-free controls of Eastern Chinese. Multifactor dimensionality reduction (MDR) and classification and regression tree (CART) analyses were used to identify interactions between significant SNPs and other covariates. In both discovery and replication as well as their pooled analysis, carriers of GADD45G rs8252T variant genotypes had a significantly lower risk of NSCLC (adjusted OR = 0.81 and 0.79, 95% CI = 0.72-0.92 and 0.64-0.99 and p = 0.001 and 0.040 for dominant and recessive genetic models, respectively) and carriers of MAP2K7 rs3679T variant genotypes had an increased risk of NSCLC (adjusted OR = 1.19 and 1.29, 95% CI = 1.05-1.34 and 1.09-1.54 and p = 0.005 and 0.004 for dominant and recessive genetic models, respectively). Furthermore, rs8252 variant CT/TT carriers showed significantly higher levels of GADD45G mRNA expression than CC carriers in the target tissues. We observed some evidence of interactions between rs8252 genotypes and sex in NSCLC risk. These results indicate that GADD45G rs8252 and MAP2K7 rs3679 SNPs may be susceptibility biomarkers for NSCLC in Eastern Chinese populations. © 2016 UICC.

Hamsters' (Mesocricetus auratus) memory in a radial maze analog: the role of spatial versus olfactory cues.

Science.gov (United States)

Tonneau, François; Cabrera, Felipe; Corujo, Alejandro

2012-02-01

The golden hamster's (Mesocricetus auratus) performance on radial maze tasks has not been studied a lot. Here we report the results of a spatial memory task that involved eight food stations equidistant from the center of a circular platform. Each of six male hamsters depleted the food stations along successive choices. After each choice and a 5-s retention delay, the hamster was brought back to the center of the platform for the next choice opportunity. When only one baited station was left, the platform was rotated to evaluate whether olfactory traces guided hamsters' choices. Results showed that despite the retention delay hamsters performed above chance in searching for food. The choice distributions observed during the rotation probes were consistent with spatial memory and could be explained without assuming guidance by olfactory cues. The radial maze analog we devised could be useful in furthering the study of spatial memory in hamsters.

Effect of microdose distribution on chromosome aberration frequency in liver cells of the Chinese hamster following exposure to 239PuO2 or 238PuO2 particles

International Nuclear Information System (INIS)

Brooks, A.L.; Peters, R.F.; Retherford, J.C.

1974-01-01

Chinese hamsters were injected intravenously with 239 PuO 2 or 238 PuO 2 particles of known size or with 238 Pu citrate to determine the effect of particle size and specific activity on the frequency and distribution of chromosome damage in the liver. Three particle sizes were used in the 239 PuO 2 experiment: 0.15, 0.44, and 0.89 μm, and all animals were injected with a constant activity, 5 x 10 -4 muCi 239 Pu/gm body weight. The 238 PuO 2 was injected in three particle sizes, 0.17, 0.41, and 1.1 μm and at three activity levels. The 238 Pu citrate was injected at 5 x 10 -3 muCi 238 Pu/gm body weight. Hamsters injected with 239 PuO 2 were sacrificed at 15, 42, and 122 days after injection and those injected with either 238 PuO 2 or 238 Pu citrate were sacrificed 12 days after injection. The number of alpha tracks/star increased as a function of the particle size injected. A change in particle size with time was noted as smaller particles were aggregated into larger ones by the phagocytic action of Kupffer cells. Injection of 239 PuO 2 and 238 PuO 2 produced a distribution of chromosome damage which was non-poison in nature. 239 PuO 2 produced increased damage with increasing average dose with some cells containing a large number of aberrations, but there was relatively little particle size effect. Conversely, aberration frequencies after 238 PuO 2 injection were inversely related to particle size and no cells were seen with large amounts of damage. The 238 Pu citrate produced 6 x 10 -3 aberrations/cell/rad which was a higher rate than observed for 238 Pu particles. Risk for the production of cellular damage in the liver was greater per μCi following injection of either 238 Pu or 239 Pu citrate than it was following deposition of the same amount of 239 PuO 2 or 238 PuO 2 particles. (U.S.)

[Purification of arsenic-binding proteins in hamster plasma after oral administration of arsenite].

Science.gov (United States)

Wang, Wenwen; Zhang, Min; Li, Chunhui; Qin, Yingjie; Hua, Naranmandura

2013-01-01

To purify the arsenic-binding proteins (As-BP) in hamster plasma after a single oral administration of arsenite (iAs(III)). Arsenite was given to hamsters in a single dose. Three types of HPLC columns, size exclusion, gel filtration and anion exchange columns, combined with an inductively coupled argon plasma mass spectrometer (ICP MS) were used to purify the As-BP in hamster plasma. SDS-PAGE was used to confirm the arsenic-binding proteins at each purification step. The three-step purification process successfully separated As-BP from other proteins (ie, arsenic unbound proteins) in hamster plasma. The molecular mass of purified As-BP in plasma was approximately 40-50 kD on SDS-PAGE. The three-step purification method is a simple and fast approach to purify the As-BP in plasma samples.

Secondhand smoke induces hepatic apoptosis and fibrosis in hamster fetus.

Science.gov (United States)

Huang, Chien-Wei; Horng, Chi-Ting; Huang, Chih-Yang; Cho, Ta-Hsiung; Tsai, Yi-Chang; Chen, Li-Jeng; Hsu, Tsai-Ching; Tzang, Bor-Show

2016-09-01

Secondhand smoke (SHS) is an important health issue worldwide. Inhaling SHS during pregnancy could cause abnormalities in the internal tissues of newborns, which may then impair fetal development and even cause severe intrauterine damage and perinatal death. However, the understanding of cytopathic mechanisms of SHS by maternal passive smoking on fetus liver during pregnancy is still limited. This study analyzed the effects of high-dose SHS (SHSH) on fetus liver using a maternal passive smoking animal model. Experiments showed that hepatic matrix metalloproteinase-9 activity and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling-positive cells were significantly increased in livers from fetuses of hamsters treated with SHSH. Similarly, expressions of both extrinsic and intrinsic apoptotic molecules were significantly higher in livers from fetuses of hamsters exposed to SHSH. Additionally, significantly increased inflammatory proteins, including transforming growth factor β, inducible nitric oxide synthase, and interleukin 1β, and fibrotic signaling molecules, including phosphorylated Smad2/3, SP1, and α-smooth muscle actin, were observed in the fetus livers from hamsters treated with SHSH. This study revealed that SHSH not only increased apoptosis through intrinsic and extrinsic pathways in the livers of fetuses from hamsters exposed to SHSH but also augmented hepatic fibrosis via Smad2/3 signaling. © The Author(s) 2015.

A new species of Giardia Künstler, 1882 (Sarcomastigophora: Hexamitidae) in hamsters.

Science.gov (United States)

Lyu, Zhangxia; Shao, Jingru; Xue, Min; Ye, Qingqing; Chen, Bing; Qin, Yan; Wen, Jianfan

2018-03-20

Giardia spp. are flagellated protozoan parasites that infect humans and many other vertebrates worldwide. Currently seven species of Giardia are considered valid. Here, we report a new species, Giardia cricetidarum n. sp. in hamsters. Trophozoites of G. cricetidarum n. sp. are pear-shaped with four pairs of flagella and measure on average 14 μm (range 12-18 μm) in length and 10 μm (range 8-12 μm) in width. The trophozoites of the new species are generally larger and stouter than those of most of the other Giardia spp. and exhibit the lowest length/width ratio (c.1.40) of all recognized Giardia species. Cysts of G. cricetidarum n. sp. are ovoid and measure on average 11 μm (range 9-12 μm) in length and 10 μm (range 8-10 μm) in width and are indistinguishable from the cysts of other Giardia species. Molecular phylogenetic analyses based on beta-giardin, small subunit rRNA, and elongation factor-1 alpha loci all demonstrated that G. cricetidarum n. sp. is genetically distinct from all currently accepted Giardia spp. Investigation of the host range indicated that the new species was only found in hamsters (including Phodopus sungorus, P. campbelli and Mesocricetus auratus), while all the other described mammal-parasitizing species (G. muris, G. microti and G. intestinalis) each infect multiple hosts. Cross-transmission studies further demonstrated the apparent host specificity of G. cricetidarum n. sp. as it only infected hamsters. Trophozoites were found in high numbers in hamster intestines (5 × 10 5 - 5 × 10 6 ) and was rarely detected co-infecting with other Giardia spp. in the common hamster, suggesting it has some advantages in parasitizing hamsters. This study has identified a new species of Giardia, which appears to be specific to hamsters, and together with the three other mammal-parasitizing Giardia species with different host ranges, may be able to be used as a model system for the study of evolutionary divergence of host parasitism strategies in

Association Between Four Polymorphisms in lncRNA and Risk of Lung Cancer in a Chinese Never-Smoking Female Population.

Science.gov (United States)

Gao, Min; Li, Hang; Lv, Xiaoting; Zhou, Baosen; Yin, Zhihua

2018-06-07

Long noncoding RNAs (lncRNAs) play important roles in the development of human cancers. This is the first case-control study of the association between specific polymorphisms in lncRNA genes and the risk of lung cancer, as well as the gene-environment interaction between the polymorphisms and cooking oil fume exposure in Chinese never-smoking females. A hospital-based case-control study was carried out in Shenyang, Liaoning province. The study included 395 cases and 556 controls. The polymorphisms of rs4785367, rs3803662, rs10750417, and rs1814343 in lncRNA genes were analyzed. The gene-environment interactions were explored on both additive and multiplicative scale. In addition, the results were listed as follows: for rs3803662, compared with the individuals carrying homozygous TT genotype, those with homozygous CC genotype had the decreased risk of lung cancer (adjusted odds ratio [OR] = 0.61, 95% confidence interval [CI] = 0.40-0.92, p = 0.018). As for rs4785367, compared with homozygous TT, homozygous CC could lessen the risk of lung cancer (adjusted OR = 0.54, 95% CI = 0.33-0.89, p = 0.016). The recessive models of rs3803662 and rs4785367 showed significant association (adjusted OR = 0.65, 95% CIs = 0.44-0.97, p = 0.033; adjusted OR = 0.54, 95% CIs = 0.33-0.88, p = 0.014). The C allele of rs3803662 was suggested to be protective allele of lung cancer (adjusted OR = 0.80, 95% CI = 0.66-0.97, p = 0.023). However, rs10750417 and rs1814343 polymorphisms were not significantly associated with lung cancer risks. The measures of additive interaction and logistic models suggested that the gene-environment interactions were not statistically significant on both additive and multiplicative scales.

