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  • Springer  (5)
  • 1
    Electronic Resource
    Electronic Resource
    Antitumor effects of gossypol on murine tumors (1985)
    Springer
    Cancer chemotherapy and pharmacology 15 (1985), S. 20-25 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Since the male antifertility drug, gossypol, was shown to be a specific inhibitor of DNA synthesis at moderately low doses in cultured cells, its antitumor potential has been evaluated in three murine tumor models. The effects of gossypol on tumor growth and the survival of 10-to 12-week-old BDF1 mice bearing mouse mammary adenocarcinoma 755 (Ca 755) or P388 or L1210 leukemias, all injected IP, were measured. At an optimum dose of 0.5 mg/mouse given as a single injection at 2 days (48 h) after the inoculation of 105 Ca 755 tumor cells, gossypol rendered 66% of the mice free of tumor cells, whereas the remaining 34% died of drug toxicity. The survival rate decreased sharply at doses on either side of the optimum. At suboptimal doses a major proportion of the tumor-bearing mice died of tumor, whereas at higher doses all the animals died of drug toxicity. In other words, the effective dose range of gossypol was rather narrow. The rapidly proliferating mouse leukemias, P388 and L1210, failed to respond to gossypol. Histopathological studies of various organs in the gossypol-treated mice revealed no consistent lesions that could give an indication of organ-specific toxicity of gossypol. The reduction in the myeloid series in the bone marrow of gossypol-treated mice may have been due to depletion rather than direct toxic effect. Further studies are essential to evaluate this compound with regard to its antitumor activity in other murine models.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00257288
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  • 2
    Electronic Resource
    Electronic Resource
    Mammalian cell fusion (1974)
    Springer
    Chromosoma 45 (1974), S. 121-131 
    Details
    ISSN: 1432-0886
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The behaviour of heterochromatin during premature chromosome condensation (PCC) was studied in a cell line of Microtus agrestis after fusion with mitotic HeLa cells. In the G1- and G2-PCC, the heterochromatic nature of the X-chromosomes was detectable by their intense staining. The pulverized appearance of the S-phase PCC was correlated with incorporation of 3H TdR into the DNA. Three types of S-PCC were observed. PCC with a pulverized appearance of: (a) only the autosomes (early S); (b) autosomes and X-chromosomes (mid S); and (c) only the X-chromosomes (late S). The behaviour of heterochromatin during replication, as observed by the PCC method, was no different from that of euchromatin. The data on the sequence of chromosome replication indicate that the centromeric regions of the X-chromosomes were the last segments to replicate. The completion of DNA synthesis in the X-chromosomes appears to be followed by progressive chromosome condensation during G2 even before the actual initiation of prophase.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00362306
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  • 3
    Electronic Resource
    Electronic Resource
    The phenomenon of premature chromosome condensation: its relevance to basic and applied research (1974)
    Springer
    Human genetics 〈Berlin〉 23 (1974), S. 235-258 
    Details
    ISSN: 1432-1203
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Description / Table of Contents: Zusammenfassung Die Chromosomen eukaryoter Zellen sind normalerweise nur für den kurzen Augenblick der Zellteilung sichtbar. Fusioniert man jedoch Mitosezellen mit Interphasezellen, so wird in den letzteren eine “vorzeitige Chromosomenkondensation” (engl.: premature chromosome condensation, PCC) induziert. Die Morphologie der vorzeitig kondensierten Chromosomen hängt von dem Stadium des Zellcyclus ab, in dem sich die Interphasetehen befinden: G1-Chromosomen sind sehr lange, einsträngige Gebilde, G2-Chromosomen bestehen aus zwei Chromatiden, die noch länger als Prophasechromosomen sind, und S-Chromosomen erscheinen “pulverisiert”, was offensichtlich auf eine stärkere Entspiralisierung des Chromatins an den Replikationsstellen zurückzuführen ist. Hiernach lassen sich heute einige ältere cytologische Befunde als vorzeitige Kondensation ganzer Chromosomensätze, einzelner Chromosomen und Chromosomenabschnitte interpretieren. Darüber hinaus haben die Untersuchungen an den vorzeitig kondensierten Chromosomen neue Einblicke in die Initiation der Mitose und den Kondensations-Dekondensations-Cyclus der Chromosomen während der Interphase ergeben. Die Anwendung dieser neuen Methode auf die Mutationsforschung und die klinische Cytogenetik wird diskutiert.
