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)

Four DNA-dependent RNA-polymerases were separated from the cell homogenate of moust leukemia L1210 cell by DEAE-cellulose column chromatography and tentatively designated as Peaks I, II, III and IV in the elution order. Peak II was inactivated by the addition of alpha-amanitin and effects of antibiotics and enzymes on the RNA-polymerase activity using Peaks, I, II and a mixture of Peaks I and II were examined. The RNA-polymerases were used to screen for enzyme inhibitors produced by microbes. This enzymatic method was successfully proved to select antitumor antibiotics.
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PMID:On RNA-polymerases of leukemia L 1210 origin and an enzymatic method to screen antitumor antibiotics. 1 29

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 RNA-dependent DNA polymerase present in intracisternal A-type particles from mouse myeloma tumor cells has been studied. This polymerase can use either endogenous A particle RNA or an exogenous synthetic polynucleotide [poly (rA)] as a template. The DNA reaction product is small (4S-10S) and over 90% of it hybridizes to A particle RNA, whereas up to 50% of it hybridizes to murine sarcoma-leukemia virus RNAs. The RNA isolated from purified A particles is generally of low molecular weight (5S-15S) but contains small amount of 70S and 35S components. These results suggest that A-type particles may be related to C-type oncornaviruses.
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PMID:Characterization of DNA polymerase and RNA associated with A-type particles from murine myeloma cells. 4 84

Two RNase H (RNA-DNA hybrid ribonucleotidohydrolase, EC 3.1.4.34) activities separable by Sephadex G-100 gel filtration were identified in lysates of Moloney murine sarcoma-leukemia virus (MSV). The larger enzyme, which we have called RNase H-I, represented about 10% of the RNase H activity in the virion. RNase H-I (i) copurified with RNA-directed DNA polymerase from the virus, (ii) had a sedimentation coefficient of 4.4S (corresponds to an apparent mol wt of 70,000), (iii) required Mn-2+ (2 mM optimum) for activity with a [3-h]poly(A)-poly(dT) substrate, (iv) eluted from phosphocellulose at 0.2 M KC1, and (v) degraded [3-H]poly(A)-poly(dT) and [3-H]poly(C)-poly(dG) at approximately equal rates. The smaller enzyme, designated RNase H-II, which represented the majority of the RNase H activity in the virus preparation, was shown to be different since it (i) had no detectable, associated DNA polymerase activity, (ii) had a sedmimentation coefficient of 2.6S (corresponds to an apparent mol wt of 30,000), (iii) preferred Mg-2+ (10 to 15 mM optimum) over Mn-2+ (5 to 10 mM optimum) 2.5-fold for the degradation of [3-H]poly(A)-poly(dT), and (iv) degraded [3-H]poly(A)-poly(dT) 6 and 60 times faster than [3-H]poly(C)-poly(dG) in the presence of Mn-2+ and Mg-2+, respectively. Moloney MSV DNA polymerase (RNase H-I), purified by Sephadex G-100 gel filtration followed by phosphocellulose, poly(A)-oligo(dT)-cellulose, and DEAE-cellulose chromatography, transcribed heteropolymeric regions of avian myeloblastosis virus 70S RNA at a rate comparable to avian myeloblastosis virus DNA polymerase purified by the same procedure.
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PMID:Purification and characterization of the DNA polymerase and RNase H activities in Moloney murine sarcoma-leukemia virus. 4 24