Inverse dose-rate effect for the induction of 6-thioguanine-resistant mutants in Chinese hamster V79-S cells by 60Co gamma rays

International Nuclear Information System (INIS)

Crompton, N.E.; Barth, B.; Kiefer, J.

1990-01-01

Chinese hamster V79-S cells capable of growing in suspension culture were exposed to 60Co gamma rays at a high dose rate (84 Gy/h), low dose rates (200, 50, and 39 mGy/h), and a spectrum of very low dose rates (between 29 and 4.5 mGy/h). Following time for appropriate expression the cultures were assayed for the induction of 6-thioguanine-resistant mutants. For a given dose, a decrease in mutation induction occurred as the dose rate was reduced from high dose rates to low dose rates. However, further reduction in dose rate resulted in a reverse dose-rate effect, and an increase in the frequency of mutants was observed. The contribution of background mutation frequency to this reverse dose-rate effect was studied, both by examining fluctuations of mutation frequency in nonirradiated culture and by its impact upon the dose-rate-independent nature of the reversed effect, and it was found to be negligible. The physiological state of the suspension culture under periods of protracted exposure to very low dose rates was also investigated. The effect of doubling time, plating efficiency, cell cycle distribution, and sensitivity on survival and mutation were examined. In no case was a change apparent during the very low-dose-rate exposures. The results are discussed in terms of the possible expression of cryptic radiation damage after prolonged culture times and/or the involvement of an error-free repair system which requires a certain amount of radiation damage to become active

Induction of DNA double-strand breaks by restriction enzymes in X-ray-sensitive mutant Chinese hamster ovary cells measured by pulsed-field gel electrophoresis

International Nuclear Information System (INIS)

Kinashi, Yuko; Nagasawa, Hatsumi; Little, J.B.; Okayasu, Ryuichi; Iliakis, G.E.

1995-01-01

This investigation was designed to determine whether the cytotoxic effects of different restriction endonucleases are related to the number and type of DNA double-strand breaks (DSBs) they produce. Chinese hamster ovary (CHO) K1 and xrs-5 cells, a radiosensitive mutant of CHO K1, were exposed to restriction endonucleases HaeIII, HinfI, PvuII and BamHI by electroporation. These enzymes represent both blunt and sticky end cutters with differing recognition sequence lengths. The number of DSBs was measured by pulsed-field gel electrophoresis (PFGE). Two forms of PFGE were employed: asymmetric field-inversion gel electrophoresis (AFIGE) for measuring the kinetics of DNA breaks by enzyme digestion and clamped homogeneous gel electrophoresis (CHEF) for examining the size distributions of damaged DNA. The amount of DNA damage induced by exposure to all four restriction enzymes was significantly greater in xrs-5 compared to CHO K1 cells, consistent with the reported DSB repair deficiency in these cells. Since restriction endonucleases produce DSBs alone as opposed to the various types of DNA damage induced by X rays, these results confirm that the repair defect in this mutant involves the rejoining of DSBs. Although the cutting frequency was directly related to the length of the recognition sequence for four restriction enzymes, there was no simple correlation between the cytotoxic effect and the amount of DNA damage produced by each enzyme in either cell line. This finding suggests that the type or nature of the cutting sequence itself may play a role in restriction enzyme-induced cell killing. 32 refs., 6 figs., 3 tabs

Chinese Medicine Treatment for Afatinib-Induced Paronychia

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Pei-Yuu Yang

2017-01-01

Full Text Available Afatinib (Gilotrif™ is widely used to treat patients with mutant activating epidermal growth factor receptor- (EGFR- dependent lung adenocarcinoma; however, it has various adverse side effects. Here, we report a patient with afatinib-induced paronychia. After Chinese medicine treatment with the well-known anticancer Chinese herbs, Jen-Ren-Hwo-Minq-Saan, and decoction of Ban-Zhi-Lian (Scutellaria barbata with Bai-Hua-She-She-Cao (Hedyotis diffusa Willd, patient’s condition was significantly improved. This shows that these Chinese medicines can not only be used in cancer treatment but also be used in the afatinib-induced paronychia.

Effects of hyperthermia on the hamster immune system

International Nuclear Information System (INIS)

Gangavalli, R.; Cain, C.A.; Tompkins, W.A.F.

1984-01-01

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 (41 0 C; 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

Diurnal rhythms in gonadotropins and progesterone in lactating and photoperiod induced acyclic hamsters

International Nuclear Information System (INIS)

Bridges, R.S.; Goldman, B.D.

1975-01-01

Levels of LH, FSH, and progesterone in serum were measured in lactating hamsters and in hamsters in which acyclicity was induced with altered photoperiod. Lactating hamsters were found to have low titers of LH, FSH, and progesterone in serum at 0900 (lights on 0500--1900) on Days 4, 9, 14, and 19 of lactation and increased levels of these hormones at 1600. Levels of LH and FSH in serum at both 0900 and 1600 remained relatively constant throughout lactation. In contrast, levels of progesterone in serum obtained at both 0900 and 1600 sampling times increased as lactation progressed. Ovariectomy on Day 9 of lactation reduced serum levels of progesterone at both 0900 and 1600 and eliminated the afternoon surge in progesterone in animals bled 5 days after surgery. The levels and pattern of LH in serum remained unchanged after ovariectomy in lactating hamsters. However, serum FSH levels in the ovariectomized, lactating animals were elevated at both 0900 and 1600 when compared to levels present in intact, lactating hamsters bled at the same times. Females which were acyclic due to altered photoperiod displayed similar patterns of LH, FSH, and progesterone in serum. Levels of LH, FSH, and progesterone in serum were low at 1000 (lights on 0500--1500) and were increased 2 to 10 fold at 1500. Ovariectomy was followed by lower progesterone levels in serum at 1000 and 1500 and eliminated the afternoon rise of this hormone. Serum levels of LH were unaffected by ovariectomy. As in lactating hamsters, levels of FSH in serum were elevated 3--4 days following ovariectomy at both bleeding times, but the levels were higher at 1500. These results indicate that acyclicity induced by lactation or exposure to a short photoperiod is characterized by similar diurnal patterns of circulating hormones in the hamster

Autoradiographic localization of tritiated dihydrotestosterone in the flank organ of the albino hamster

International Nuclear Information System (INIS)

Lucky, A.W.; Eisenfeld, A.J.; Visintin, I.

1985-01-01

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 ( [ 3 H]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. [ 3 H]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 [ 3 H]DHT in animals pretreated with excessive quantities of unlabeled DHT. Steroid metabolites of [ 3 H] 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

Impact of wheel running on chronic ethanol intake in aged Syrian hamsters.

Science.gov (United States)

Brager, Allison J; Hammer, Steven B

2012-10-10

Alcohol dependence in aging populations is seen as a public health concern, most recently because of the significant proportion of heavy drinking among "Baby Boomers." Basic animal research on the effects of aging on physiological and behavioral regulation of ethanol (EtOH) intake is sparse, since most of this research is limited to younger models of alcoholism. Here, EtOH drinking and preference were measured in groups of aged Syrian hamsters. Further, because voluntary exercise (wheel-running) is a rewarding substitute for EtOH in young adult hamsters, the potential for such reward substitution was also assessed. Aged (24 month-old) male hamsters were subjected to a three-stage regimen of free-choice EtOH (20% v/v) or water and unlocked or locked running wheels to investigate the modulatory effects of voluntary wheel running on EtOH intake and preference. Levels of fluid intake and activity were recorded daily across 60 days of experimentation. Prior to wheel running, levels of EtOH intake were significantly less than levels of water intake, resulting in a low preference for EtOH (30%). Hamsters with access to an unlocked running wheel had decreased EtOH intake and preference compared with hamsters with access to a locked running wheel. These group differences in EtOH intake and preference were sustained for up to 10 days after running wheels were re-locked. These results extend upon those of our previous work in young adult hamsters, indicating that aging dampens EtOH intake and preference. Voluntary wheel running further limited EtOH intake, suggesting that exercise could offer a practical approach for managing late-life alcoholism. Copyright © 2012 Elsevier Inc. All rights reserved.

[Four properties law of nature data of Chinese materia medica in "Chinese herbal medicine (CHM)"].

Science.gov (United States)

Yang, Xue-Mei; Lin, Duan-Yi; Lai, Xin-Mei; Chen, Mei-Mei; Huang, Lu-Qi

2013-05-01

In order to provide theoretical clues and data support for the use of Chinese medicine clinical drug, experimental study of Chinese materia medica and development of new resources of Chinese materia medica, the four properties as the core, the relationships of property, flavor, channel tropism and toxicity in nature data of Chinese materia medica were analyzed. The spearman rank correlation method was employed to analyze 8 356 Chinese drugs with characteristic of four properties from " Chinese Herbal Medicine" based on data level coding. It was discovered that four properties showed significant positive correlations with tastes of "pungent and sweet" , channels of "spleen" , "stomach" , "kidney" and "toxicity" , but also showed significant negative correlations with tastes of "bitter" and "light" and six channels such as "large intestine" , "heart", "bladder" , "gallbladder" , "small intestine" and "lung" (in descending order of correlation ) (P <0. 01). It was indicated that the more hot the Chinese medicine nature, the more possible it contained "toxicity" , tastes of "pungent" and "sweet" , and the more possible it was belong to channels of "spleen" , "stomach" and "kidney". As well, the more cold the Chinese medicine nature, the more possible it contained tastes of "bitter" and "light", and the more possible it was belong to six channels such as "large intestine", etc.