    Notes: Summary Normally the chromosomes of eukaryotic cells are visible only for a brief period during cell division. However, when mitotic cells are fused with interphase cells, a “premature chromosome condensation” (PCC) is induced in the interphase cells. The morphology of the prematurely condensed chromosomes varies according to the position of the interphase cell in the cell cycle: G1-PCC are very long and single-stranded; G2-PCC have two chromatids which are still longer than prophase chromosomes; S-PCC have a “pulverized” appearance, which is obviously due to less condensation of chromatin at the sites of replication. With this in mind, some older cytological findings can now be interpreted as premature condensation of whole chromosome sets, of single chromosomes, and of chromosomal regions. Furthermore, the studies on PCC shed new light on the initiation of mitosis and on the condensation-decondensation cycle of chromosomes during interphase. The application of this new method to mutagenesis and clinical cytogenetics is discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00272508
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  • 4
    Electronic Resource
    Electronic Resource
    Cell cycle-specific changes in the ultrastructural organization of prematurely condensed chromosomes (1983)
    Springer
    Chromosoma 88 (1983), S. 333-342 
    Details
    ISSN: 1432-0886
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Prematurely condensed chromosomes (PCC) of HeLa cells synchronized in different phases of the cell cycle were analyzed by high-resolution scanning electron microscopy. The purpose of this study was to examine changes in the arrangement of the basic 30-nm chromatin fiber within interphase chromosomes associated with progression through the cell cycle. These studies revealed that highly condensed metaphase chromosomes and early G1-PCC consisted of tightly packed looping fibers. Early to mid G1-PCC were more extended and exhibited gyres suggestive of a despiralized chromonema. Further attenuation of PCC during progression through G1 was associated with a gradual transition from packed looping fibers to single extended longitudinal fibers. This process occurs prior to the initiation of DNA synthesis which appears to be localized within single longitudinal fibers. Following replication of a chromosome segment, extended longitudinal fibers were rapidly reorganized into packed looping fiber clusters concomitant with the formation of a multifibered chromosome axis. This results in the characteristic “pulverized” appearance of S-PCC when viewed by light microscopy. Subsequently, adjacent looping fiber domains coalesce, resulting in the uniformly packed, looping fiber arrangement observed in G2-PCC. Spiralization of the chromonema during the G2-mitotic transition results in the formation of highly compact metaphase chromosomes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00285856
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  • 5
    Electronic Resource
    Electronic Resource
    The molecular basis of drug-induced G2 arrest in mammalian cells (1980)
    Springer
    Molecular and cellular biochemistry 29 (1980), S. 47-57 
    Details
    ISSN: 1573-4919
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Summary The purpose of this review was to focus mainly on the molecular events related to the progression of cells through the G2 period to examine the cause for G2-arrest in mammalian cells after exposure to various anticancer drugs. With few exceptions, most of the eukaryotic cells exhibit a G2 period in their life cycles. The G2 period, which separates S phase from mitosis, represents the time necessary for the synthesis of the various components related to the condensation of chromosomes, assembly of the mitotic spindle, and cytokinesis. Continued synthesis of RNA and protein is necessary for the successful completion of G2 and the initiation of mitosis. Inhibition of RNA and protein synthesis, replacement of phenylalanine by its analog parafluorophenylalanine, or the elevation of intracellular cAMP concentrations, induce reversible G2 arrest in cultured cells. Exposure of cells to certain antineoplastic drugs also blocks cells preferentially in G2. This irreversible drug-induced G2 arrest is associated with extensive chromosome damage. The G2-arrested cells were found to be deficient in certain proteins that may be specific for the G2-mitotic transition. These mitotic or chromosome condensation factors synthesized during the G2 period, reach their maximum levels at mitosis. A preliminary characterization of the chromosome condensation factor revealed that it is a heat labile, Ca2+-sensitive, nondialyzable protein with a sedimentation value of 4–5S.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00230954
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