Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have studied the unintegrated infectious DNA of Harvey sarcoma virus (Ha-SV) and Moloney leukemia virus (Mo-MuLV). The source of infectious viral DNA was the Hirt supernatant fraction from cells acutely infected with Ha-SV and Mo-MuLV. To obtain a direct quantitative assay for infectious viral DNA, recipient mouse cells were first exposed to calcium phosphate-precipitated viral DNA and then treated with dimethyl sulfoxide. Infectivity was monitored by focus formation for Ha-SV and XC plaque formation for Mo-MuLV. The viral DNA titration pattern followed single-hit kinetics for both foci and plaques, indicating that a single molecule carried information for each function. Focus-forming and plaque-forming activity were present in different molecules, since these two biological activities could be separated from each other by agarose gel electrophoresis. The focus-forming molecule was linear DNA with a molecular weight of about 4 x 10(6) daltons. The focus-forming activity of the viral DNA was sensitive to EcoRI and resistant to XhoI restriction endonucleases, whereas the plaque-forming activity was resistant to EcoRI and sensitive to XhoI. The generation of helper-independent foci indicates that Ha-SV DNA can transform mouse cells in the absence of helper virus or its proteins.
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PMID:Helper-independent transformation by unintegrated Harvey sarcoma virus DNA. 2 10

The alpha beta DNA polymerase of avian myeloblastosis virus was treated with dimethyl sulfoxide to dissociate the enzyme subunits. The dimethyl sulfoxide treated enzymes were passed over phosphocellulose to purify and characterize the dissociated subunits as well as to remove the dimethyl sulfoxide. RNA-directed DNA polymerase, RNase H, and nucleic acid-binding activity were monitored, as well as the subunit structure (on sodium dodecyl sulfate-polyacrylamide gels) of the various enzyme species obtained. With 30% dimethyl sulfoxide, the majority of DNA polymerase and RNase H activities as well as the alpha subunit were displaced from the alpha beta DNA polymerase position on phosphocellulose (0.23 M potassium phosphate) to the alpha DNA polymerase position (0.1 M). The association of DNA polymerase and RNase H activities with the alpha subunit suggests that alpha is the enzymatically active subunit in alpha beta. In addition to alpha DNA polymerase, a minor polymerase species eluted from phosphocellulose at 0.4 M potassium phosphate. The dissociated beta subunit eluted from phosphocellulose at a wide range of salt concentrations (0.28 to 0.5 M potassium phosphate). The dissociated beta subunit bound 3H-labeled murine leukemia virus RNA and [3H]poly(dT)-poly(dA) approximately 20-fold more avidly than alpha DNA polymerase alone. In contrast to the results with the alpha subunit, there was no correlation between DNA polymerase and RNase H activity profiles and the elution profile of the beta subunit from phosphocellulose. These observations suggest the beta subunit is either enzymatically inactive or possesses limited DNA polymerase and RNase H activity when compared with the alpha subunit.
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PMID:Dissociation of alpha beta DNA polymerase of avian myeloblastosis virus by dimethyl sulfoxide. 5 61

Rauscher leukemia virus RNA-directed DNA polymerase has been purified to near homogeneity (greater than 90% pure) using affinity chromatography on polycytidylate-agarose with over 85% recovery of input enzymatic activity. The purified enzyme has a molecular weight of approximately 70,000 and appears to consist of a single polypeptide chain. The enzyme is free of DNase, but has RNase H activity. Analysis of the requirements for optimal rates of DNA synthesis by this enzyme using synthetic and natural template-primers has revealed template-specific variations in such requirements. During these studies it was observed that DNA synthesis catalyzed by Rauscher leukemia virus DNA polymerase is inhibited by the addition of inorganic phosphate. An analysis of the mechanism of phosphate inhibition was carried out using the synthetic template-primer poly(A)-(dT)10. It appears that by some mechanism, possibly involving the substrate binding site of the enzyme, phosphate ions inhibit DNA synthesis with a more acute effect on the rate of chain growth than on that of initiation. The extension of these studies to DNA synthesis catalyzed by a variety of mammalian type C viral reverse transcriptases revealed that low levels ( less than or equal to 2 mM) of inorganic phosphate strongly inhibited DNA synthesis. The susceptibility to phosphate inhibition appears unique to mammalian type C viral enzymes since the type B viral enzyme, Escherichia coli DNA polymerase I, avian myeloblastosis virus and Mason Pfizer monkey tumor virus reverse transcriptase and cellular DNA polymerases alpha and gamma are not inhibited by inorganic phosphate. This phenomenon of phosphate inhibition of various DNA polymerases, therefore, provides a new basis for the differentiation of the sources and nature of these enzymes.
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PMID:Purification and properties of Rauscher leukemia virus DNA polymerase and selective inhibition of mammalian viral reverse transcriptase by inorganic phosphate. 6 68