Functional evidence for alternative ANG II-forming pathways in hamster cardiovascular system

NARCIS (Netherlands)

Nishimura, H; Buikema, H; Baltatu, O; Ganten, D; Urata, H

1998-01-01

Like human chymase, hamster chymase is an ANG II-forming enzyme, but pathophysiological roles of chymase are still unknown. We determined the functional conversion of ANG I and [Pro(11), D-Ala(12)]ANG I, a chymase-selective substrate, to ANG II in the hamster cardiovascular system. ANG I and

Is FDG PET/CT cost-effective for pre-operation staging of potentially operative non-small cell lung cancer? – From Chinese healthcare system perspective

International Nuclear Information System (INIS)

Wang, Yu-ting; Huang, Gang

2012-01-01

Objectives: The remarkable morbidity and mortality of lung cancer in the large population address major economic challenges to Chinese healthcare system. This study aims to assess the cost-effectiveness of fluorodeoxyglucose positron emission tomography (FDG PET)/CT for staging patients with non-small cell lung cancer (NSCLC) in China. Methods: Management of potentially operative NSCLC was modeled on decision analysis employing data in China. The strategies compared were conventional CT staging (strategy A), additional PET/CT in all patients (strategy B) or only in patients with normal-sized lymph nodes on CT (strategy C). Published medical data for Chinese patients was extracted. The costs corresponded to reimbursement by Chinese public health provider in 2010. Uncertainly of employed parameters was calculated in sensitivity analysis. Results: Taking strategy A as baseline, the incremental cost-effectiveness ratio (ICER) of strategy B was 23,800 RMB ($3500) per life year saved, which was acceptable in views of a developing country as China; while strategy C exhibited some loss of life years. Sensitivity analysis suggested the ICER (B–A) was raised more remarkably by a deterioration of PET specificity than by that of its sensitivity. The ICER was turned negative by PET specificity lower than 0.79. Economically, PET cost was proportional to the ICER (B–A), and decrease of palliative therapy cost could reduce both the ICER and overall cost. Conclusions: The PET/CT strategy is potentially cost-effective for management of NSCLC in China. Patients with nodal-positive CT results are not suggested to be excluded from further PET/CT. Furthermore, maintaining high specificity of PET in clinical scenarios is crucial. Prospective trials are warranted to transfer these results into policy making.

Diet-induced metabolic hamster model of nonalcoholic fatty liver disease

Directory of Open Access Journals (Sweden)

Bhathena J

2011-06-01

Full Text Available Jasmine Bhathena, Arun Kulamarva, Christopher Martoni, Aleksandra Malgorzata Urbanska, Meenakshi Malhotra, Arghya Paul, Satya PrakashBiomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering, Artificial Cells and Organs Research Centre, Faculty of Medicine, McGill University, Montreal, Québec, CanadaBackground: Obesity, hypercholesterolemia, elevated triglycerides, and type 2 diabetes are major risk factors for metabolic syndrome. Hamsters, unlike rats or mice, respond well to diet-induced obesity, increase body mass and adiposity on group housing, and increase food intake due to social confrontation-induced stress. They have a cardiovascular and hepatic system similar to that of humans, and can thus be a useful model for human pathophysiology.Methods: Experiments were planned to develop a diet-induced Bio F1B Golden Syrian hamster model of dyslipidemia and associated nonalcoholic fatty liver disease in the metabolic syndrome. Hamsters were fed a normal control diet, a high-fat/high-cholesterol diet, a high-fat/high-cholesterol/methionine-deficient/choline-devoid diet, and a high-fat/high-cholesterol/choline-deficient diet. Serum total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, glucose, atherogenic index, and body weight were quantified biweekly. Fat deposition in the liver was observed and assessed following lipid staining with hematoxylin and eosin and with oil red O.Results: In this study, we established a diet-induced Bio F1B Golden Syrian hamster model for studying dyslipidemia and associated nonalcoholic fatty liver disease in the metabolic syndrome. Hyperlipidemia and elevated serum glucose concentrations were induced using this diet. Atherogenic index was elevated, increasing the risk for a cardiovascular event. Histological analysis of liver specimens at the end of four weeks showed increased fat deposition in the liver of animals fed

Effects of light deprivation on prolactin regulation in the Golden Syrian hamster

International Nuclear Information System (INIS)

Massa, J.S.

1986-01-01

Pineal-mediated depressions in prolactin cell activity after light deprivation were studied in the male and female Golden Syrian hamster. Prolactin cell activity was determined by measuring radioimmunoassayable prolactin, newly synthesized prolactin, newly synthesized prolactin and prolactin mRNA levels in the pituitary. Serum prolactin was also measured by radioimmunoassay. Use of the recombinant DNA plasmid, pPRL-1, which contains the rat prolactin complimentary DNA sequence, was validated in this dissertation for measuring prolactin mRNA in the hamster. Male Hamsters blinded for 11, 21, or 42 days showed significant and progressively greater declines in prolactin mRNA levels which were completely prevented by pinealectomy. Female hamsters blinded for 28 days, however, showed no such decreases in prolactin cell activity if they continued to display estrous cyclicity. After 12 weeks of blinding, females were acyclic and had dramatically depressed levels of prolactin cell activity. However, pinealectomy did not completely prevent this decline due to blinding unless the females continue to display estrous cyclicity. In ovariectomized females, blinding caused a decline in prolactin cell activity. In a separate study, significant changes in prolactin cell activity during the estrous cycle were seen in untreated normally cycling female hamsters. These changes in prolactin mRNA, prolactin synthesis, and radioimmunoassayable prolactin in the pituitary were measured in the morning, when, consistent with other reports, no differences in serum prolactin were observed

Vasopressin differentially modulates aggression and anxiety in adolescent hamsters administered anabolic steroids.

Science.gov (United States)

Morrison, Thomas R; Ricci, Lesley A; Melloni, Richard H

2016-11-01

Adolescent Syrian hamsters (Mesocricetus auratus) treated with anabolic/androgenic steroids display increased offensive aggression and decreased anxiety correlated with an increase in vasopressin afferent development, synthesis, and neural signaling within the anterior hypothalamus. Upon withdrawal from anabolic/androgenic steroids, this neurobehavioral relationship shifts as hamsters display decreased offensive aggression and increased anxiety correlated with a decrease in anterior hypothalamic vasopressin. This study investigated the hypothesis that alterations in anterior hypothalamic vasopressin neural signaling modulate behavioral shifting between adolescent anabolic/androgenic steroid-induced offensive aggression and anxiety. To test this, adolescent male hamsters were administered anabolic/androgenic steroids and tested for offensive aggression or anxiety following direct pharmacological manipulation of vasopressin V1A receptor signaling within the anterior hypothalamus. Blockade of anterior hypothalamic vasopressin V1A receptor signaling suppressed offensive aggression and enhanced general and social anxiety in hamsters administered anabolic/androgenic steroids during adolescence, effectively reversing the pattern of behavioral response pattern normally observed during the adolescent exposure period. Conversely, activation of anterior hypothalamic vasopressin V1A receptor signaling enhanced offensive aggression in hamsters exposed to anabolic/androgenic steroids during adolescence. Together, these findings suggest that the state of vasopressin neural development and signaling in the anterior hypothalamus plays an important role in behavioral shifting between aggression and anxiety following adolescent exposure to anabolic/androgenic steroids. Copyright © 2016 Elsevier Inc. All rights reserved.

Is FDG PET/CT cost-effective for pre-operation staging of potentially operative non-small cell lung cancer? - From Chinese healthcare system perspective.

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Wang, Yu-ting; Huang, Gang

2012-08-01

The remarkable morbidity and mortality of lung cancer in the large population address major economic challenges to Chinese healthcare system. This study aims to assess the cost-effectiveness of fluorodeoxyglucose positron emission tomography (FDG PET)/CT for staging patients with non-small cell lung cancer (NSCLC) in China. Management of potentially operative NSCLC was modeled on decision analysis employing data in China. The strategies compared were conventional CT staging (strategy A), additional PET/CT in all patients (strategy B) or only in patients with normal-sized lymph nodes on CT (strategy C). Published medical data for Chinese patients was extracted. The costs corresponded to reimbursement by Chinese public health provider in 2010. Uncertainly of employed parameters was calculated in sensitivity analysis. Taking strategy A as baseline, the incremental cost-effectiveness ratio (ICER) of strategy B was 23,800RMB ($3500) per life year saved, which was acceptable in views of a developing country as China; while strategy C exhibited some loss of life years. Sensitivity analysis suggested the ICER (B-A) was raised more remarkably by a deterioration of PET specificity than by that of its sensitivity. The ICER was turned negative by PET specificity lower than 0.79. Economically, PET cost was proportional to the ICER (B-A), and decrease of palliative therapy cost could reduce both the ICER and overall cost. The PET/CT strategy is potentially cost-effective for management of NSCLC in China. Patients with nodal-positive CT results are not suggested to be excluded from further PET/CT. Furthermore, maintaining high specificity of PET in clinical scenarios is crucial. Prospective trials are warranted to transfer these results into policy making. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Modeling the dual pacemaker system of the tau mutant hamster.

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Oda, G A; Menaker, M; Friesen, W O

2000-06-01

Circadian pacemakers in many animals are compound. In rodents, a two-oscillator model of the pacemaker composed of an evening (E) and a morning (M) oscillator has been proposed based on the phenomenon of "splitting" and bimodal activity peaks. The authors describe computer simulations of the pacemaker in tau mutant hamsters viewed as a system of mutually coupled E and M oscillators. These mutant animals exhibit normal type 1 PRCs when released into DD but make a transition to a type 0 PRC when held for many weeks in DD. The two-oscillator model describes particularly well some recent behavioral experiments on these hamsters. The authors sought to determine the relationships between oscillator amplitude, period, PRC, and activity duration through computer simulations. Two complementary approaches proved useful for analyzing weakly coupled oscillator systems. The authors adopted a "distinct oscillators" view when considering the component E and M oscillators and a "system" view when considering the system as a whole. For strongly coupled systems, only the system view is appropriate. The simulations lead the authors to two primary conjectures: (1) the total amplitude of the pacemaker system in tau mutant hamsters is less than in the wild-type animals, and (2) the coupling between the unit E and M oscillators is weakened during continuous exposure of hamsters to DD. As coupling strength decreases, activity duration (alpha) increases due to a greater phase difference between E and M. At the same time, the total amplitude of the system decreases, causing an increase in observable PRC amplitudes. Reduced coupling also increases the relative autonomy of the unit oscillators. The relatively autonomous phase shifts of E and M oscillators can account for both immediate compression and expansion of activity bands in tau mutant and wild-type hamsters subjected to light pulses.

