Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.7 (DNA polymerase)
 17,007 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have described the in vitro isolation of type-C RNA viruses from two outbreaks of a fatal neoplastic disease in turkeys we diagnosed as reticuloendotheliosis. The virus had a density of 1.16 g/ml in sucrose gradients, had a DNA polymerase capable of using both endogenous and exogenous (synthetic) templates, and was infectious in vitro for turkey and chick cells. The culture-propagated virus was oncogenic for turkeys. The virus isolates were unrelated to avian leukosis virus and antigenically identical to reticuloendotheliosis virus (REV) strain T. Thus our studies suggested that REV is a causative agent of naturally occurring, fatal leukosis in turkeys.
J Natl Cancer Inst 1975 Jun
PMID:Isolation and characterization of viruses from natural outbreaks of reticuloendotheliosis in turkeys. 16 89

Incorporation of [3H]TTP into membrane-denuded nuclei and fractions of these nuclei from host liver and Morris hepatomas has been compared. Treatment of sucrose nuclei with Triton X-100 removed 95% of the phospholipids and 15 to 20% of the protein. These membrane-denuded nuclei remained physically stable. The Triton X-100-extracted nuclei incorporated label into their DNA in nuclear-incorporating system similar to sucrose nuclei with their membranes intact. Triton X-100-treated nuclei from hepatoma 7777 incorporated six times more label and those from hepatoma 7800 incorporated three times more label than Triton X-100-treated host liver nuclei. Nuclei from the three sources incorporated more label when exogenous DNA was added to the incubation system, but the difference in incorporation between the hepatoma nuclei and the host liver nuclei disappeared. When Triton X-100-treated nuclei, prepared from a tumor-bearing animal given injections of [3H]thymidine for 10 min were fractionated on sucrose gradients after disruption by high Mg2+ concentration, the fractions from hepatoma 7777 nuclei contained six times as much label as the host liver nuclear fractions. Nuclear fractions prepared from unabeled hepatomas or host livers had DNA polymerase activity. The activity, however, is the same in fractions prepared from hepatoma 7777 or host liver nuclei. It is suggested that the nuclear membrane does not play an important role in nuclear DNA synthesis. It is further suggested that the increased incorporation found with hepatoma nuclei is dependent on a physical or chemical arrangement of components within the nucleus and not solely on different enzyme levels.
Cancer Res 1975 Oct
PMID:DNA synthesis in membrane-denuded nuclei and nuclear fractions from host liver and Morris hepatomas. 16 67

Primary mammary tumor cultures of RIII, GR, DD, BALB/c, and BALB/cfC3H mice were examined for mouse mammary tumor virus (MuMTV) production. Levels of production of 12-32 mug virus protein/day/75-cm2 culture flask could be maintained for 30-50 days with daily virus harvests. The viruses from tumor cell cultures of these mouse strains contained DNA polymerase with a strong preference for Mg++ over Mn++ as the divalent cation, a characteristic of DNA polymerase of MuMTV from mouse milk. These viruses from tumor cell cultures were excellent sources of MuMTV 3H-complementary DNA (complexed to 60-70S RNA) and radioactive 60-70S RNA, sufficiently free of contaminating murine leukemia virus nucleic acids, that can be used in molecular hybridization experiments. The effects of several culture parameters on MuMTV production were also studied.
J Natl Cancer Inst 1976 Jan
PMID:Characterization of mouse mammary tumor viruses from primary tumor cell cultures. II. Biochemical and biophysical studies. 17 74

Phosphonoacetate (PA), but not any of its analogues tested, effectively inhibited avian herpesvirus replication and viral DNA synthesis in cell cultures. At 100 mug/ml culture medium, PA completely inhibited the replication of Marek's disease virus (MDV), herpesvirus of turkeys, and owl herpesvirus, but had no measurable effect on normal cell growth. PA also inhibited DNA polymerases induced by these avian viruses. Enzyme inhibition was 50% at a PA concentration of 0.2 mug/ml. At a concentration of 3-6 mug/ml, the compound also effected a 50% inhibition of alpha (maxi) enzyme of the host DNA polymerase. It had no effect on the host beta (mini) enzyme. When administered to chickens, PA did not inhibit the replication of MDV, nor did it prevent the development of lymphoma.
J Natl Cancer Inst 1976 Apr
PMID:Effect of phosphonoacetate on Marek's disease virus replication. 17 10

