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

In extracts of spleen tissue from two patients with haemotological malignancies an RNA dependent DNA polymerase was found in particles with a density of 1.16, that is at the density of oncorna viruses. After treatment with noniomic detergents the enzyme activity was found in particles with a density of 1.23-1.24, similar to the density of oncorna viral cores. A simultaneous detection test with this core fraction material for 70 S RNA and RNA dependent DNA polymerase was positive for both patients. Electron microscopical inspection of the material with a density of 1.16 revealed immature C-type virus like particles, various stages of maturing particles and a number of particles resembling mature C-type oncorna viruses. In two normal spleens from patients with carcinoma of the colon and oesophagus respectively and in three spleens from patients with no history of malignancy no RNA dependent DNA polymerase was found. Material from one normal spleen was examined in the electron microscope and no virus-like particles were seen.
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PMID:Biochemical and electron microscopical evidence for the presence of oncorna viruses in spleen tissue from two patients with haematological malignancies. 6 13

The activities of streptovaricin complexes, streptovaricins, streptovals, and streptovarinic degradation products were elevated against RNA-directed DNA polymerases of Rauscher leukemia virus, DNA-dependent DNA polymerase of bacterial and mammalian cells, and DNA-dependent RNA polymerases of mammalian origin. The activities of streptovaricins were also listed for comparison purposes. The effects of streptovaricin complexes on viral DNA polymerases varied significantly from lot to lot, and streptovaricin complex lot 7 was the most active. All the streptovals and streptovaricin degradation products except varicinal A showed a marked improvement (twofold to tenfold) in activity against the viral enzyme over the parent streptovaricins. None of these compounds, however, displayed any significant effect on either the DNA polymerase of L1210 leukemia cells and Escherichia coli or the RNA polymerase of isolated nuclei of mouse liver. As a result of tests in these systems, some specific inhibitors of RNA-directed DNA polymerases of Rauscher leukemia virus were selected.
J Natl Cancer Inst 1977 Feb
PMID:Effects of streptovaricins and their degradation products on RNA-directed DNA polymerase of Rauscher leukemia virus. 6 15

Mouse mammary tumor viruses (MMTV) from three different strains of mice have been used to establish productive infections in feline and mink cell lines. The virions that are released by these cells compete completely in a radioimmunoassay for the major virion surface glycoprotein of MMTV (gp52), thus demonstrating that antigenic determinants of gp52 are viral coded. Competitive molecular hybridization studies have shown that the 60 to 70 S RNA's of MMTV's propagated in feline cells contain all the nucleic acid sequences found in 60 to 70 S RNA from MMTV synthesized by murine cells. The virion buoyant densities in sucrose and cesium chloride, virion sedimentation coefficient, divalent cation requirement of the virion DNA polymerase, and morphology of MMTV's synthesized in heterologous cells are similar to those of MMTV's grown in murine cells. Cultures of MMTV-infected feline cells have continuously released between 0.1 and 1.0 microgram of virus per 10(7) cells (75-sq cm flask) per day during the 60-week observation period. No detectable feline or murine type C viruses were produced by these cultures.
Cancer Res 1977 Aug
PMID:Characterization of mouse mammary tumor viruses propagated in heterologous cells. 6 13

The cytoplasmic extracts of human prostatic tissues yield two classes of "particles" when centrifuged to equilibrium in a sucrose density gradient, one class banding at a density of 1.15-1.18 g/cm3 ("high density particles") and another at a density of 1.07-1.14 g/cm3 ("low density particles"). Both bands display endogenous DNA polymerase activity which is largely resistant to actinomycin D inhibition. The endogenous DNA products synthesized by high density particles give some indication of high molecular weight RNA:DNA complexes. The tissue extracts from normal, hyperplastic, and neoplastic prostate behave similarly in these assays. In addition, explant cultures of hyperplastic and neoplastic prostate either release, or can be induced to release, particles by treatment with bromodeoxyuridine. These particles band at a density of 1.15-1.18 g/cm3 in a sucrose density gradient and possess RNA and associated DNA polymerase activity which utilizes poly(A):oligo(dT). Our results suggest that human prostatic tissues may contain functions analogous in some ways to those of known RNA tumor viruses of other species.
Cancer Treat Rep
PMID:RNA tumor virus-like activities in human prostate: possible novel pharmacologic approaches. 6 16

Northern poke lymphosarcoma DNA polymerase was partially purified from particulate fractions banding at 1.15 to 1.16 g/ml from homogenates prepared from frozen necropsies of tumor-bearing pike. The enzyme behaves as a typical reverse transcriptase, in that it prefers ribotemplates to deoxytemplates. The isoelectric point (pl 5.5) is similar to that of avian myeloblastosis virus polymerase. The pike enzyme elutes from a phosphocellulose column at 0.22 M potassium phosphate, the same as avian myeloblastosis virus DNA polymerase. The enzyme activity is inhibited by pyran, a specific inhibitor of viral DNA polymerases. The most striking difference between the pike lymphoma polymerase and the other viral DNA polymerases tested is the low maximum temperature of 20 degrees, compared to 30 degrees for Rauscher leukemia virus polymerase and 38 degrees for avian myeloblastosis virus and Rous sarcoma virus.
Cancer Res 1977 Sep
PMID:Presence of DNA polymerase in lymphosarcoma in northern pike (Esox lucius). 6 92