Protein A affinity chromatography of Chinese hamster ovary (CHO) cell culture broths containing biopharmaceutical monoclonal antibody (mAb): Experiments and mechanistic transport, binding and equilibrium modeling.

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Grom, Matic; Kozorog, Mirijam; Caserman, Simon; Pohar, Andrej; Likozar, Blaž

2018-04-15

Protein A-based affinity chromatography is a highly-efficient separation method to capture, purify and isolate biosimilar monoclonal antibodies (mAb) - an important medical product of biopharmaceutical industrial manufacturing. It is considered the most expensive step in purification downstream operations; therefore, its performance optimization offers a great cost saving in the overall production expenditure. The biochemical mixture-separating specific interaction experiments with Chinese hamster ovary (CHO) cell culture harvest, containing glycosylated extracellular immunoglobulins (Ig), were made using five different state-of-the-art commercial resins. Packing breakthrough curves were recorded at an array of prolonged residence times. A mathematical simulation model was developed, applied and validated in combination with non-linear regression algorithms on bed effluent concentrations to determine the previously-unknown binding properties of stationary phase materials. Apart from the columns' differential partitioning, the whole external system was also integrated. It was confirmed that internal pore diffusion is the global rate-limiting resistance of the compound retention process. Immobilizing substrate characteristics, obtained in this engineering study, are indispensable for the scale-up of the periodic counter-current control with mechanistic load, elution and wash reduction. Furthermore, unit's volumetric flow screening measurements revealed dynamic effect correlation to eluate quality parameters, like the presence of aggregates, the host cell-related impurities at supernatant's extended feeding, and titre. Numerical sensitivity outputs demonstrated the impacts of fluidics (e.g. axial dispersion coefficient), thermodynamics (Langmuir adsorption) and mass transfer fluxes. Copyright © 2018 Elsevier B.V. All rights reserved.

Molecular cloning and sequence analysis of hamster CENP-A cDNA

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Valdivia Manuel M

2002-05-01

Full Text Available Abstract Background The centromere is a specialized locus that mediates chromosome movement during mitosis and meiosis. This chromosomal domain comprises a uniquely packaged form of heterochromatin that acts as a nucleus for the assembly of the kinetochore a trilaminar proteinaceous structure on the surface of each chromatid at the primary constriction. Kinetochores mediate interactions with the spindle fibers of the mitotic apparatus. Centromere protein A (CENP-A is a histone H3-like protein specifically located to the inner plate of kinetochore at active centromeres. CENP-A works as a component of specialized nucleosomes at centromeres bound to arrays of repeat satellite DNA. Results We have cloned the hamster homologue of human and mouse CENP-A. The cDNA isolated was found to contain an open reading frame encoding a polypeptide consisting of 129 amino acid residues with a C-terminal histone fold domain highly homologous to those of CENP-A and H3 sequences previously released. However, significant sequence divergence was found at the N-terminal region of hamster CENP-A that is five and eleven residues shorter than those of mouse and human respectively. Further, a human serine 7 residue, a target site for Aurora B kinase phosphorylation involved in the mechanism of cytokinesis, was not found in the hamster protein. A human autoepitope at the N-terminal region of CENP-A described in autoinmune diseases is not conserved in the hamster protein. Conclusions We have cloned the hamster cDNA for the centromeric protein CENP-A. Significant differences on protein sequence were found at the N-terminal tail of hamster CENP-A in comparison with that of human and mouse. Our results show a high degree of evolutionary divergence of kinetochore CENP-A proteins in mammals. This is related to the high diverse nucleotide repeat sequences found at the centromere DNA among species and support a current centromere model for kinetochore function and structural

Genetic Association of Curative and Adverse Reactions to Tyrosine Kinase Inhibitors in Chinese advanced Non-Small Cell Lung Cancer patients

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Ruan, Yunfeng; Jiang, Jie; Guo, Liang; Li, Yan; Huang, Hailiang; Shen, Lu; Luan, Mengqi; Li, Mo; Du, Huihui; Ma, Cheng; He, Lin; Zhang, Xiaoqing; Qin, Shengying

2016-01-01

Epidermal growth factor receptor (EGFR) Tyrosine kinase inhibitor (TKI) is an effective targeted therapy for advanced non-small cell lung cancer (NSCLC) but also causes adverse drug reactions (ADRs) e.g., skin rash and diarrhea. SNPs in the EGFR signal pathway, drug metabolism/ transport pathways and miRNA might contribute to the interpersonal difference in ADRs but biomarkers for therapeutic responses and ADRs to TKIs in Chinese population are yet to be fully investigated. We recruited 226 Chinese advanced NSCLC patients who received TKIs erlotinib, gefitinib and icotinib hydrochloride and systematically studied the genetic factors associated with therapeutic responses and ADRs. Rs884225 (T > C) in EGFR 3′ UTR was significantly associated with lower risk of ADRs to erlotinib (p value = 0.0010, adjusted p value = 0.042). A multivariant interaction four-SNP model (rs884225 in EGFR 3′UTR, rs7787082 in ABCB1 intron, rs38845 in MET intron and rs3803300 in AKT1 5′UTR) was associated with ADRs in general and the more specific drug induced skin injury. The SNPs associated with both therapeutic responses and ADRs indicates they might share a common genetic basis. Our study provided potential biomarkers and clues for further research of biomarkers for therapeutic responses and ADRs in Chinese NSCLC patients. PMID:26988277

Household ventilation may reduce effects of indoor air pollutants for prevention of lung cancer: a case-control study in a Chinese population.

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Zi-Yi Jin

Full Text Available Although the International Agency for Research on Cancer (IARC has classified various indoor air pollutants as carcinogenic to humans, few studies evaluated the role of household ventilation in reducing the impact of indoor air pollutants on lung cancer risk.To explore the association between household ventilation and lung cancer.A population-based case-control study was conducted in a Chinese population from 2003 to 2010. Epidemiologic and household ventilation data were collected using a standardized questionnaire. Unconditional logistic regression was employed to estimate adjusted odds ratios (ORadj and their 95% confidence intervals (CI.Among 1,424 lung cancer cases and 4,543 healthy controls, inverse associations were observed for good ventilation in the kitchen (ORadj = 0.86, 95% CI: 0.75, 0.98, bedroom (ORadj = 0.90, 95% CI: 0.79, 1.03, and both kitchen and bedroom (ORadj = 0.87, 95% CI: 0.75, 1.00. Stratified analyses showed lung cancer inversely associated with good ventilation among active smokers (ORadj = 0.85, 95% CI: 0.72, 1.00, secondhand smokers at home (ORadj = 0.77, 95% CI: 0.63, 0.94, and those exposed to high-temperature cooking oil fumes (ORadj = 0.82, 95% CI: 0.68, 0.99. Additive interactions were found between household ventilation and secondhand smoke at home as well as number of household pollutant sources.A protective association was observed between good ventilation of households and lung cancer, most likely through the reduction of exposure to indoor air pollutants, indicating ventilation may serve as one of the preventive measures for lung cancer, in addition to tobacco cessation.

Household ventilation may reduce effects of indoor air pollutants for prevention of lung cancer: a case-control study in a Chinese population.

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Jin, Zi-Yi; Wu, Ming; Han, Ren-Qiang; Zhang, Xiao-Feng; Wang, Xu-Shan; Liu, Ai-Ming; Zhou, Jin-Yi; Lu, Qing-Yi; Kim, Claire H; Mu, Lina; Zhang, Zuo-Feng; Zhao, Jin-Kou

2014-01-01

Although the International Agency for Research on Cancer (IARC) has classified various indoor air pollutants as carcinogenic to humans, few studies evaluated the role of household ventilation in reducing the impact of indoor air pollutants on lung cancer risk. To explore the association between household ventilation and lung cancer. A population-based case-control study was conducted in a Chinese population from 2003 to 2010. Epidemiologic and household ventilation data were collected using a standardized questionnaire. Unconditional logistic regression was employed to estimate adjusted odds ratios (ORadj) and their 95% confidence intervals (CI). Among 1,424 lung cancer cases and 4,543 healthy controls, inverse associations were observed for good ventilation in the kitchen (ORadj = 0.86, 95% CI: 0.75, 0.98), bedroom (ORadj = 0.90, 95% CI: 0.79, 1.03), and both kitchen and bedroom (ORadj = 0.87, 95% CI: 0.75, 1.00). Stratified analyses showed lung cancer inversely associated with good ventilation among active smokers (ORadj = 0.85, 95% CI: 0.72, 1.00), secondhand smokers at home (ORadj = 0.77, 95% CI: 0.63, 0.94), and those exposed to high-temperature cooking oil fumes (ORadj = 0.82, 95% CI: 0.68, 0.99). Additive interactions were found between household ventilation and secondhand smoke at home as well as number of household pollutant sources. A protective association was observed between good ventilation of households and lung cancer, most likely through the reduction of exposure to indoor air pollutants, indicating ventilation may serve as one of the preventive measures for lung cancer, in addition to tobacco cessation.