Incubation of HeLa cells with the anticancer agent N-methyl-N-nitrosourea (MNU) results in: (a) depression of intracellular nicotinamide adenine dinucleotide levels; (b) stimulation of the chromatin-associated, chromosomal protein-modifying enzyme polyadenosine diphosphoribose [poly(ADP-ribose)] polymerase, which uses nicotinamide adenine dinucleotide as substrate; and (c) some fragmentation of cellular DNA. DNase treatment of HeLa nuclei in vitro also stimulates poly(ADP-ribose) polymerase activity, but not in nuclei derived from MNU-treated cells unless they have been subsequently incubated to allow for recovery from MNU damage. DNA polymerase activity is stimulated in vitro by poly(ADP) ribosylation of nuclear proteins. By using intact nuclei derived from MNU-treated HeLa cells, the repair via elongation of single-strand DNA breaks is demonstrated in vitro. This repair is dependent on DNA polymerase activity and is enhanced by adenosine diphosphate ribosylation of histones. Inhibition of poly(ADP-ribose) polymerase with nicotinamide results in extensive degradation of MNU-damaged DNA. Taken as a whole, these results suggest that poly(ADP-ribose) polymerase may play a role in the repair of alkylation damage to cellular DNA and that the inhibition of this enzyme in vivo might be exploited to potentiate the antitumor and carcinogenic activities of MNU.
Cancer Res 1977 Sep
PMID:A putative role for nicotinamide adenine dinucleotide-promoted nuclear protein modification in the antitumor activity of N-methyl-N-nitrosourea. 19 15

Tilorone, which is 2,7-bis[2-(diethylamino)ethoxy]-9H-fluoren-9-one dihydrochloride, and 13 of its analogs inhibited human cellular DNA polymerases alpha and beta assayed with activated DNA as template and also cellular DNA polymerase gamma and DNA polymerase from simian sarcoma virus assayed with poly(A) (dT)12-18 as template. Terminal deoxynucleotidyltransferase (TdT), which has no template requirement, was not inhibited by any of the 14 compounds when d(A)12-18 or d(G)12-18 was used as initiator. Three compounds did not inhibit TdT assayed with activated DNA as initiator, but 11 compounds did, and these 11 compounds were generally less inhibitory to TdT than to the other DNA polymerases. The three compounds that did not inhibit TdT assayed with activated DNA but did inhibit the other DNA polymerases will be useful in the characterization of TdT activity. Modifications of the polycyclic ring structure of tilorone and the kinds of substituent groups attached to the ring structures influenced the degree of inhibition of all enzymes.
J Natl Cancer Inst 1978 Mar
PMID:Inhibition of deoxynucleotide-polymerizing enzyme activities of human leukemia lymphoblasts and simian sarcoma virus by tilorone and thirteen of its analogs. 20 9

A DNA polymerase (DNA nucleotidyltransferase) has been partially purified from a neck mass of an American patient with Burkitt lymphoma and separated from the cellular DNA polymerases. The molecular weight of the enzyme was approximately 90,000. The enzyme differs from the cellular DNA polymerases, but resembles herpes-virus-induced DNA polymerase in its primer template preference, high monovalent cation requirement for activity, and sensitivity to phosphonoacetate. Enzyme activity was inhibited specifically by an antibody directed against herpes-simplex-virus-induced DNA polymerase but not by antibodies directed against DNA polymerase alpha of HeLa cells and DNA polymerase gamma of a normal human lymphoblast cell line, NC37. Although serum of the patient with Burkitt lymphoma contained high Epstein-Barr virus titer, addition of the serum to the assay mixture did not have any effect on the activity of Burkitt lymphoma DNA polymerase. Tissues from spleen and liver of the patient with Burkitt lymphoma did not contain the herpes-virus-induced DNA polymerase. Detection of the herpes virus polymerase in the Burkitt lymphoma tissue provides additional evidence for the association of Epstein-Barr virus with this malignancy.
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PMID:Isolation of a herpesvirus-specific DNA polymerase from tissues of an American patient with Burkitt lymphoma. 21 56

