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  • 1
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    Lindsay, Kennedy, and the Power Struggle in New York (1966)
    New York, N.Y. : Periodicals Archive Online (PAO)
    Harper's. 232:1388 (1966:Jan.) 37 
    Details
    ISSN: 0017-789X
    Topics: General, Interdisciplinary
    URL: http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&res_dat=xri:pao:&rft_dat=xri:pao:article:5128-1966-232-88-000001
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  • 2
    Electronic Resource
    Electronic Resource
    Induction and reversion of asparagine auxotrophs in CHO-K1 and V79 cells (1986)
    Springer
    Somatic cell and molecular genetics 12 (1986), S. 459-466 
    Details
    ISSN: 1572-9931
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Two asparagine-dependent clones (2002-103 and 2002-109) were obtained from CHO-K1 cells by treatment with EMS followed by a BrdU-black light selection procedure; an additional ASP− clone (2293-343) was isolated similarly from V79-56 cells. All three clones show a low rate of spontaneous reversion which is increased somewhat by exposure to EMS. Two of the variant clones (2002-103 and 2002-109) are converted in high frequency to asparagine independence by treatment with 5-azacytidine, while 2293-343 cells show no significant induction after similar exposure. All threeASP − clones were found by hybrid analyses to belong to the same complementation group. Treatment of hybrids constructed between 2002-103 or 2002-109 × 2293-343 with 5-azacytidine resulted in high-frequency induction of asparagine independence. Thus, the potential for response to 5-azacytidine in such hybrids by reversion to asparagine independence is dominant or codominant, with no suppressor effect in hybrids from the nonresponsive parent line.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01539917
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  • 3
    Electronic Resource
    Electronic Resource
    Simultaneous induction of epigenetic variants (1986)
    Springer
    Somatic cell and molecular genetics 12 (1986), S. 567-573 
    Details
    ISSN: 1572-9931
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Epigenetic changes at one, two, or three loci were induced with 5-azacytidine in CHO-K1 cells, using markers (proline dependence, asparagine dependence, and thymidine kinase deficiency) which respond by high-frequency reversion to wild-type states. The observed incidence of dual or triple revertants was compared with the frequency expected by chance as the product of single frequencies measured separately for the markers involved. Values observed for dual reversions consistently exceeded levels predicted by this purely stochastic model, and for triple reversion the divergence was 1000-fold. Coordinate responses could account for this disparity, if minority cell types with higher reactivity to 5-azacytidine exist in target cell populations. To test this hypothesis, single colonies were isolated under nonselective conditions from a mass culture of CHO-K1 cells that had been treated with 5-azacytidine. These clones showed wide and reproducible differences in competence for reversion from proline dependence to independence. Our data thus suggest that simultaneity of epigenetic changes depends on random events which are modulated by a mosaic of inductive potentials within individual cells of the reacting system.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01671942
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  • 4
    Electronic Resource
    Electronic Resource
    Genetic and adaptive differences in the expression of drug resistance in hybrid cells (1979)
    Springer
    Somatic cell and molecular genetics 5 (1979), S. 793-807 
    Details
    ISSN: 1572-9931
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Hybrids between Chinese hamster cells were isolated and maintained in media that were selective or nonselective for markers present in the parent cells (HGPRT and TK deficiencies, respectively). Segregation frequencies for resistance to azaguanine (AZG), thioguanine (THG), or bromodeoxyuridine (BrdU) could be enhanced for some groups of hybrids if the stock cells were maintained under nonselective conditions rather than in HAT medium. In these populations the expression of resistance was dominant or codominant even though marker patterns were recessive for the same cells in HAT. Clonal analysis showed that enhancement took place by adaptive shifts rather than by variation and selection. Segregation frequencies in hybrids were also found to differ significantly between clones isolated by replicate fusions of any two parental cell types. The basis for this heterogeneity is unknown and deserves further study.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01542642
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  • 5
    Electronic Resource
    Electronic Resource
    Osmotic stress variants in Chinese hamster cells (1993)
    Springer
    Somatic cell and molecular genetics 19 (1993), S. 439-447 
    Details
    ISSN: 1572-9931
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Stable variants resistant to hypertonic stress have been obtained from V79 cells by one-step selection in media supplemented with graded concentrations of NaCl. Such variants retain a potential for resistance when isolated and propagated in isotonic media. On replating in graded NaCl, a family of dose-response curves is obtained, rising in level of resistance according to the degree of hypertonicity used to isolate the variants initially. In hybrids between variants and sensitive cells, phenotypic expression of resistance to hypertonic NaCl is recessive. Stable variants can also be isolated by one-step selection in media made hypertonic with D-mannitol. Clonal sublines selected with mannitol, as well as those obtained with NaCl, are resistant to both types of hypertonic media. Fluctuation tests in media supplemented with NaCl show that resistance arises spontaneously and at random, with measured rates of variation that depend on the concentration of NaCl used for selection. Treatment of sensitive cells with 5-azacytidine increases the frequency of resistant variants in assays with high levels of added NaCl but is less effective when selection is performed at lower concentrations. Exposure to ethyl methane sulfonate has little or no effect on variant frequency.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01233249
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  • 6
    Electronic Resource
    Electronic Resource
    Variants inducible for glutamine synthetase in V79-56 cells (1984)
    Springer
    Somatic cell and molecular genetics 10 (1984), S. 275-281 
    Details
    ISSN: 1572-9931