Household Ventilation May Reduce Effects of Indoor Air Pollutants for Prevention of Lung Cancer: A Case-Control Study in a Chinese Population

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Han, Ren-Qiang; Zhang, Xiao-Feng; Wang, Xu-Shan; Liu, Ai-Ming; Zhou, Jin-Yi; Lu, Qing-Yi; Kim, Claire H.; Mu, Lina; Zhang, Zuo-Feng; Zhao, Jin-Kou

2014-01-01

Background Although the International Agency for Research on Cancer (IARC) has classified various indoor air pollutants as carcinogenic to humans, few studies evaluated the role of household ventilation in reducing the impact of indoor air pollutants on lung cancer risk. Objectives To explore the association between household ventilation and lung cancer. Methods A population-based case-control study was conducted in a Chinese population from 2003 to 2010. Epidemiologic and household ventilation data were collected using a standardized questionnaire. Unconditional logistic regression was employed to estimate adjusted odds ratios (ORadj) and their 95% confidence intervals (CI). Results Among 1,424 lung cancer cases and 4,543 healthy controls, inverse associations were observed for good ventilation in the kitchen (ORadj = 0.86, 95% CI: 0.75, 0.98), bedroom (ORadj = 0.90, 95% CI: 0.79, 1.03), and both kitchen and bedroom (ORadj = 0.87, 95% CI: 0.75, 1.00). Stratified analyses showed lung cancer inversely associated with good ventilation among active smokers (ORadj = 0.85, 95% CI: 0.72, 1.00), secondhand smokers at home (ORadj = 0.77, 95% CI: 0.63, 0.94), and those exposed to high-temperature cooking oil fumes (ORadj = 0.82, 95% CI: 0.68, 0.99). Additive interactions were found between household ventilation and secondhand smoke at home as well as number of household pollutant sources. Conclusions A protective association was observed between good ventilation of households and lung cancer, most likely through the reduction of exposure to indoor air pollutants, indicating ventilation may serve as one of the preventive measures for lung cancer, in addition to tobacco cessation. PMID:25019554

Metabolism of tributyltin and triphenyltin by rat, hamster and human hepatic microsomes

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Ohhira, Shuji; Watanabe, Masatomo; Matsui, Hisao [Department of Hygiene, Dokkyo University School of Medicine, Mibu-machi, 321-0293, Tochigi (Japan)

2003-03-01

Tributyltin and triphenyltin are metabolized by cytochrome P-450 system enzymes, and their metabolic fate may contribute to the toxicity of the chemicals. In the current study, the in vitro metabolism of tributyltin and triphenyltin by rat, hamster and human hepatic microsomes was investigated to elucidate the metabolic competence for these compounds in humans. The metabolic reaction using microsome-NADPH system that is usually conducted was not applicable to in vitro metabolism of organotins, especially triphenyltin. We therefore examined the effects of dithiothreitol (DTT), one of the antioxidants for sulfhydryl groups, to determine the in vitro metabolism of tributyltin and triphenyltin. As a result, the treatment with 0.1 mM DTT in vitro increased the activity of the microsomal monooxygenase system for metabolism of tributyltin as well as triphenyltin; the total yield of tributyltin and triphenyltin metabolites as tin increased, respectively, by approximately 1.8 and 8.9 times for rat, 2.1 and 1.2 times for hamster, and 1.6 and 1.5 times for human. It is suggested that the organotins directly inactivate cytochrome P-450 because of the interaction with critical sulfhydryl groups of the hemoprotein. We confirmed the utility of this in vitro metabolic system using DTT in the hepatic microsomes of phenobarbital (PB)-pretreated and untreated hamsters. Thus, the in vitro metabolic system described here was applied to a comparative study of the metabolism of organotins in rats, hamsters and humans. Tributyltin was metabolized more readily than triphenyltin in all the species. In humans, the in vitro metabolic pattern resembled that of hamsters, which were susceptible to in vivo triphenyltin toxicity because of incompetent metabolism. It is possible that the hamster is a qualitatively and quantitatively suitable animal model for exploring the influence of tributyltin and triphenyltin in humans. (orig.)

Antiviral Activity of Favipiravir (T-705) against a Broad Range of Paramyxoviruses In Vitro and against Human Metapneumovirus in Hamsters.

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Jochmans, D; van Nieuwkoop, S; Smits, S L; Neyts, J; Fouchier, R A M; van den Hoogen, B G

2016-08-01

The clinical impact of infections with respiratory viruses belonging to the family Paramyxoviridae argues for the development of antiviral therapies with broad-spectrum activity. Favipiravir (T-705) has demonstrated potent antiviral activity against multiple RNA virus families and is presently in clinical evaluation for the treatment of influenza. Here we demonstrate in vitro activity of T-705 against the paramyxoviruses human metapneumovirus (HMPV), respiratory syncytial virus, human parainfluenza virus, measles virus, Newcastle disease virus, and avian metapneumovirus. In addition, we demonstrate activity against HMPV in hamsters. T-705 treatment inhibited replication of all paramyxoviruses tested in vitro, with 90% effective concentration (EC90) values of 8 to 40 μM. Treatment of HMPV-challenged hamsters with T-705 at 200 mg/kg of body weight/day resulted in 100% protection from infection of the lungs. In all treated and challenged animals, viral RNA remained detectable in the respiratory tract. The observation that T-705 treatment had a significant effect on infectious viral titers, with a limited effect on viral genome titers, is in agreement with its proposed mode of action of viral mutagenesis. However, next-generation sequencing of viral genomes isolated from treated and challenged hamsters did not reveal (hyper)mutation. Polymerase activity assays revealed a specific effect of T-705 on the activity of the HMPV polymerase. With the reported antiviral activity of T-705 against a broad range of RNA virus families, this small molecule is a promising broad-range antiviral drug candidate for limiting the viral burden of paramyxoviruses and for evaluation for treatment of infections with (re)emerging viruses, such as the henipaviruses. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Propagation of Asian isolates of canine distemper virus (CDV in hamster cell lines

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Yamaguchi Ryoji

2009-10-01

Full Text Available Abstract Backgrounds The aim of this study was to confirm the propagation of various canine distemper viruses (CDV in hamster cell lines of HmLu and BHK, since only a little is known about the possibility of propagation of CDV in rodent cells irrespective of their epidemiological importance. Methods The growth of CDV in hamster cell lines was monitored by titration using Vero.dogSLAMtag (Vero-DST cells that had been proven to be susceptible to almost all field isolates of CDV, with the preparations of cell-free and cell-associated virus from the cultures infected with recent Asian isolates of CDV (13 strains and by observing the development of cytopathic effect (CPE in infected cultures of hamster cell lines. Results Eleven of 13 strains grew in HmLu cells, and 12 of 13 strains grew in BHK cells with apparent CPE of cell fusion in the late stage of infection. Two strains and a strain of Asia 1 group could not grow in HmLu cells and BHK cells, respectively. Conclusion The present study demonstrates at the first time that hamster cell lines can propagate the majority of Asian field isolates of CDV. The usage of two hamster cell lines suggested to be useful to characterize the field isolates biologically.

Polymorphisms in GEMIN4 and AGO1 Genes Are Associated with the Risk of Lung Cancer: A Case-Control Study in Chinese Female Non-Smokers

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Xue Fang

2016-09-01

Full Text Available MicroRNA biosynthesis genes can affect the regulatory effect of global microRNAs to target mRNA and hence influence the genesis and development of human cancer. Here, we selected five single nucleotide polymorphisms (SNPs (rs7813, rs2740349, rs2291778, rs910924, rs595961 in two key microRNA biosynthesis genes (GEMIN4 and AGO1 and systematically evaluated the association between these SNPs, the gene-environment interaction and lung cancer risk. To control the impact of cigarette smoking on lung cancer, we recruited Chinese female non-smokers for the study. The total number of lung cancer cases and cancer-free controls were 473 and 395 in the case-control study. Four SNPs showed statistically significant associations with lung cancer risk. After Bonferroni correction, rs7813 and rs595961 were evidently still associated with lung cancer risk. In the stratified analysis, our results revealed that all five SNPs were associated with the risk of lung adenocarcinoma; after Bonferroni correction, significant association was maintained for rs7813, rs910924 and rs595961. Haplotype analysis showed GEMIN4 haplotype C-A-G-T was a protective haplotype for lung cancer. In the combined unfavorable genotype analysis, with the increasing number of unfavorable genotypes, a progressively increased gene-dose effect was observed in lung adenocarcinoma. We also found that individuals exposed to cooking oil fumes showed a relatively high risk of lung cancer, but no interactions were found between cooking oil fume exposure or passive smoking exposure with these SNPs, either on an additive scale or a multiplicative scale. Overall, this is the first study showing that rs7813 and rs595961 could be meaningful as genetic markers for lung cancer risk.

Delay of behavioral estrus in hamsters and phenobarbital.

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Alleva, J J

1989-01-01

The onset of behavioral estrus was used as a phase marker of the hamster timing system in SLD 16:8 (dark 20:00-04:00). TZ was injected between 11:00 of cycle day 3 and noon of cycle day 4 when onset of estrus was determined. At no time did injection of TZ cause a phase advance in SLD 16:8. Small delays of estrus resulted from 11:00-16:00 injections but marked delays began with the 17:00 injection. Phenobarbital was injected between noon and 19:30 on cycle day 3. Injections between noon and 16:00 had no effect but all later injections beginning at 17:00 delayed estrus, the 17:30 injection causing the greatest delay. Diazepam also markedly delayed estrus when tested at 17:30. These results with three drugs support results with light pulses that 18:00 in SLD 16:8 marks the same phase of the 24-h hamster timing system as the onset of wheel running does in DD, LL, and WLD. These findings with three GABA potentiators extend to SLD previous evidence based on the onset of wheel running in DD, LL and WLD that GABA may be involved in hamster timekeeping and its responses to light and drugs.

Potential Combinational Anti-Cancer Therapy in Non-Small Cell Lung Cancer with Traditional Chinese Medicine Sun-Bai-Pi Extract and Cisplatin

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Wang, Jhih-Syuan; Chung, Meng-Chi; Chang, Jing-Fen; Chao, Ming-Wei

2016-01-01

Traditional lung cancer treatments involve chemical or radiation therapies after surgical tumor removal; however, these procedures often kill normal cells as well. Recent studies indicate that chemotherapies, when combined with Traditional Chinese Medicines, may offer a new way to treat cancer. In vitro tests measuring the induction of autophagy and/or apoptosis were used to examine the cytotoxicity of SBPE, commonly used for lung inflammation on A549 cell line. The results indicated that intercellular levels of p62 and Atg12 were increased, LC3-I was cleaved into LC3-II, and autophagy was induced with SBPE only. After 24 hours, the apoptotic mechanism was induced. If the Cisplatin was added after cells reached the autophagy state, we observed synergistic effects of the two could achieve sufficient death of lung cancer cells. Therefore, the Cisplatin dosage used to induce apoptosis could be reduced by half, and the amount of time needed to achieve the inhibitory concentration of 50% was also half that of the original. In addition to inducing autophagy within a shortened period of time, the SBPE and chemotherapy drug combination therapy was able to achieve the objective of rapid low-dosage cancer cell elimination. Besides, SBPE was applied with Gemcitabine or Paclitaxel, and found that the combination treatment indeed achieve improved lung cancer cell killing effects. However, SBPE may also be less toxic to normal cells. PMID:27171432

Differential effect of lithium on the circadian oscillator in young and old hamsters

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Iwahana, Eiko; Hamada, Toshiyuki; Uchida, Ayumi; Shibata, Shigenobu

2007-01-01

Lithium is one of the most commonly used drugs in the prophylaxis and treatment of bipolar disorder. It is also known to lengthen circadian period in several organisms. Previously, we reported that there was the association between lengthening circadian period by lithium and GSK-3 protein and its enzyme activity in the mouse suprachiasmatic nucleus (SCN). In this study, we show that lithium affects the circadian oscillator in young and old hamster SCN, in an age-dependent manner. We found that basal levels of phosphorylated GSK-3 (pGSK-3) protein expression in old hamsters are much lower than that in young hamsters. Furthermore, in the old hamsters, lithium did not affect the period of the locomotor activity rhythm or pGSK-3 expression, while changing period and pGSK-3 in the younger animals. These results indicate that the content of pGSK-3 in the SCN has an important role in age-dependent effects of lithium on the circadian oscillator

SPECT/CT of lung nodules using 111In-DOTA-c(RGDfK) in a mouse lung carcinogenesis model.