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.
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PMID:Presence of DNA polymerase in lymphosarcoma in northern pike (Esox lucius). 6 92

We have studied the virus produced by a clone, termed 8A, that was isolated from a culture of murine sarcoma virus-transformed mouse cells after superinfection with Moloney murine leukemia virus (MuLV-M). Clone 8A produced high levels of type C virus particles, but only a low titer of infectious murine sarcoma virus and almost no infectious MuLV. When fresh cultures of mouse cells were infected with undiluted clone 8A culture fluids, they released no detectable pogeny virus for several weeks after infection. Fully infectious MuLV was then produced in these cultures. This virus was indistinguishable from MuLV-M by nucleic acid hybridization tests and in its insensitivity to Fv-1 restriction. It also induced thymic lymphomas in BALB/c mice. To explain these results, we propose that cone 8A is infected with a replication-defective variant of MuLV-M. Particles produced by clone 8A, containing this defective genome, can establish an infection in fresh cells but cannot produce progency virus at detectable levels. Several weeks after infection, the defect in the viral genome is corrected by back-mutation or by recombination with endogenous viral genomes, resulting in the formation of fully infectious progeny MuLV. The progeny MuLV'S that arose in two different experiments were found to be genetically different from each other. This is consistent with the hypothesis that, in each experiment, the progeny virus is formed clone 8A cells and assayed for infectivity by the calcium phosphate transfection technique. No detectable MuLV was produced by cells treated with this DNA. This finding, along with positive results obtained in control experiments, indicates that clone 8A cells do not contain a normal MuLV provirus.
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PMID:A replication-defective variant of Moloney murine leukemia virus. I. Biological characterization. 7 21

The biochemical properties of DNA polymerase purified from Mason-Pfizer monkey virus were studied, with respect to synthetic and natural template-primer utilization. Thes studies revealed the following new information about the Mason-Pfizer monkey virus enzyme: (a) Mason-Pfizer monkey virus polymerase was found to prefer template: primer molar nucleotide ratios of 2.5-5: 1 for optimal rates of synthesis with poly(C) .(dG)12-18 as template-primer. (b) Poly(A)-directed synthesis was stimulated by the addition of low concentrations of inorganic phosphate to the reaction mixture. (c) Poly(2' -O-methyl-cytidylate), poly(rCm), was the only template studied for which Mn2+ proved the preferred divalent cation. Combinations of divalent cations stimulated rather than inhibited poly(rCm)-directed poly(dG) synthesis by the Mason-Pfizer monkey virus enzyme. (d) Heteropolymeric regions of rabbit globin mRNA and avian myeloblastosis virus 70 S RNA could be copied by the Mason-Pfizer monkey virus polymerase with oligo(dT), oligo(U) or in the case of avian myeloblastosis virus RNA, endogenous primers. In all such studies, Mg2+ was the preferred divalent cation and a distinct preference for the DNA primer in the reverse transcription of natural RNAs was observed. These new findings necessitated comparative studies with the DNA polymerases from Rauscher murine leukemia virus and murine mammary tumor virus, as representative type C and type B retroviruses. Although the Mason-Pfizer monkey virus enzyme was found to share some properties in common with both type C and type B mammalian viral enzymes, certain of the above properties rendered it unique among the polymerases examined.
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PMID:Template-specific requirements for DNA synthesis by the Mason-Pfizer monkey virus DNA polymerase: unique aspects. 7 24

Bone marrow from normal BALB/c mice, mice with myeloid leukemia induced by Soule myeloid leukemia virus, and mice with virally induced mammary carcinoma was cultured in semisolid agar. Bone marrow from either leukemic or mammary tumor-bearing mice produces more clones in vitro in the presence of a specific colony-stimulating factor. However, in all cases, the myeloid progenitor cells have similar requirements for the colony-stimulating factor. The optimum condition for growth in all instances is 7% fetal calf serum + 7% horse serum + 7% tryptose phosphate broth. Decrease in the concentration of these three constituents has a less drastic effect on in vitro proliferation of bone marrow cells from leukemic mice. Some cells from Soule virus-induced leukemias even grew in the absence of serum. The combination of suboptimal amounts of serum and colony-stimulating factor is used as a tool for detecting cells with altered growth characteristics in bone marrow of leukemic mice. During the progression of the leukemia, there is an increase in the amount of transformed colony-forming cells per 5 X 10(4) bone marrow cells. The increase is already noticeable 4 weeks after inoculation, when no clinical signs of the leukemia are present, and reaches a maximum of about 20%.
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PMID:In vitro growth characteristics of virally transformed murine myeloid cells. 17 4