DNA polymerase was purified from a cloned isolate of Moloney murine leukemia virus (M-MuLV). Purified M-MuLV DNA polymerase, upon analysis by polyacrylamide gel electrophoresis, showed one major polypeptide of mol wt 80,000. Estimation of molecular weight from the sedimentation rate of the purifed enzyme in a glycerol gradient was consistent with a structure containing one polypeptide. M-MuLV DNA polymerase could transcribe ribopolymers, deoxyribopolymers, and heteropolymers as efficiently as did purified DNA polymerase from avian myeloblastosis virus (AMV). M-MuLV DNA polymerase, however, transcribed native 70S viral RNA less efficiently than did AMV DNA polymerase. Addition of oligo(dT) enhanced five to tenfold the transcription of 70S viral RNA by M-MuLV DNA polymerase. Purified enzyme also exhibited nuclease activity (RNase H) that selectively degraded the RNA moiety of the RNA-DNA hybrid. It did not degrade single-stranded RNA, single-stranded DNA, double-stranded RNA, and double-stranded DNA. M-MuLV DNA polymerase-associated RNase H acted as a random exonuclease. When [3-H]poly(A)-poly(dT) was used as a substrate, the size of the M-MuLV DNA polymerase-associated RHase H digested product was larger than the size of the digestion products by AMV DNA polymerase. The oligonucleotide digestion products could be further digested to 5'-AMP by snake venom phosphodiesterase, indicating that the products were terminated by 3'-OH groups. Alkaline hydrolysis of the oligonucleotide digestion products generated pAp, suggesting that M-MuLV DNA polymerase-associated RNase H cleaves at the 3' side of the 3',5'-phosphodiester bond. The ratios of the rates of DNA polymerase activity and RNase H activity were not significantly different in the murine and avian enzymes.
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PMID:Studies on reverse transcriptase of RNA tumor viruses III. Properties of purified Moloney murine leukemia virus DNA polymerase and associated RNase H. 4 25

Dexamethasone (1,4-pregnadiene-9-fluor-16alpha-methyl-11beta,17alpha,21-triol-3,20-dione), a potent synthetic glucocorticoid, stimulates mouse mammary tumor virus expression 10- to 20-fold in tissue culture cells. This hormone effect was observed at concentrations as low as 1 times 10-10 M and was maximal at 10-7 to 10-8 M. The time course of induction indicated that detectable increases in extracellular viral DNA polymerase were first noted 18 to 24 hours following the addition of dexamethasone, and cells produced the highest polymerase levels at the time monolayers approached confluence. Steroid responsiveness was associated with specific increases in type B murine mammary tumor virus structural polypeptide (gp52(sl) expression and murine mammary tumor virus RNA that quantitatively paralleled the increase in extracellular virus production as measured by electron microscopy and supernatant RNA-dependent DNA polymerase activity. Another virally transformed murine cell line, KA 31, did not contain detectable levels of murine mammary tumor virus gp52(sl) or RNA before or after dexamethasone stimulation; thus induction was noted only in murine cells with pre-existing murine mammary tumor virus expression. No increase in basal levels of type C murine leukemia viral proteins or RNA was detected in dexamethasone-treated mammary cell lines which were producing increased levels of murine mammary tumor virus. Therefore, increases in murine mammary tumor virus gene products are specific for murine mammary tumor virus DNA sequences under these conditions.
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PMID:Mammary tumor virus induction by glucocorticoids. Characterization of specific transcriptional regulation. 4 26

Morphologic, tissue culture, immunologic, and biochemical methods have been used in an attempt to detect and characterize oncogenic viruses or their subviral components in cells derived from human prostatic carcinoma (PrCa) or benign prostatic hyperplasia (BPH). Electron microscopy was used to characterize the ultrastructural features of normal and neoplastic prostatic tissue. Examination of specimens of prostatic tissue from 34 patients with PrCa, ten patients with BPH, and three patients with bladder tumor (BT) revealed the presence of particles resembling type-C virus in three cases of PrCa and structures resembling budding type-C virus particles in one case of BPH. Fifty human prostatic tissue specimens have been set in tissue culture, of which 30 have been successfully grown for varying periods of time. Of 20 currently active cultures, nine consist primarily of epithelial cells. Immunofluorescence and mixed hemadsorption tests of cells derived from benign and malignant prostatic tissue and sera derived from patients with PrCa, BPH, BT, and other types of tumors, and from normal donors revealed that sera from patients with PrCa, BPH, or BT contain antibodies to antigens in cells derived from PrCa, BPH, or BT. The nature of these antigen-antibody reactions is under study. Initial biochemical studies have not detected reverse transcriptase in the tissue culture fluid from a small number of sparsely growing PrCa cultures nor specific gene sequences homologous to murine leukemia virus-Rauscher genomic RNA in preparations of either normal or malignant prostatic cell DNA. The results of these preliminary studies have demonstrated the applicability of the techniques employed to the study of the relationship of viruses to human PrCa and have provided a number of promising leads for further investigation.
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PMID:Virologic and immunologic studies of human prostatic carcinoma. 4 14