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Hayakawa, Takuya; Mutoh, Michihiro; Imai, Toshio; Tsuta, Koji; Yanaka, Akinori; Fujii, Hirofumi; Yoshimoto, Mitsuyoshi

2013-08-01

Lung cancer is one of the leading causes of cancer-related deaths worldwide, including Japan. Although computed tomography (CT) can detect small lung lesions such as those appearing as ground glass opacity, it cannot differentiate between malignant and non-malignant lesions. Previously, we have shown that single photon emission computed tomography (SPECT) imaging using (111)In-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid-cyclo-(Arg-Gly-Asp-D-Phe-Lys) (DOTA-c(RGDfK)), an imaging probe of αvβ3 integrin, is useful for the early detection of pancreatic cancer in a hamster pancreatic carcinogenesis model. In this study, we aimed to assess the usefulness of SPECT/CT with (111)In-DOTA-c(RGDfK) for the evaluation of the malignancy of lung cancer. Lung tumors were induced by a single intraperitoneal injection (250 mg/kg) of urethane in male A/J mice. Twenty-six weeks after the urethane treatment, SPECT was performed an hour after injection of (111)In-DOTA-c(RGDfK). Following this, the radioactivity ratios of tumor to normal lung tissue were measured by autoradiography (ARG) in the excised lung samples. We also examined the expression of αvβ3 integrin in mouse and human lung samples. Urethane treatment induced 5 hyperplasias, 41 adenomas and 12 adenocarcinomas in the lungs of 8 A/J mice. SPECT with (111)In-DOTA-c(RGDfK) could clearly visualize lung nodules, though we failed to detect small lung nodules like adenoma and hyperplasias (adenocarcinoma: 66.7%, adenoma: 33.6%, hyperplasia: 0.0%). ARG analysis revealed significant uptake of (111)In-DOTA-c(RGDfK) in all the lesions. Moreover, tumor to normal lung tissue ratios increased along with the progression of carcinogenesis. Histopathological examination using human lung tissue samples revealed clear up-regulation of αvβ3 integrin in well-differentiated adenocarcinoma (Noguchi type B and C) rather than atypical adenomatous hyperplasia. Although there are some limitations in evaluating the malignancy of

After infection with Leishmania infantum, Golden Hamsters (Mesocricetus auratus) become more attractive to female sand flies (Lutzomyia longipalpis).

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Nevatte, T M; Ward, R D; Sedda, L; Hamilton, J G C

2017-07-21

In Brazil, human and canine visceral leishmaniasis is caused by infection with Leishmania infantum, a Protist parasite transmitted by blood-feeding female Lutzomyia longipalpis sand flies. The objective of this study was to determine if the odour of hamsters, infected with Le. infantum, was more attractive than the odour of the same hamsters, before they were infected. The attractiveness of odour collected from individual hamsters (n = 13), before they were infected, was compared in a longitudinal study, with the attractiveness of the odour of the same hamster in a Y-tube olfactometer bioassay, at a late stage of infection. The odour of six of the golden hamsters was significantly more attractive to 50% of the female sand flies at the end of infection compared to before infection and the odour of four of the golden hamsters was significantly more attractive to 75% of the female sand flies at the end of infection. These results strongly indicate that hamsters infected with Le. infantum become significantly more attractive to a greater proportion of female sand flies as the infection progresses.

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

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Murai, T; Kuwabara, M; Sato, F; Kubo, K; Itoh, T; Yoshii, G

1985-06-01

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/sup +/) cells as well as thymidine kinase deficient (TK/sup -/) 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/sup +/ cells, both 2'-Cl-TdR and TdR enhanced the killing efficiency of X-rays and ultraviolet light. On the other hand, in the TK/sup -/ 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).

Tetrathyridia of Mesocestoides lineatus in Chinese Snakes and Their Adults Recovered from Experimental Animals

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Cho, Shin-Hyeong; Kim, Tong-Soo; Kong, Yoon; Na, Byoung-Kuk

2013-01-01

Morphological characteristics of Mesocestoides lineatus tetrathyridia collected from Chinese snakes and their adults recovered from experimental animals were studied. The tetrathyridia were detected mainly in the mesentery of 2 snake species, Agkistrodon saxatilis (25%) and Elaphe schrenckii (20%). They were 1.73 by 1.02 mm in average size and had an invaginated scolex with 4 suckers. Adult tapeworms were recovered from 2 hamsters and 1 dog, which were orally infected with 5-10 larvae each. Adults from hamsters were about 32 cm long and those from a dog were about 58 cm long. The scolex was 0.56 mm in average width with 4 suckers of 0.17 by 0.15 mm in average size. Mature proglottids measured 0.29 by 0.91 mm (av.). Ovaries and vitellaria bilobed and located in the posterior portion of proglottids. The cirrus sac was oval-shaped and located median. Testes were follicular, distributed in both lateral fields of proglottids, and 41-52 in number per proglottid. Gravid proglottids were 1.84 by 1.39 mm (av.) with a characteristic paruterine organ. Eggs were 35 by 27 µm in average size with a hexacanth embryo. These morphological characteristics of adult worms were identical with those of M. lineatus reported previously. Therefore, it has been confirmed that the tetrathyridia detected in 2 species of Chinese snakes are the metacestodes of M. lineatus, and 2 snake species, A. saxatilis and E. schrenckii, play the role of intermediate hosts. PMID:24327778

Effect of deuterium on the circadian period and metabolism in wild-type and tau mutant Syrian hamsters

NARCIS (Netherlands)

Oklejewicz, M; Hut, RA; Daan, S

2000-01-01

Homozygous tau mutant Syrian hamsters (tau-/-) have a free-running circadian period (tau) around 20 h and a proportionally higher metabolic rate compared with wild-type hamsters (tau+/+) with a period of circa 24 h. In this study, we applied deuterium oxide (D2O) to hamsters to test whether

Experimental treatment with sodium stibogluconate of hamsters infected with Leishmania (Leishmania) chagasi and Leishmania (Leishmania) amazonensis Tratamento experimental com stibogluconato de sódio em hamsters infectados com Leishmania (Leishmania) chagasi e Leishmania (Leishmania) amazonensis

OpenAIRE

Elizabeth M. de Figueiredo; Jaime Costa e Silva; Reginaldo P. Brazil

1999-01-01

The present paper reports the experimental treatment of hamsters infected with Leishmania chagasi and Leishmania amazonensis with sodium stibogluconate (20mg/kg/day x 20 days). Only with L. chagasi did the treatment result in the complete elimination of parasites from the spleen. However, no parasitological cure was achieved in hamsters infected with L. amazonensis.O presente trabalho é um relato do tratamento experimental de hamsters infectado com Leishmania chagasi e Leishmania amazonensis ...

Rates of incorporation of radioactive molecules during the cell cycle

International Nuclear Information System (INIS)

Gray, J.W.; Pallavicini, M.G.; George, Y.S.; Groppi, V.; Look, M.; Dean, P.N.

1981-01-01

We report measurements of the incorporation of radioactive molecules during short labeling periods, as a function of cell-cycle stage, using a cell-sorter-based technique that does not require cell synchronization. We have determined: (1) tritiated thymidine ( 3 H-TdR) incorporation throughout S-phase in Lewis lung tumor cells in vitro both before and after treatment with cytosine arabinoside; (2) 3 H-TdR incorporation throughout S-phase in KHT tumor cells in vitro and in vivo; (3) 3 H-TdR incorporation throughout S-phase in Chinese hamster ovary cells and compared it with DNA synthesis throughout S-phase; (4) a mathematical expression describing 3 H-TdR incorporation throughout S-phase in Chinese hamster M3-1 cells; and (5) the simultaneous incorporation of 3 H-TdR and 35 S-methionine as they are related to cell size and DNA content in S49 mouse lymphoma cells. In asynchronously growing cells in vitro and in vivo, 3 H-TdR incorporation was generally low in early and late S-phase and highest in mid-S-phase. However, in Lewis lung tumor cells treated with cytosine arabinoside 3 H-TdR incorporation was highest in early and late S-phase and lowest in mid-S-phase. Incorporation of 35 S-methionine increased continuously with cell size and DNA content. Incorporation of 3 H-TdR in CHO cells was proportional to DNA synthesis

Caffeine enhancement of x-ray killing in cultured human and rodent cells

International Nuclear Information System (INIS)

Waldren, C.A.; Rasko, I.

1978-01-01

A 16 to 20 hr postirradiation incubation with caffeine enhances x-ray killing of rodent and human cells. Cells tested were Chinese hamster ovary (CHO-K1), lung (CHL), V79, mouse L, HeLa S3, human fibroblasts (AF288, TC171, FS9, CRL1166), and a human-hamster hybrid. The effect of caffeine on the x-ray survival curve of these cells was to remove the initial shoulder without significantly altering the mean lethal dose (D 0 ). This action can be achieved at caffeine concentrations which of themselves cause less than 15% killing. In randomly growing CHO-K1 cells the caffeine-sensitive process occurs with a half-time of 2 to 5 hr after irradiation. These experiments indicate the existence in human and rodent cells of caffeine-inhibited genome repair for x-ray damage

The accumulation of 134Cs in heart and skeletal muscle of healthy and dystrophic hamsters

International Nuclear Information System (INIS)

Szentkuti, L.; Breitrueck, H.; Giese, W.