Two unique cell lines, NALM-1 and BALM-2 derived from lymphoblast-like cells of chronic myelogenous leukemia and rare B cell acute lymphoblastic leukemia patients, respectively, were compared with fresh parent cells from the patients and with a Philadelphia chromosome positive K-562 cell line previously established from a chronic myelogenous leukemia patient in blastic phase. NALM-1 resembled the parent cells in the presence of Philadelphia chromosome, non-T/non-B acute lymphoblastic leukemia specific antigens and lack of T or B cell markers, whereas BALB-2, like the parent cells, had two chromosome markers and bore kappa, delta and mu immunoglobulins. NALM-1 lacked Epstein-Barr virus genome, whereas BALM-2 showed the presence of Epstein-Barr virus genome. K-562 cells lacked all the antigen markers examined. All cells had high DNA polymerase alpha activity and low DNA polymerase gamma activity. NALM-1, like the parent cells and unlike K-562 cells, had high terminal deoxynucleotidyl transferase activity of about 200 mu/mg DNA, whereas BALM-2, like its parent cells, had terminal deoxynucleotidyl transferase activity of 1-2 mu/mg DNA (1 u = 1 nmole Mn++-dGTP/h on dA12-18 initiator). Terminal deoxynucleotidyl transferase was characterized by its chromatographic and sedimentation behavior, thermal sensitivity and specific inhibition by streptolydigin and terminal deoxynucleotidyl transferase antisera. These results indicate that NALM-1 and K-562 may represent different phenotypes of cells in CML blastic crisis. Moreover, NALM-1 and BALM-2 seem to have retained the characteristics of original leukemic cells from which they may have been derived.
Int J Cancer 1977 Aug 15
PMID:Terminal deoxynucleotidyl transferase activity and cell surface antigens of two unique cell lines (NALM-1 and BALM-2) of human leukemic origin. 7 Apr 13

Particulate DNA polymerase activity that copied poly(2'-O-methylcytidylate) . oligodeoxyguanylate and banded at a density of 1.15 to 1.20 g/ml in sucrose gradients was detected in 8 of 16 human ovary tumors and in 11 of 16 malignant prostate tissues. None of the 10 nonmalignant ovary and prostate tissues examined contained detectable particulate DNA polymerase activity that copied poly(2'-O-methylcytidylate) . oligodeoxyguanylate. Since poly(2'-O-methylcytidylate) . oligodeoxyguanylate is effectively copied by oncornavirus RNA-directed DNA polymerase (reverse transcriptase) although not by the known species of human cell DNA polymerase, these results are interpreted as supporting the concept that some malignant human tissues contain particle-associated reverse transcriptase activity.
Cancer Res 1978 Apr
PMID:Detection in human ovary and prostate tumors of DNA polymerase activity that copies poly(2'-O-methylcytidylate) . oligodeoxyguanylate. 7 7

4'-(9-Acridinylamino)methanesulphon-m-anisidide (AMSA) (NSC 141549), an acridine derivative with activity against a variety of laboratory tumors in vivo, is presently undergoing Phase 1 clinical evaluation. The interaction of AMSA with DNA and its effects on nucleic acid-polymerizing enzymes were examined in an attempt to define the site of cytotoxicity of AMSA. Binding of AMSA to DNA, as demonstrated by equilibrium dialysis and spectrophotometric methods, appears to be similar to other aminoacridines, in that two types of binding sites (type 1 and type 2) were observed. Fluorescence studies and thermal denaturation studies gave strong evidence that AMSA type 1 binding was by intercalation into DNA. The binding of AMSA to DNA was without marked base-pair specificity. Furthermore, the effect of AMSA on nucleic acid-polymerizing enzyme activities (mouse embryo DNA polymerase alpha, avian myeloblastosis virus reverse transcriptase, and Escherichia coli RNA polymerase) was studied. Inhibition of enzyme activity by AMSA appeared to be independent of DNA base sequence. The relatively high concentrations of AMSA required for inhibition of these enzymes as compared to the concentrations of AMSA necessary for cytotoxicity in vitro suggest that the interaction with DNA alone might not fully explain its antitumor activity.
Cancer Res 1978 May
PMID:Interaction of 4'-(9-acridinylamino)methanesulfon-m-anisidide with DNA and inhibition of oncornavirus reverse transcriptase and cellular nucleic acid polymerases. 7 12

A phosphonoacetate (PA)-resistant mutant of the herpesvirus of turkeys (HVT) was isolated and characterized. The mutant of HVT resistant to PA (HVTpa) replicated in duck embryo fibroblast (DEF) culture in media containing 300 microgram PA/ml, whereas the replication of the wild type of HVT (HVTwt) was completely inhibited in DEF culture in media containing 100 microgram PA/ml. The HVTpa was distinct from the HVTwt in plaque morphology, but was indistinguishable antigenically and showed in vitro temperature sensitivity at 41 degrees C (3741 degrees C efficiency of replication was about 5). It replicated poorly in chickens and failed to provide complete protection against challenge with Marek's disease virus (MDV). The HVTpa-induced DNA polymerase had an apparent inhibition constant for PA, an apparent inhibition constant for pyrophosphate, and an apparent Michaells constant for dCTP about 10, 2, and 2.5 times, respectively, greater than the constants for the HVTwt-induced enzyme and was also more thermolabile.
J Natl Cancer Inst 1978 May
PMID:A phosphonoacetate-resistant mutant of herpesvirus of turkeys. 7 81

This report describes the use of equilibrium gradients, RNA dependent DNA polymerase assays and electron microscopy (EM) in a combined assay for the rapid preliminary detection of intact retroviruses in crude preparations. Positive combined assays of platelets from preleukemic patients corresponded with karyotypic abnormalities found in these patients. Reconstruction experiments with Rauscher Leukemia Virus added to buffer or disrupted mouse spleen demonstrated the ease of detecting 10(9) or greater particles/g crude tissue, and the effects of buffer or added protein.
Cancer Lett 1978 Mar
PMID:A combined assay for the rapid preliminary detection of structural retroviruses. 7 85


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