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract V79-56 cells have an absolute requirement for exogenous glutamine and are not inducible for glutamine synthetase. Prototrophs arise spontaneously at approximately 1.0 × 10−5 per cell per generation as measured by fluctuation tests. Higher frequencies of glutamine-independent variants may be obtained by treatment with the mutagen ethyl methane sulfonate, as well as by exposure to 5-azacytidine and sodium butyrate, which act primarily by affecting gene expression. Variants of all types show marked elevation of glutamine synthetase activity. Although this activity declines toward constitutive levels in the presence of glutamine, it is still inducible in variant cells. These populations, after a lag, regain the ability for progressive growth in glutamine-free medium. Thus, the stable variation seen here is in the potential for induction, rather than steady-state expression of glutamine synthetase at a higher level.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01535249
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  • 7
    Electronic Resource
    Electronic Resource
    Pyruvate blocks expression of sensitivity to antimycin A and chloramphenicol (1980)
    Springer
    Somatic cell and molecular genetics 6 (1980), S. 699-708 
    Details
    ISSN: 1572-9931
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Selectivity in Chinese hamster cells with antimycin A and chloramphenicol depends on a metabolic balance which can be modulated by varying the level of exogenous pyruvate. The effects of both inhibitors are most clearly seen in pyruvate-free nutrients. Addition of 1 mM pyruvate in plating assays shifts dose-response curves for antimycin A or chloramphenicol to higher concentration levels and reduces the differential in response between sensitive and resistant cells. In mass populations, growth inhibition by antimycin A is reduced by adding pyruvate, and growth curves for sensitive and resistant cells tend to converge. These observations show that responses to antimitochondrial drugs can be conditioned by extrinsic factors and indicate the need for further definition of selective systems.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01538969
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  • 8
    Electronic Resource
    Electronic Resource
    Deletion and hypermethylation of thymidine kinase gene in V79 Chinese hamster cells resistant to bromodeoxyuridine (1988)
    Springer
    Somatic cell and molecular genetics 14 (1988), S. 567-581 
    Details
    ISSN: 1572-9931
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Previous studies on V79 Chinese hamster cells have shown that bromodeoxyuridine (BrdU)-resistant variants deficient in thymidine kinase (TK) activity arise by a multistep process which is initiated by a random event and progresses gradually during serial culture in the presence of the drug. In order to determine the molecular basis for the loss of TK activity in these cells, the TK gene was isolated from a λ phage library of genomic V79 DNA, using a fragment of the human TK gene as a probe. One phage isolated contained the entire TK gene in a 15-kb insert, as demonstrated by the ability of the phage DNA to transform Ltk}-mouse cells to the TK+ phenotype. Five fragments spanning the entire gene were then subcloned into the plasmid pUC12 for DNA methylation studies. With these probes it was shown by hybridization analysis that the copy number of the TK gene in V79 cells is about four times the copy number in CHO cells and Chinese hamster liver cells. Southern hybridization analysis of the DNA from first-stage variants partially resistant to BrdU indicated that partial resistance was accompanied by deletion of a number of copies of theha TK gene in V79 cells. However, the subsequent gradual transition to full BrdU resistance and full loss of TK activity was correlated with a gradual hypermethylation of sites in the 5′ region of the TK gene, with no further change in gene copy number.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01535311
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  • 9
    Electronic Resource
    Electronic Resource
    High-frequency induction by 5-azacytidine of proline independence in CHO-K1 cells (1984)
    Springer
    Somatic cell and molecular genetics 10 (1984), S. 615-624 
    Details
    ISSN: 1572-9931
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Proline independence in CHO-K1 Chinese hamster cells has in previous studies been characterized as an auxotrophic gene mutation. In the absence of direct proof, an alternative model must be considered, based on suppression of proline synthesis by DNA methylation changes at one or more loci concerned. This concept receives strong support from the present study, in which we show that treatment of CHO-K1 cells with 5-azacytidine induces a 105–106 increase in background conversion to the proline-independent state. Revertants thus obtained, as well as those arising spontaneously or after treatment with ethyl methane sulfonate, are stable phenotypically in the presence or absence of proline. Proline independence in all variants examined was correlated with increased activity of pyrroline-5-carboxylate synthase. Four of five variants induced with 5-azacytidine showed simultaneous increases in activity of ornithine aminotransferase as well. Our data suggest that epigenetic, rather than genetic changes, underlie the transitions between proline dependence and independence in CHO-K1 cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01535227
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  • 10
    Electronic Resource
    Electronic Resource
    Evolution of growth responses to spleen protein in cultures of pig kidney cells (1965)
    Springer
    Cell & tissue research 68 (1965), S. 494-501 
    Details
    ISSN: 1432-0878
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary 1. Freshly isolated pig kidney cells grow poorly in a serum-supplemented synthetic medium, and are markedly stimulated by adult spleen protein fractions. Derivative strains after 30 or more passages develop a limited potential for growth in the absence of spleen protein; permanent cell populations proliferate rapidly without additives. 2. The effect of spleen fractions on cell cultures is related to population density, and can be duplicated in part by increasing the starting inoculum. Cultures initiated with low cell numbers fail to proliferate in the absence of spleen supplements. 3. Acquisition of independence from the growth-promoting effects of spleen fraction is correlated with a rise in plating efficiency, i.e., ability of isolated single cells to proliferate as clones. 4. Activity of spleen protein extracts in primary cell cultures is nondialyzable, pHsensitive, and heat resistant. Growth facilitation in this system appears to depend on a protective or supportive action by protein factors on the cell surface.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00347713
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