The synthesis and isolation of two derivatives of 2-amino-1,3,4-thialdiazole(aminothiadiazole) are described. The derivatives are a nicotinamide adenine dinucleotide (NAD) analog prepared by an exchange reaction with NAD in the presence of nicotineamide adenine dinucleotide glycohydrolase and a presumed aminothiadiazole mononucleotide prepared by treatment of the NAD analog with nucleotide pyrophosphatase. Both derivatives are potent inhibitors of inosine 5'-phosphate (IMP) dehydrogenase obtained from leukemia L1210 cells. The NAD analog is a pseudoir-reversible inhibitor of the enzyme, noncompetitive with either IMP or NAD. The aminothiadiazole mononucleotide has a K1 of about 0.1 muM, is competitive with IMP, and is uncompetitive with NAD: the inhibition appears to be reversible by Ackermann-Potter analysis. A metabolite of [5-14C]aminothiadiazole is formed in L1210 cells in vivo to a level of 0.3 nmole/10(9) cells. Retention volume of the metabolite on a high-pressure liquid chromatography system is the same as that of the aminothiadiazole mononucleotide prepared as described above. These results suggest that IMP dehydrogenase is the site of action for aminothiadiazole metabolites as was indicated by earlier observations. There is no evidence that the NAD analog is formed in vivo. Nicotinamide prevented formation of the mononucleotide in vivo. Therefore, since formation and cleavage of the NAD analog apparently are not the route to the thiadiazole nucleotide, some other pathway for the metabolism of nicotinamide may be involved such as the action of a phosphoribosyltransferase or the sequential action of a nucleoside phosphorylase and a nucleoside kinase.
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PMID:Mechanism of action of 2-amino-1,3,4-thiadiazole (NSC 4728). 18 32

Experimental evidence for the presence and biosynthesis of subviral, leukemogenic particles in the isolated mitochondria of spleen cells of mice infected with Rauscher murine leukemia (RML) virus is presented. These subviral particles sediment at a density of 1.27-1.29 g/ml and induce splenomegaly and RML three weeks after i.v. or i.p. administration to white mice. Virosomes have been labelled with [32P]phosphate in the isolated mitochondria from RML spleen cells and high molecular weight (70S) [32P]RNA has been isolated from these subviral, leukemogenic particles. Rauscher virus group specific antigens were detected by immunodiffusion in the inner membrane and matrix fraction of the mitochondria of RML spleen cells. These results together with our earlier findings strongly suggest that mitochondria of the transformed cells participate in the biosynthesis of RNA tumor viruses. Possible mechanism of the penetration of viral genetic information of RNA tumor viruses into mitochondria of tumor cells in vivo is discussed.
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PMID:Biosynthesis of subviral oncogenic particles (virosomes) in mitochondria of Rous sarcoma and Rauscher murine leukemia cells. 19 96

Uridine kinase, the rate-limiting enzyme in the activation (phosphorylation) of uridine and the corresponding chemotherapeutic analogues, is present as two isoenzymes localized exclusively in the cytosol of rapidly growing neoplasms, including the S-37 sarcoma, EL-4 leukaemia, HeLa cells (a human carcinoma) and the Novikoff hepatoma. The activities of the isolated isoenzymes are markedly decreased when the concentrations of ATP, phosphate or Mg2+ that are optimum in vitro are replaced by concentrations of ATP, phosphate or Mg2+ that are optimum in vitro are replaced by concentrations approximating to those found in vivo. Further, comparisons of the Km values of isolated uridine kinases with those for cellular uptake of pyrimidine nucleosides and their rate of intracellular phosphorylation suggest that nucleoside-transport systems play a rate-limiting role in nucleoside analogue activation and consequently that it is impossible to estimate the Km of uridine kinase in the intact cell. During the development of tumour-cell resistance to 5-fluorouracil or 5-fluorouridine in vivo there was an early differential increase in the activity of a low-affinity (high-Km) uridine kinase isoenzyme, as measured in cell extracts, and a 7-fold increase in the Km values for the uptake of both uridine and 5-fluorouridine into the intact resistant cells.
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PMID:Uridine kinase activities and pyrimidine nucleoside phosphorylation in fluoropyrimidine-sensitive and -resistant cell lines of the Novikoff hepatoma. 19 85


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