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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intracisternal A particle preparations from a murine neuroblastoma cell line (N18) and from a mineral oil-induced murine plasmacytoma (MOPC-104E) contain both an endogenous RNA-dependent DNA polymerase activity and high molecular-weight polyadenylic acid (poly[A])-containing RNA. The DNA polymerase activity is stimulated by oligo(dG)-poly(C) and oligo(dT)-poly(A) and to a lesser extent by oligo(dT)-poly(dA), in agreement with previous reports. The high-molecular-weight RNA is predominantly 35S and contains a poly(A) tract of approximately 220 nucleotides as judged by polyacrylamide gel electrophoresis. Small amounts of 70S RNA are also present. This RNA preparation contains RNA homologous to RNA from type-C particles, as judged by molecular hybridization experiments. However, since this RNA derives only in part from A-particles and in part from other cellular RNA, hybridization of A-particle endogenously synthesized DNA or reverse transcripts of A-particle RNA to purified type C viral 70S RNA may more accurately reflect the relationship of A-particle RNA to RNA from C-particles. None of these DNA transcripts hybridizes significantly to C-particle 70S RNA, although MOPC and N18 DNA transcripts share significant homology. Our interpretation of these results is that murine intracisternal A particles are not closely related genetically to the tested murine type C viruses, although an alternate possibility is that all the A-particle DNA transcripts are copied from only a small part of the genome, which is unrelated to C-particle RNA.
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PMID:Murine intracisternal type A particles: a biochemical characterization. 5 37

Mouse neuroblastoma cells containing intracisternal type A particles were treated with iododeoxyuridine and dexamethasone to induce the release of type C oncornavirus particles. For 5 days after treatment, antigenic markers and DNA polymerase activities specific to particles of each of the two types were assayed in the cells and in pellets obtained by high-speed centrifugation of the culture fluid. There was a marked release of C-particle antigen (p30) and DNA polymerase activity in extracellular particulate form, reaching a maximum on day 3 after treatment and falling thereafter. In contrast, no extracellular A-particle antigen was detected, and A-particle-specific DNA polymerase activity in the medium pellets did not increase from the original very low level. Electron microscopy confirmed the presence of free type C virus particles, but not intracisternal type A particles, in the culture fluid. Although intracellular levels of C-particle antigen rose 20- to 30-fold per milligram of cell protein, intracellular A-particle antigen and DNA polymerase activity did not vary more than two-fold. The relative rate of A-particle synthesis in the treated cells, as judged by incorporation of radioactive amino acids into the major structural protein (P73), was also unchanged over the period of observation. Thus, the induction of type C virus particle formation in cultured neuroblastoma cells had no detectable effect on the quantity, synthesis rate, or location of intracisternal type A particles.
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PMID:Differential response of type C and intracisternal type A particle markers in cells treated with iododeoxyuridine and dexamethasone. 18 20

The activities of two DNA polymerases (DNA nucleotidyltransferases) were characterized in mouse neuroblastoma clone N-18 on the basis of their apparent molecular weights (determined by sucrose density gradient centrifugation: polymerase-alpha, 7.5-8 S; polymerase-beta, 3-4 S) and relative inhibition by sulfhydryl-blocking agents. N-Ethylmaleimide (10 mM) and iodoacetamide (1.5 mM) inhibited DNA polymerase-alpha activity completely, whereas only 35-40% inhibition was observed for DNA polymerase-beta under similar conditions. DNA polymerase-alpha activity was reduced 50-70% in N-18 cells that had been induced to differentiate by 4 micro M bromodeoxyuridine, and the low molecular weight DNA polymerase-beta activity remain unchanged. With activated calf thymus DNA as template, only DNA polymerase-alpha activity was stimulated in the presence of added ribonucleotides and purified Escherichia coli RNA polymerase.
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PMID:DNA polymerase activities in differentiating mouse neuroblastoma N-18 cells. 27 18

