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  • 1
    Call number: 04-GEN:168a
    Keywords: Aneuploidy / Congresses ; Chromosome abnormalities / Congresses ; Aneuploidy / Congresses ; Chromosome Aberrations / etiology
    Notes: "Extended versions of approximately one half of the papers delivered to the conference"--Pref.
    Pages: xviii, 400 p. : ill.
    ISBN: 0845151681
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    04-GEN:168a departmental collection or stack – please contact the library
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  • 2
    ISSN: 1432-0886
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. The centromeres of a genome separate in a sequential, nonrandom manner that is apparently dependent upon the quantity and quality of pericentric heterochromatin. It is becoming increasingly clear that the biological properties of a centromere depend upon its physicochemical makeup, such as its tertiary structure, and not necessarily on its particular nucleotide sequence. To test this idea we altered the physical state of the AT-rich pericentric heterochromatin of mouse with Hoechst 33258 (bis-benzimidazole) and studied a biological parameter, viz., sequence of separation. We report that an alteration in the physical state of heterochromatin, i.e., decondensation, is accompanied by aberrations in the pattern of centromere separation. The most dramatic effect seems to be on chromosomes with large blocks of heterochromatin. Many chromosomes with large blocks of heterochromatin that, in untreated cells, separate late tend to separate early. Decondensation with Hoechst 33258 does not seem to alter the sequence of separation of inactive centromeres relative to that of active centromeres. These data indicate that alteration in the physical parameters of the pericentric heterochromatin might dispose the centromeres to errors. It is likely that this aberration results from early replication of the pericentric heterochromatin associated with active centromeres.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Human genetics 〈Berlin〉 57 (1981), S. 247-252 
    ISSN: 1432-1203
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Mitotic chromosomes from human peripheral lymphocytes studied at the junction of metaphase and anaphase show that the centromeres of various chromosomes separate in a nonrandom, apparently genetically controlled sequence. It does not depend upon the position of the centromere in the chromosome, the length of the chromosome or total amount of detectable C-chromatin. In man, several chromosomes e.g. 18, 17, 2, separate very early. Such “early” cells do not include nos. 1, 13, 14, 15, and Y and very rarely nos. 21 and 22. The last separating chromosomes are those from group D, G, no. 1, 16, and Y. The possible implication of these findings in evolution, non-disjunction and the control of centromere separation sequences is discussed.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0886
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The B1 cell line of rat cerebral endothelium origin exhibits several dicentric and multicentric chromosomes. These chromosomes, unlike multicentrics in mouse (Vig and Zinkowski 1986) do not show premature centromere separation. All centromeres deposit kinetochore proteins and appear to be functional. Even the centromeres which fail to migrate to the poles during anaphase and make side arm bridges bind to spindle microtubules. Some multicentric chromosomes show kinetochores spaced apart with intervening stretches of euchromatin while others are located adjacent to each other thus exhibiting tandem repeats and forming a “compound” kinetochore (Brinkeley et al. 1984). Also, unlike mouse multicentric chromosomes in which different pericentric regions and the centromeres replicate at different times, the rat chromosomes appear to replicate all pericentric and centric regions in a given multicentric simultaneously. The present studies indicate that centromeres in rat and mouse replicate during the last part of the S-phase and in continuation with the pericentric heterochromatin.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0886
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract A transformed cell line, B1, of cerebral endothelial origin from the Wistar-Kyoto male rat has chromatid and chromosome type bridges in virtually every cell. It exhibits various dicentric and polycentric chromosomes. Most dicentrics are symmetric isochromosomes. Certain isodicentrics are present in a fair segment of the cell population; however, almost all cells have some newly arising isodicentrics. The live cells show a lengthened prometaphase. Anaphase is also retarded possibly due to the occurrence of bridges. At anaphase some multicentrics split at only one centromere. When pulled to the two poles the unsplit centromeres and the distal chromosome segment form a side arm bridge. Another mechanism appears to be a total lack of separation of daughter centromeres at meta-anaphase (‘meiotic-like’ behavior of mitotic chromosomes). This is realized by the pulling of each of the two unsplit centromeres to opposite poles and results in bridges with both sister chromatids running parallel to each other. A break at corresponding weak points in the two sister chromatids followed by rejoining can form a dicentric isochromosome. A third mechanism, the breakage-fusion-bridge cycle, is also operative but would not produce isodicentrics. In the case of the first two mechanisms some or all centromeres apparently split between telophase and onset of the following DNA synthesis rather than at the usual time at late metaphase. These observations may suggest some previously unknown behavior of multicentric chromosomes during mitosis.
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  • 6
    ISSN: 1432-0886
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The dicentric and multicentric chromosomes in L cells and a brain tumor cell line of mouse display only one site of kinetochore formation associated with the ‘active’ centromere. The accessory or ‘inactive’ centromeres show premature separation. These cell lines were treated with 10−6 M 5-bromodeoxyuridine (BrdUrd) followed by anti-BrdUrd antibody to study the pattern of replication of pericentric heterochromatin flanking the active vs inactive centromeres. Regardless of its quantity, heterochromatin around the inactive centromere replicates earlier than that associated with the active centromere. There appears to be a relationship between the timing of separation of a centromere and the timing of replication of pericentric heterochromatin. The premature replication of heterochromatin associated with an inactive centromere may be responsible for its premature separation and, hence, inactivity.