A molecular hybridization technique has been used to quantitatively measure the nucleotide sequence relationships of selected mammalian RNA tumor viruses. Reciprocal cross-hybridization tests were done in which a given radioactively labeled, viral genomic RNA species was annealed with an excess of unlabeled, complementary DNA product synthesized in endogenously instructed reverse transcriptase reactions. Hybrid formation was measured with pancreatic RNase A. Three representative mammalian RNA tumor virus groups were examined: murine viruses, simian viruses, and feline viruses. The results of reciprocal cross-hybridization testing have revealed that the murine viruses consist of four distinctly related subgroups: (i) the Friend leukemia virus/Rauscher leukemia virus subgroup, (ii) the Gross leukemia virus subgroup, (iii) the Moloney sarcoma virus subgroup, and (iv) the Kirsten sarcoma virus subgroup. Simian sarcoma virus, the only simian virus examined, appeared to share limited interspecies sequence relationships with members of the other virus groups and in particular with Kirsten sarcoma virus. Of the two members of the feline virus group tested, Rickard feline sarcoma virus and RD-114, each was placed in a separate, unrelated subgroup. Rickard feline sarcoma virus exhibited limited sequence relatedness with members of the other virus groups, whereas RD-114 exhibited none.
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PMID:Quantitative nucleotide sequence relationships of mammalian RNA tumor viruses. 4 42

The therapeutic activity of the narcissus residual alkaloid A-2 against Rauscher leukemia has been compared with 10 standard anticancer drugs, and synergistic or additive combination pairs have been selected using a viral leukemia and two transplantable tumor systems. An increased beneficial effect has been demonstrated by a combination of the alkylating and DNA-binding agents and the alkaloid against the three malignant tumors, while a beneficial effect by combining the alkaloid and the antimetabolites (either 6-MP or 5-azacytidine) was seen only against the viral leukemia. The alkaloid has no suppressive activity against cellular immunity as tested by PHA reactivity and allogeneic tumor rejection systems.
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PMID:Combination chemotherapy of Rauscher leukemia and ascites tumors by narcissus alkaloid with standard drugs and effect on cellular immunity. 4 97

Inhibition of DNA polymerase from oncorna viruses by a new class of macromolecular inhibitors is reported. The macromolecule, designated as mercaptopolycytidylic acid (MPC), is a chemically modified polycytidylic acid containing 5-SH cytidylic bases in the polymerase. Partially thiolated polycytidylic acids (MPC I-III, containing 1.7%, 3.5%, and 8.6% 5-mercaptocytidylate units, respectively) inhibited the DNA-polymerase of Friend leukemia virus (FVL) in the endogenic reaction as well as in the presence of poly rA-(dT)14 or poly (dA-dT) templates; the inhibitory activities were directly related to the percent of tholation. In a bacterial DNA polymerase (E coli-K12 with denatured calf thymus DNA as template) MPCI-III showed no activity. Biological experiments showed that MPC III inhibits the leukemogenic potential of cell-free spleen extracts from FVL-infected mice to about 60%, measured on the basis of spleen weight. The enzymatic and animal experiments have led us to carry out preliminary clinical trials in some cases of Children leukemia. These cases, resistent to the known therapeutic regimes (combination chemotherapy), responded well when treated with MPC along, or in combination with poly I. The experiments indicate that the development of modified polynucleotids with structural similarities to functional templates may be of potential use in the future chemotherapy of leukemia.
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PMID:[Inhibition of viral reverse transcriptase and leukemogenesis by modified nucleic acids (author's transl)]. 4 86


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