The effects of concanavalin A and ricin (RCAII, Mr 65,000) on [3H]thymidine incorporation into human neuroblastoma IMR-32 DNA showed reduction of total DNA synthesis to 50% and 70% of control, respectively. Two DNA polymerase (DNA nucleotidyltransferase, EC 2.7.7.7.) activities (alpha and beta) involved in the biosynthesis in vitro of DNA were separated by sucrose density gradient centrifugation from IMR-32 cell homogenate. The DNA polymerase alpha activity was also purified by selective precipitation with polyethylene glycol (Mr 6000) followed by agarose-concanavalin A column chromatography. The activities of both DNA polymerases were examined at various concentrations of mutagenic and nonmutagenic plant agglutinins and the toxin ricin. Concanavalin A and ricin specifically inhibited DNA polymerase alpha activity (activity reduced to 19% and 10%, respectively), whereas DNA polymerase beta activity was inhibited (reduced to 16%) by red kidney bean agglutinin (PHA-P).
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PMID:Inhibition of human neuroblastoma DNA polymerase activities by plant lectins and toxins. 28 62

The activity of nuclear DNA polymerases alpha, beta and delta/epsilon, uracil-DNA glycosylase, thymidine kinase and the presence of Proliferating Cell Nuclear Antigen (PCNA) have been examined in developing rat glial cells, in rat and human glioma, in human neuroblastoma and in differentiated neuroblastoma cell lines in vitro. During glial development the activity of all enzymes tested, except DNA polymerase beta, markedly decreased, suggesting their coordinate regulation in respect to the proliferative state of the cells. Glioma and neuroblastoma cell lines restore the enzymatic activities that were no longer expressed in normal adult cells. Neuroblastoma cell lines induced to differentiate in vitro by retinoic acid showed a decline of the activities of DNA polymerase alpha, DNA polymerase delta/epsilon, uracil-DNA glycosylase and thymidine kinase similar to that observed during in vivo differentiation. We also demonstrate that PCNA is not detectable in glial and neuronal cells at all developmental stages, but can be found in tumor nerve cells. A possible use of enzymatic assays or anti-PCNA antibodies to detect brain tumors is discussed.
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PMID:DNA synthesis enzymes and proliferating cell nuclear antigen in normal and neoplastic nerve cells. 135 31

Treatment of the neuroblastoma cell line SHSY5Y with nerve growth factor (NGF) resulted in limited neurite extension, but proliferation continued. However, SHSY5Y cells treated with NGF and a pulse of the DNA polymerase alpha and delta inhibitor aphidicolin showed dramatic neuronal differentiation. Few differentiated cells were observed immediately following the NGF-aphidicolin treatment; however, continued treatment of the cells with NGF in the ensuing week resulted in extension of long neurites (> 400 microns). Neurite extension was not observed for cells treated with aphidicolin alone. Hence, aphidicolin and NGF act synergistically to induce differentiation of SHSY5Y cells. If maintained in NGF, the differentiated cells were stable for at least 1 month and displayed many neuronal characteristics. They were mitotically inactive, and, in contrast to control or NGF-treated cells, the differentiated cells required NGF for survival. The cells expressed multiple microtubule-associated proteins (MAP), including MAP 1A, MAP 1B, and tau. There was expression of synaptic vesicle antigens synaptophysin and SV2, but not synapsin Ia/b or synapsin IIa/b. Both hydroxyurea and thymidine, which inhibit synthesis of nucleotides, act synergistically with NGF to induce differentiation of SHSY5Y cells. Since aphidicolin, hydroxyurea, and thymidine are chemically unrelated, we conclude that these drugs enhance NGF-induced differentiation by blocking cell proliferation and not through an unrelated side effect. The model suggested by these studies is that differentiation is triggered by two simultaneous signals: NGF and cessation of cell proliferation.
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PMID:Neuronal differentiation triggered by blocking cell proliferation. 141 12

Aphidicolin is a tetracyclic diterpene antibiotic which is known to inhibit the growth of eucaryotic cells by reversible binding to DNA polymerase alpha without significant effect on cell viability in most common human cell lines. We observed that aphidicolin at a concentration of 5 x 10(-7) M kills all cells of four human neuroblastoma cell lines. In contrast, viability of normal human embryonal cells and of human continuous cell lines including HeLa, H9, A549 and Caco-2 was influenced only moderately by aphidicolin. In addition, neuroblastoma cells were killed after treatment with 5 x 10(-7) M aphidicolin in cocultures with normal embryonal cells which continued to proliferate after removal of aphidicolin. These results show that aphidicolin provides an agent which selectively kills neuroblastoma cells in vitro.
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PMID:Aphidicolin selectively kills neuroblastoma cells in vitro. 148 68