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Cancer chemotherapy and pharmacology 3 (1979), S. 143-160 
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Considering the strong correlation observed between carcinogenic and mutagenic properties of chemicals, a study of the genetic effects of antineoplastic agents is warranted in as much as these agents may ‘cure’ certain types of cancers but may initiate some other types; in addition, an understanding of the effects of these antibiotics on possible transmissible alterations in the genetic material would be beneficial. The genetic effects of some antibiotic anticancer agents, viz., daunomycin (daunorubicin), adriamycin, bleomycin, actinomycin D, and mitomycin C are reviewed. Even though these are structurally unrelated (except for adriamycin and daunomycin), all these chemicals interfere with DNA synthesis through intercalation (daynomycin, adriamycin, and actinomycin), removal of basis from DNA (bleomycin), or co-valent bonding with DNA (mitomycin C) and strand breakage. In some case a parallelism is found between these chemicals and radiation (e.g., mitomycin C vs UV and bleomycin vs X-rays). All these chemicals have a reversible effect on the cell cycle only when applied at low concentrations. The G 0 stage is the most resistant and the S phase, the most sensitive to these chemicals, bleomycin having a general non-phase-specific effect. Actinomycin binds to chromatin differentially along the length of chromosome, and about 90% of this binding is with the DNA. Andriamycin, daunomycin and bleomycin also bind to chromatin, but not enough is known about differential binding. Phenomena such as enzymatic reduction, e.g., in the case of anthracyclines, seem to confer tissue specificity. The ability of actinomycin D to induce point mutations has been challeged, and most mutation-like effects appear to be epigenetic. The anthracyclines do not appear to be mutagenic either. Mitomycin C is mutagenic, however, perhaps because of its alkylating properties, as shown by studies with several species of micro-organisms, Drosophila, Habrobracon, mice, and human HLA system. Bleomycin has recently been shown to be a locus-specific mutagen in yeast. The study of chromosomes from lymphocytes and bone marrow of individuals receiving chemotherapy, and also in vitro studies, have revealed aberrations, an effect common to all other chemicals. However, the major effect is found when the treatment affects the S phase, except with bleomycin, which also happens to be the only chemical with an effect on prophase chromosomes. Mitomycin and bleomycin alos appear to effect the G 0 chromatin in mammals. The major effect of mitomycin C is the production of quadriradials by way of involving homologous chromosomes at corresponding, and preferentially heterochromatic, areas. No other chemical with such great specificity, has been found. Aberrations produced by mitomycin and actinomycin are exclusively of chromatid type, whereas others produce both chromatidand chromosome-type aberrations — both fragments and exchanges. The aberrations are localized in a nonrandom fashion along the length of the genome except with bleomycin, which does not show ‘hot sports’ as convincingly as other chemicals do. Mitomycin C, daunomycin, and adriamycin are very potent inducers of sister chromatid exchanges (SCEs), whereas bleomycin is a poor inducer of this phenomenon. There appears to be a cell-type specificity for induction of both chromosome aberrations and sister chromatid exchanges, though it is not the same at the two end points. The study of somatic crossing-over and meiotic effects has been confined primarily to plants, except for the study of meiotic phenomena in mice and Hebrobracon and Drosophila. Again mitomycin C turns out to be the most effective chemical in these regards. From these and other data on synergistic effects observed in a variety of organisms, there is an urgent need to draw conclusions on the effects of these chemicals on human genetic material in relation to transmissible changes, origin of neoplasia, and the control of cell growth as affected by genetic alterations brought about by these chemicals.
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  • 8
    ISSN: 1432-0886
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Chromosome preparations in late metaphase cells from bone marrow of colcemid treated male Chinese hamsters were used to analyse the sequence of separation of sister centromeres. Chromatids of chromosomes 2 and 1 are the first ones to separate at centromeres, followed by members of group B, D and C. Some acrocentric chromosome is always the last one to separate at the centromere. The data point to a possible correlation between the position of a centromere in the separation sequence in the genome and the amount of centromeric heterochromatin as well as relation to the phenomenon of non-disjunction.
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  • 9
    ISSN: 1432-0886
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Mouse L cells have many dicentric chromosomes and one with eight centromeres. All eight centromeres behave similarly until midmetaphase when most centromeres split into two units each in apparently quick succession but out-of-phase. This premature separation leaves one or perhaps two closely located centromeres intact, which separate at late metaphase-anaphase, drawing the two chromatids to opposite poles. Such dominance of one centromere over all others, though unexplained, ensures the lack of any mitotic abnormality such as bridges or fragments. These observations show that all the centromeres are retained as functional primary constrictions except for a change in functional regulation when more than one centromere are located on a chromosome.
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  • 10
    ISSN: 1432-0886
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Long-term cultures of certain rat and mouse cell lines carry several dicentric and some multicentric chromosomes. Using antikinetochore antibodies obtainable from serum of scleroderma (var. CREST) patients we studied the number of kinetochores formed along the length of these chromosomes. The rat cells displayed as many kinetochores as there were centromeres. However, mouse cells showed the synthesis of only one kinetochore in dicentric and multicentric chromosomes which had been in the culture for a period of 1 year or more. When translocations were induced by bleomycin in mouse L cells, the newly formed dicentric chromosomes showed the formation of two kinetochores. It is not known when the accessory centromeres lose their capacity to assemble kinetochore proteins. Possibly, in the rat the ‘latent’ kinetochores lack a specific component which renders them ineffective for microtubule binding. The reason for the formation of only one kinetochore in mouse multicentric chromosomes is not clear. It may be due to the accumulation of mutations, modification of the kinetochore protein so that it lacks the antibody binding component, or a more effective regulatory gene than in the rat.
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