Eight cell lines were established from murine osteosarcomas induced in vivo with the radionuclides 224Ra and 227Th. They have been compared by light and electron microscopy, by karyology, and by their growth properties. The morphology, the growth pattern, and the ability to induce tumors in mice indicate that five of them are tumor cell lines. Chromosome studies demonstrated that the five cell lines have marker chromosomes. The other cell lines only showed some criteria generally used to score for transformation of fibroblasts and they may be derived from stromal cells. All cell lines release virus particles in the culture fluid which have the typical properties of RNA tumor viruses. They possess C-type morphology, a density of 1.16--1.18 g/cm3, a 60--70 S RNA, a RNA dependent DNA polymerase and they induce syncytia in rat XC cells. The possible significance of these virus particles in radiation osteosarcomagenesis is discussed.
J Cancer Res Clin Oncol 1979 Jun 08
PMID:Establishment and characterization of C-type RNA virus-producing cell lines from radiation-induced murine osteosarcomas. 22 67

Previous studies have identified human breast tumor particles possessing many of the features characteristic of RNA tumor viruses. In addition to the expected size (600 S) and density (1.16 g/ml) these include possession of an outer membrane and an inner one surrounding a "core" containing a DNA polymerase and a large-molecular-weight (70S) RNA possessing detectable homology to the RNAs of the mouse mammary tumor virus (MMTV) and of the Mason-Pfizer monkey virus (MPMV). We report here the purification and characterization of the DNA polymerase from the human breast cancer particles. Its key properties are very similar to those ofthe RNA-dependent DNA nucleotidyltransferase (reverse transcriptase) found in MMTV and MPMV. Thus like these viral enzymes, the purified human breast cancer DNA polymerase exhibits the following three features that together distinguish the known viral reverse transcriptases from normal cellular DNA polymerases: (i) a strong preference for oligo(dT)-poly(rA) over oligo(dT)-poly(dA) as a template for the synthesis of poly(dT); (ii) the acceptance of the highly specific oligo(dG)-poly(rCm) as a template for the formation of poly(dG); (iii) the ability to use a viral RNA (AMV) as a template to fashion a faithful DNA complementary copy; and (iv) its preference for Mg++ over Mn++. In summary, the data described here on the enzyme of the human breast cancer particles add further evidence of similarities to the viral agents associated with the corresponding malignancies in the mouse and monkey models. To date, an enzyme with these properties has not been detected in normal breast tissues or in benign tumors of the breast.
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PMID:Purification and characterization of the DNA polymerase of human breast cancer particles. 26 40

Specificity of TdT5 as a marker for ALL was evaluated by determining its activity in cells from normal control subjects and from 35 pediatric patients with ALL, AML, Hodgkin's disease and disseminated Burkitt's lymphoma. We evaluated the DNA polymerase activity, cell surface phenotypes (E rosettes, EAC rosettes, Smlg and la-like, HTLA and cALL antigens), and hematological and cytochemical characteristics in both the normal and patient groups. DNA polymerase alpha + beta and DNA polymerase gamma activity were indiscriminately high in all immature cells as found in ALL, AML, Burkitt's lymphoma and phytohemagglutinin-stimulated normal lymphocytes, when compared to mature leukocytes found in normal individuals or in patients whose cancer was in remission. High TdT activity was found in 24 of 26 T and non-T/non-B ALL patients in active phase as well as in two of three AML patients one of whom had Auer rods. Thus, TdT, although valuable for monitoring ALL patients, may have limitations in separating AML from ALL.
Int J Cancer 1978 Jul 15
PMID:High terminal deoxynucleotidyl transferase activity in pediatric patients with acute lymphocytic and acute myelocytic leukemias. 27 33


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