The purpose of the present study was to examine the distribution pattern of acridine orange (AO) chromatin interaction products (AOCI) in human neuroblastoma IMR-32 cells and to test whether AO labeling is correlated with BrdU incorporation, and immunohistochemical localization of DNA polymerase alpha, and human N-myc-gene product. Effects of aphidicolin, alpha-amanitin, and actinomycin D on visualization of AO binding to euchromatin and on N-myc-gene expression were also examined. About 25% of the cell nuclei in logarithmic growth phase were immunohistochemically demonstrated to be labeled with BrdU after incubation at 37 degrees for 30 min, indicating cells in DNA synthesis. Most of the cell nuclei showed positive immunoreactivity to DNA polymerase alpha, while human N-myc gene product was found in about 60-80% of the cell nuclei. Electron microscopic studies revealed that about 25% of neuroblastoma cells showed characteristic AOCI within cell nuclei. In the presence of aphidicolin, alpha-amanitin, and actinomycin D, positive cells for N-myc gene product decreased markedly. Percentages of AO positive cells and numbers of AOCI per cell nucleus also showed a marked decrease. But northern blot analysis demonstrated that the expression level of N-myc gene was only repressed by the transcriptional inhibitors alpha-amanitin and actinomycin D. However, no repression was caused by aphidicolin. The present and previous studies of the authors suggest that the ultracytochemical AO method may be indicative for conformational changes of chromatin of cells confined to the cell cycle. Inhibitors of RNA and DNA synthesis then may change the conformational state of chromatin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Electron microscopic localization of acridine orange binding to euchromatin in human neuroblastoma cells. 190 67

RNA blot hybridization analysis revealed that the steady-state level of DNA polymerase beta-mRNA in mouse neuroblastoma N18TG2 cells was approximately five-fold higher than that in NIH/3T3 cells. In order to examine the function of DNA polymerase beta-gene silencers in these two cell lines, we employed a chloramphenicol acetyltransferase (CAT)-transient expression assay using the CAT plasmids containing the silencers linked to various promoter-enhancers. In NIH/3T3 cells, DNA polymerase beta-gene silencers effectively repressed the function of its own promoter and those of several other heterologous promoter-enhancers. In contrast, the silencers only marginally affected the CAT expression directed by DNA polymerase beta-gene promoter and heterologous promoter-enhancers in N18TG2 cells. The extent of the increase of CAT expression by removing silencer elements in NIH/3T3 cells was very similar to the ratio of DNA polymerase beta-mRNA content in N18TG2 cells to that in NIH/3T3 cells. These results indicate that cell-type-specific expression of DNA polymerase beta-gene is primarily controlled by the function of its silencer elements.
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PMID:Cell-type-specific expression of mouse DNA polymerase beta-gene is regulated by silencer elements. 280 47

HSV-1(17) replicates 100-fold more efficiently than HSV-2(186) within trigeminal ganglia following ocular infection. In order to identify the nucleotide sequences responsible for the differences in the capacity of the two HSV strains to grow within the peripheral nervous system, an intertypic recombinant was generated by infecting neuroblastoma cells with HSV-2(186) and a HSV strain possessing nucleotide sequences from HSV-1(17). The genome of the intertypic recombinant was composed entirely of HSV-2(186) DNA except for 2.0 kb of HSV-1(17) DNA positioned between m.u. 0.413 and 0.426. Following corneal infection of mice, the intertypic recombinant grew to higher titers in both ocular tissues and trigeminal ganglia than did the HSV-2 parent. Most significantly, the intertypic recombinant could spread into the brain from the trigeminal ganglion and kill the host whereas mice inoculated with the HSV-2(186) parent survived infection. The 2.0 kb of HSV-1(17) DNA inserted into the genome of the intertypic recombinant encodes the 5' terminus of the HSV-1 gene for DNA polymerase. Thus, the results suggest that the difference in the capacity of two HSV strains to replicate within the trigeminal ganglion of its host and to spread into the brain is determined by nucleotide sequences within the gene for DNA polymerase.
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PMID:Evidence that the gene for herpes simplex virus type 1 DNA polymerase accounts for the capacity of an intertypic recombinant to spread from eye to central nervous system. 283 53


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