1976-01-01

he accumulation of cesium-134 in heart and skeletal muscle of healthy and dystrophic hamsters was compared. It was lower in dystrophic hamsters than in normal ones after only a single dose of cesium-134. The 134 Cs-concentrations of heart and 'red' skeletal muscle were different between normal and dystrophic hamsters. When the isotope had equilibrated in the animals differences in 134 Cs-accumulation in muscle tissue between normal and dystrophic hamsters were even more obvious. The faster elimination of cesium-134 from the body as affected by muscular dystrophy was due to a reduction of 134 Cs-accumulation in muscle tissue. The reduced ability of damaged muscles to accumulate Cs-ions offers the possibility to use Cs-isotopes in diagnosis of skeletal muscle dystrophy. (author)

Treating advanced non-small-cell lung cancer in Chinese patients: focus on icotinib

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Liang JL

2014-05-01

Full Text Available Jun-Li Liang,1 Xiao-Cang Ren,2 Qiang Lin2 1Department of Radiation Oncology, Hebei Medical University Fourth Hospital, Shijiazhuang, People’s Republic of China; 2Department of Oncology, North China Petroleum Bureau General Hospital of Hebei Medical University, Renqiu, Hebei Province, People’s Republic of China Abstract: Icotinib hydrochloride is an orally administered small-molecule reversible tyrosine kinase inhibitor that has been independently researched and developed and has independent intellectual property rights in the People’s Republic of China. Clinical trials have demonstrated that the response to icotinib among advanced non-small-cell lung cancer (NSCLC patients who received at least one platinum-based chemotherapy regimen was not inferior to gefitinib. Since being launched August 2011 in the People’s Republic of China, icotinib has been widely used in clinics, and has become an important treatment option for Chinese patients with advanced NSCLC. The present study presents the Phase I, II, and III clinical trials of icotinib and discusses current clinical applications in the People’s Republic of China and future research directions. Keywords: targeted therapy, EGFR-TKI, NSCLC

Toxicity of inhaled 144CeO2 in immature, young adult and aged Syrian hamsters. II

International Nuclear Information System (INIS)

Hobbs, C.H.; McClellan, R.O.; Benjamin, S.A.

1974-01-01

Syrian hamsters have been exposed to aerosols of 144 CeO 2 at 28 (immature), 84 (young adult), and 340 (aged) days of age to better define the dose-response relationships following inhalation of this radionuclide by a population with a wide range of ages such as would be the case with a human population following a catastrophic nuclear accident. The animals were exposed to achieve graded initial lung burdens (ILB) for the younger exposure ages of about 20, 5, 1.25, 0.31, 0.80, and 0.01 μCi and control groups exposed to stable cerium oxide. The aged animals were exposed to achieve ILB of 20, 5, 1.25, and 0.31 μCi as well as a control group. Animals are being maintained both for serial sacrifice to determine the radiation dose pattern and for lifespan observation to determine dose-response relationships. The effective half-life of 144 Ce in the lung appears to be about 63 days. This would result in a dose to lung of about 4000 rads/μCi of ILB. Animals with ILB of about 20 μCi have died at early times with radiation pneumonitis and pulmonary fibrosis. No excessive mortality compared to that of controls has been observed in the remaining exposure levels. Histopathologic examination is not complete on all animals that have died, but no pulmonary neoplasms have been observed to date. (U.S.)

X-ray induced dominant lethal mutations in mature and immature oocytes of guinea-pigs and golden hamsters

International Nuclear Information System (INIS)

Cox, B.D.; Lyon, M.F.

1975-01-01

The induction of dominant lethal mutations by doses of 100-400 rad X-rays in oocytes of the guinea-pig and golden hamster was studied using criteria of embryonic mortality. For both species higher yields were obtained from mature than from immature oocytes. Data on fertility indicated that in the golden hamster immature oocytes were more sensitive to killing by X-rays than mature oocytes but that the converse was true in the guinea-pig. The dose-response relationship for mutation to dominant lethals in pre-ovulatory oocytes of guinea-pigs and golden hamsters was linear, both when based on pre- and post-implantation loss only. The rate per unit dose was higher for the golden hamster, and the old golden hamsters were possibly slightly more sensitive than young ones

Identification of hamster inducible nitric oxide synthase (iNOS) promoter sequences that influence basal and inducible iNOS expression

Science.gov (United States)

Saldarriaga, Omar A.; Travi, Bruno L.; Choudhury, Goutam Ghosh; Melby, Peter C.

2012-01-01

IFN-γ/LPS-activated hamster (Mesocricetus auratus) macrophages express significantly less iNOS (NOS2) than activated mouse macrophages, which contributes to the hamster's susceptibility to intracellular pathogens. We determined a mechanism responsible for differences in iNOS promoter activity in hamsters and mice. The HtPP (1.2 kb) showed low basal and inducible promoter activity when compared with the mouse, and sequences within a 100-bp region (−233 to −133) of the mouse and hamster promoters influenced this activity. Moreover, within this 100 bp, we identified a smaller region (44 bp) in the mouse promoter, which recovered basal promoter activity when swapped into the hamster promoter. The mouse homolog (100-bp region) contained a cis-element for NF-IL-6 (−153/−142), which was absent in the hamster counterpart. EMSA and supershift assays revealed that the hamster sequence did not support the binding of NF-IL-6. Introduction of a functional NF-IL-6 binding sequence into the hamster promoter or its alteration in the mouse promoter revealed the critical importance of this transcription factor for full iNOS promoter activity. Furthermore, the binding of NF-IL-6 to the iNOS promoter (−153/−142) in vivo was increased in mouse cells but was reduced in hamster cells after IFN-γ/LPS stimulation. Differences in the activity of the iNOS promoters were evident in mouse and hamster cells, so they were not merely a result of species-specific differences in transcription factors. Thus, we have identified unique DNA sequences and a critical transcription factor, NF-IL-6, which contribute to the overall basal and inducible expression of hamster iNOS. PMID:22517919

Social housing and social isolation: Impact on stress indices and energy balance in male and female Syrian hamsters (Mesocricetus auratus).

Science.gov (United States)

Ross, Amy P; Norvelle, Alisa; Choi, Dennis C; Walton, James C; Albers, H Elliott; Huhman, Kim L

2017-08-01

Although Syrian hamsters are thought to be naturally solitary, recent evidence from our laboratory demonstrates that hamsters may actually prefer social contact. Hamsters increase their preference for a location associated with an agonistic encounter regardless of whether they have "won" or "lost". It has also been reported that social housing as well as exposure to intermittent social defeat or to a brief footshock stressor increase food intake and body mass in hamsters. By contrast, it has also been suggested that housing hamsters in social isolation causes anxiety-induced anorexia and reductions in body mass selectively in females. The purpose of this study was to determine the physiological consequences of housing hamsters in social isolation versus in social groups. Male and female hamsters were housed singly or in stable groups of 5 for 4weeks after which they were weighed and trunk blood was collected. In addition, fat pads and thymus and adrenal glands were extracted and weighed. Serum and fecal cortisol were measured using an enzyme-linked immunoassay. Housing condition had no effect on serum or fecal cortisol, but socially housed hamsters displayed modest thymus gland involution. Socially housed females weighed more than did any other group, and socially housed females and males had more fat than did socially isolated hamsters. No wounding or tissue damage occurred in grouped hamsters. Overall, these data suggest that Syrian hamsters tolerate both stable social housing and social isolation in the laboratory although social housing is associated with some alteration in stress-related and bioenergetic measures. Copyright © 2017 Elsevier Inc. All rights reserved.

Melatonin and schistosomal antigens ameliorate the anti-oxidative and biochemical response to Schistosoma mansoni infection in hamster

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Omema SALAH

2009-04-01

Full Text Available The present study was designed to investigate the potential protective effect of melatonin as an antioxidant separately or in combination with antigens (cercarial; CAP or soluble worm; SWAP against Schistosoma mansoni infection in hamsters. Each hamster was sensitized with an initial immunization of 0.6 ml of the extracted antigen (30 μg protein/mL. After four days, a second injection of 0.4 mL was given (20 μg protein/mL. Then, each hamster was exposed to 260 ± 20 S.mansoni cercariae followed with melatonin treatment (3.5 mg/kg for thirty days from the 1st day of post infection. Levels of lipid peroxidation (LPO products, catalase (CAT activity, hepatic glutathione (GSH and biochemical changes in the liver and kidneys functions were investigated. The results revealed a high significant increasing of LPO and decreasing of CAT and GSH in liver of infected hamsters. Biochemical observations showed severe damage in the liver enzyme activities and increasing cholesterol level in infected animals. Melatonin co-treatment with antigen to the infected-hamster attenuated the increase of LPO and restored the activity of CAT and levels of hepatic GSH. Also, the biochemical damages in the liver and kidneys functions were reduced. The present study suggests that melatonin may be useful in combating free radical-induced damage due to infection toxicity. The immunization with previous antigens resulted in a remarkable improvement on the liver enzyme activities, which were increased after infection. Thus, vaccination of hamsters with antigens (both CAP and SWAP and melatonin treatment has more potent effect on the enhancement of antioxidant and biochemical of S. mansoni infected-hamster than each treatment separately. Immunization of the hamster with SWAP followed by melatonin was the best way among the other regime treatments to improve the biochemical and antioxidant parameters of the infected-hamsters

Monosodium glutamate-induced arcuate nucleus damage affects both natural torpor and 2DG-induced torpor-like hypothermia in Siberian hamsters.

Science.gov (United States)

Pelz, Kimberly M; Routman, David; Driscoll, Joseph R; Kriegsfeld, Lance J; Dark, John

2008-01-01

Siberian hamsters (Phodopus sungorus) have the ability to express daily torpor and decrease their body temperature to approximately 15 degrees C, providing a significant savings in energy expenditure. Daily torpor in hamsters is cued by winterlike photoperiods and occurs coincident with the annual nadirs in body fat reserves and chronic leptin concentrations. To better understand the neural mechanisms underlying torpor, Siberian hamster pups were postnatally treated with saline or MSG to ablate arcuate nucleus neurons that likely possess leptin receptors. Body temperature was studied telemetrically in cold-acclimated (10 degrees C) male and female hamsters moved to a winterlike photoperiod (10:14-h light-dark cycle) (experiments 1 and 2) or that remained in a summerlike photoperiod (14:10-h light-dark cycle) (experiment 3). In experiment 1, even though other photoperiodic responses persisted, MSG-induced arcuate nucleus ablations prevented the photoperiod-dependent torpor observed in saline-treated Siberian hamsters. MSG-treated hamsters tended to possess greater fat reserves. To determine whether reductions in body fat would increase frequency of photoperiod-induced torpor after MSG treatment, hamsters underwent 2 wk of food restriction (70% of ad libitum) in experiment 2. Although food restriction did increase the frequency of torpor in both MSG- and saline-treated hamsters, it failed to normalize the proportion of MSG-treated hamsters undergoing photoperiod-dependent torpor. In experiment 3, postnatal MSG treatments reduced the proportion of hamsters entering 2DG-induced torpor-like hypothermia by approximately 50% compared with saline-treated hamsters (38 vs. 72%). In those MSG-treated hamsters that did become hypothermic, their minimum temperature during hypothermia was significantly greater than comparable saline-treated hamsters. We conclude that 1) arcuate nucleus mechanisms mediate photoperiod-induced torpor, 2) food-restriction-induced torpor may also be

Efficacy and safety of icotinib in Chinese patients with advanced non-small cell lung cancer after failure of chemotherapy.

Science.gov (United States)

Shao, Lan; Zhang, Beibei; He, Chunxiao; Lin, Baochai; Song, Zhengbo; Lou, Guangyuan; Yu, Xinmin; Zhang, Yiping

2014-01-01

The preclinical experiments and several clinical studies showed icotinib, an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, in Chinese patients with advanced non-small cell lung cancer (NSCLC) who failed previous chemotherapy. We performed a retrospective study of the efficacy and safety of icotinib monotherapy in a different and more recent sample of Chinese patients. The clinical data of 149 patients with advanced NSCLC who were admitted to Zhejiang Cancer Hospital from August 1, 2011 to July 31, 2012 were retrospectively analyzed. All patients were given icotinib treatment after the failure of previous chemotherapy. Univariate and multivariate analyses were conducted based on the Kaplan Meier method and Cox proportional hazards model. The objective response rate was 33/149 and disease control rate was 105/149. No complete response occurred. Median progression free survival (PFS) with icotinib treatment was 5.03 months (95% CI: 3.51 to 6.55). Median overall survival was 12.3 months (95% CI: 10.68 to 13.92). Multivariate analysis showed that the mutation of EGFR and one regimen of prior chemotherapy were significantly associated with longer PFS. At least one drug related adverse event was observed in 65.8% (98/149) of patients, but mostly grade 1 or 2 and reversible and none grade 4 toxicity. Icotinib monotherapy is an effective and well tolerated regimen for Chinese patients with NSCLC after the failure of chemotherapy. It is a promising agent and further study with icotinib in properly conducted trials with larger patient samples and other ethnic groups is warranted.

Steroid metabolism in pregnant hamster. I

International Nuclear Information System (INIS)

Marchut, M.

1980-01-01

Quartered placentae from 12- and 15-day pregnant hamsters were incubated with 14 C labelled pregnenolone and progesterone and the products of their conversion were identified by chromatographic and isotope dilution methods. Pregnenolone was converted to progesterone, 7α-hydroxypregnenolone, 7α-hydroxyprogesterone, 3α-hydroxy-5β-pregnan-20-one, 3β-hydroxy-5α-pregnan-20-one, 3α-hydroxy-5α-pregnan-20-one, 5β-pregnane-3,20-dione and 5α-pregnane-3,20-dione. Except for 7α-hydroxypregnenolone, the same metabolites were identified in the incubates of the placental tissue with progesterone. Thus, the activity of Δ 5 -3β-hydroxysteroid dehydrogenase and Δsup(5→4) isomerase, 7α-hydrΔ 4 -5β- and Δ 4 -5α-reductase enzyme systems was shown in the hamster placenta. The formation of androgens from pregnenolone, progesterone and their 17-hydroxy-derivatives was not observed. There was also no evidence of the formation of estrogens from the above C-21 steroid precursors. (author)

Effects of aqueous cinnamon extract on chemically-induced carcinoma of hamster cheek pouch mucosa

Directory of Open Access Journals (Sweden)

Samah K. Ezzat

2017-12-01

Full Text Available This study aimed to investigate the effects of aqueous cinnamon extract (ACE on 7, 12-Dimethylbenz[a]anthracene (DMBA-induced oral carcinogenesis in hamster cheek pouch (HCP mucosa. Sixty male Syrian hamsters were randomly divided into six equal groups. The hamsters of groups I, II and III received no treatment, DMBA and ACE respectively, for 16 weeks. Groups IV and V were handled as group II and concomitantly treated with ACE for the same period and additionally group V received ACE for other 16 weeks after the stoppage of DMBA application. Group VI hamsters were handled as group III and additionally received DMBA for other 16 weeks after the stoppage of ACE supplementation. Hamsters of each group were euthanized according to the experimental schedule. The buccal pouches were and prepared for H&E stain, PAS reagent, CD3 and PDGF immunohistochemical reactivity. All groups showed dysplastic changes with varying degrees except groups I and III. Deep invasive carcinomas were recorded in 90% of the samples of group II, 60% of group IV, 50% of group V and 40% of group VI. From the previous results, it can be concluded that ACE has the potentiality preventing oral cancer initiation better than inhibiting oral cancer progression.

The functional polymorphism of NBS1 p.Glu185Gln is associated with an increased risk of lung cancer in Chinese populations: Case–control and a meta-analysis

Energy Technology Data Exchange (ETDEWEB)

Fang, Wenxiang; Qiu, Fuman; Zhang, Lisha [The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis, Collaborative Innovation Center for Environmental Toxicity, Guangzhou Medical University, Guangzhou 510182 (China); Deng, Jieqiong [Soochow University Laboratory of Cancer Molecular Genetics, Collaborative Innovation Center for Environmental Toxicity, Medical College of Soochow University, Suzhou 215123 (China); Zhang, Haibo [Department of Cardio-thoracic Surgery, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510080 (China); Yang, Lei [The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis, Collaborative Innovation Center for Environmental Toxicity, Guangzhou Medical University, Guangzhou 510182 (China); Zhou, Yifeng [Soochow University Laboratory of Cancer Molecular Genetics, Collaborative Innovation Center for Environmental Toxicity, Medical College of Soochow University, Suzhou 215123 (China); Lu, Jiachun, E-mail: jcLu@gzhmu.edu.cn [The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis, Collaborative Innovation Center for Environmental Toxicity, Guangzhou Medical University, Guangzhou 510182 (China)

2014-12-15

Highlights: • NBS1 rs1805794G>C polymorphism conferred an adverse role on lung cancer risk in a two centers case–control study. • Rs1805794C variants had more chromatid breaks and higher DNA damage induced by X-ray radiation. • Meta analysis result confirmed the association between the variant rs1805794G>C and lung cancer risk. - Abstract: NBS1 plays pivotal roles in maintaining genomic stability and cancer development. The exon variant rs1805794G>C (p.Glu185Gln) of NBS1 has been frequently studied in several association studies. However, the results were conflicting. Also, the function of this variant has never been well studied. In the current study, we performed a two centers case–control study and function assays to investigate the effect of the variant rs1805794G>C on lung cancer risk in Chinese, and a meta-analysis to summarize the data on the association between rs1805794G>C and cancer risk. We found that compared with the rs1805794GG genotype, the C genotypes (CG/CC) conferred a significantly increased risk of lung cancer in Chinese (OR = 1.40, 95% CI = 1.21–1.62) and interacted with medical ionizing radiation exposure on increasing cancer risk (P{sub interaction} = 0.015). The lymphocyte cells from the C genotype individuals developed more chromatid breaks than those from the GG genotype carriers after the X-ray radiation (P = 0.036). Moreover, the rs1805794C allele encoding p.185Gln attenuated NBS1's ability to repair DNA damage as the cell lines transfected with NBS1 cDNA expression vector carrying rs1805794C allele had significantly higher DNA breaks than those transfected with NBS1 cDNA expression vector carrying rs1805794G allele (P < 0.05). The meta-analysis further confirmed the association between the variant rs1805794G>C and lung cancer risk, that compared with the GG genotype, the carriers of C genotypes had a 1.30-fold risk of cancer (95% CI = 1.14–1.49, P = 8.49 × 10{sup −5}). These findings suggest that the rs1805794G

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

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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

Effect of Antiviral Agents in Equine Abortion Virus-Infected Hamsters1

Science.gov (United States)

Lieberman, Melvin; Pascale, Andrea; Schafer, Thomas W.; Came, Paul E.

1972-01-01

Equine abortion virus, a member of the herpesvirus group, produces a lethal infection in hamsters. With this system, the protective effect of certain inhibitors of deoxyribonucleic acid viruses, inducers of interferon and exogenous interferon, was evaluated. Of the various agents studied, 9-β-d-arabinofuranosyladenine markedly suppressed mortality, and 5-iodo-2′-deoxyuridine, distamycin A, and N-ethylisatin β-thiosemicarbazone were inactive. Of the inducers tested, statolon, ultraviolet-irradiated Newcastle disease virus, and polyriboinosinic:polyribocytidylic acid (poly I:C) were protective, and endotoxin, polyacrylic acid, and polymethacrylic acid did not protect. Administration of exogenous interferon did not afford protection. Statolon and ultraviolet-irradiated Newcastle disease virus induced circulating interferon in hamsters, whereas poly I:C, endotoxin, and polyacrylic acid did not produce interferon. Because of the severity of the disease produced in hamsters by equine abortion virus, lack of protective activity by an agent in this system should not preclude possible efficacy against other members of the herpesvirus group. PMID:4376907

A functional polymorphism at microRNA-629-binding site in the 3'-untranslated region of NBS1 gene confers an increased risk of lung cancer in Southern and Eastern Chinese population.

Science.gov (United States)