Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A ribonuclease that hydrolyzes either linear duplex or single-stranded RNA in an exonucleolytic manner has been partially purified from Ehrlich ascites tumor cell nucleoli and is free from other ribonucleases. The enzyme will also degrade the RNA complement of an RNA X DNA duplex; however, no nuclease activity is observed on linear duplex or single-stranded DNA. The exonuclease acts on RNA nonprocessively from the 3' end releasing 5'-mononucleotides. The enzyme has a broad pH optimum around pH 8.0, requires Mg2+ or Mn2+ (0.06 mM) for optimum activity, and is sensitive to ethylenediaminetetraacetic acid and N-ethylmaleimide inhibition. Monovalent cations including K+, Na+, and NH4+ are inhibitory. Gel filtration studies of this enzyme gave a Stokes radius of 40 A. Sedimentation velocity measurements in glycerol gradients yield a S20,W of 6.0 S. From these values a native molecular weight of 100 000 was calculated. Copurification of the single- and double-stranded activities, identical reaction requirements, and identical heat-inactivation curves strongly suggest that both activities reside with the same enzyme.
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PMID:Purification and properties of a novel nucleolar exoribonuclease capable of degrading both single-stranded and double-stranded RNA. 399 80

Two DNA polymerase with properties of viral RNA-directed DNA polymerase can be found in RIII mouse milk. One enzyme is the polymerase of type-C viruses; this enzyme prefers manganese to magnesium with poly(rA).oligo(dT) as synthetic template, is inhibited by specific sera, and has an apparent molecular weight of 70,000. Milk from BALB/c and NIH Swiss mice contain a vast predominance of this type-C enzyme. The other DNA polymerase from RIII mouse milk prefers magnesium to manganese, is not inhibited by type-C antipolymerase serum, and appears larger on gel chromatography than the type-C viral polymerase. Its presence in milk from RIII mice and absence from milk of mice with low content of mammary tumor virus correlates to the relative degree of type-B virus expression in these mice. The DNA polymerase of Mason-Pfizer monkey virus, isolated from a rhesus monkey breast tumor, also has a marked preference for magnesium with poly(rA).oligo(dT), is not immunologically related to primate type-C viruses, and appears larger than the gibbon type-C enzyme on gel chromatography.
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PMID:Characterization and separation of viral DNA polymerase in mouse milk. 412 83

RNA tumor viruses contain a characteristic RNA-dependent DNA polymerase (reverse transcriptase) which has been thought to be related to the induction of leukemia by this virus. A disturbance in a zinc-dependent enzyme system was first postulated to account for the demonstrated differences in zinc metabolism of normal and leukemic leukocytes [Vallee et al. in (1949) Acta Unio. Int. Contra Cancrum 6, 869 and (1950) Acta Unio. Int. Contra Cancrum 6, 1102]. In order to investigate the relationship between zinc and the initiation of leukemia in chickens by avian myeloblastosis virus, we have examined the metalloenzyme nature of its reverse transcriptase. The present data show that this protein is a zinc metalloenzyme demonstrating the postulated relationship between zinc and a leukemic process. Paucity of purified enzyme generated the design of a novel system of analysis incorporating microwave-induced emission spectrometry combined with gel exclusion chromatography. It provides precision, reproducibility, and remarkable limits of detection on mul samples containing 10(-12) to 10(-14) g-atoms of metal, and is thus orders of magnitude more sensitive than other methods. The chromatographic fraction with highest enzymatic activity contains 1.8 x 10(-11) g-atoms of zinc per 1.6 mug of protein, corresponding to either 1.8 or 2.0 g-atoms of zinc per mole of enzyme for a molecular weight previously determined either as 1.6 or 1.8 x 10(5). Copper, iron and manganese are absent, i.e., at or below the limits of detection, 10(-13) to 10(-14) g-atoms. Agents known to chelate zinc inhibit the enzyme, while their nonchelating isomers do not. The data underline the participation of zinc in nucleic acid metabolism and bear importantly upon the lesions that accompany leukemia and zinc deficiency.
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PMID:RNA-dependent DNA polymerase (reverse transcriptase) from avian myeloblastosis virus: a zinc metalloenzyme. 413 17

The RNA-dependent DNA polymerase(s) in murine leukemia, murine mammary tumor, and avian myeloblastosis viruses require maganese for optimal activity. The transcription of added synthetic polyribonucleotides is greatly enhanced when manganese is used in place of magnesium. A soluble RNA-dependent DNA polymerase activity has been released from murine leukemia particles in the presence of manganese and high detergent concentrations. Two RNA viruses, visna virus of sheep and a primate syncytial virus, not known to have tumor-producing ability, also contain the polymerase.
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PMID:RNA-dependent DNA polymerase activity in five RNA viruses: divalent cation requirements. 432 57

Feline leukemia virus DNA polymerase was purified by ion-exchange and nucleic acid affinity chromatographies. The enzyme consists of a single polypeptide chain of mol. wt. approx. 72,000 as determined by both glycerol density gradient centrifugation and SDS-polyacrylamide gel electrophoresis. The preferred divalent cation for DNA synthesis is Mn2+ on a variety of template-primers, and its optimum concentration appears to be significantly lower than reported results of other mammalian type-C viral enzymes. The purified enzyme also contained RNAase H activity. Both DNA polymerase and RNAase H activities appear to reside on the same molecule as demonstrated by the copurification of both activities through various purification steps. The divalent cation requirement for maximum activity of RNAase H is also similar to that of the DNA polymerase. RNAase H without detectable polymerase activity was generated by a limited chymotrypsin digestion of the purified reverse transcriptase. This RNAase H activity was inhibited equally effectively as RNAase H in the intact reverse transcriptase by antisera prepared against reverse transcriptase of feline leukemia virus. These results indicate that the RNAase H catalytic activity of reverse transcriptase is distinct from the polymerase portion of the molecule. Since the RNAase H activity appears to be more stable, the measurement of RNAase H activity with a proper antibody might be useful for assaying tumor cells for the presence of the viral enzyme.
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PMID:Biochemical and immunological properties of the DNA polymerase and RNAase H activities of purified feline leukemia virus reverse transcriptase. 615 69

Superoxide dismutase activity in virulent strains of Agrobacterium tumefaciens was found to be higher than that in avirulent strains. Polyacrylamide gel electrophoresis revealed two isoenzymes in both these strains. These isoenzymes are suggested to be iron and manganese containing superoxide dismutases. Crown gall tumor cells of the plant Bryophyllum calycinum were found to have higher superoxide dismutase activity than the normal plant cells. Polyacrylamide gel electrophoresis revealed two isoenzymes in both normal and crown gall tumor cells. Advantages of the higher superoxide dismutase activities in respect of the survival of virulent strains of A. tumefaciens and crown gall tumor growth have been discussed.
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PMID:Studies on superoxide dismutase activities in virulent and avirulent strains of Agrobacterium tumefaciens and also in normal and crown gall tumor cells of Bryophyllum calycinum. 618 36

The murine Leydig tumor cell line, MLTC-1, has specific cell surface receptors for human chorionic gonadotropin (hCG), which are coupled to adenylate cyclase. When the cells were exposed to hCG, there was a loss of these receptors (down-regulation), which was both dose- and time-dependent. Down-regulation was inhibited by lowering the temperature, removing bound hormone or blocking protein synthesis with cycloheximide. Down-regulation was found to be a biphasic event. The initial phase was dependent upon the binding of hormone and had a half-time of approximately 3 h. The second phase occurred around 8 h after exposing the cells to the hormone and was apparently independent of bound hCG. It was related to increases in cyclic AMP since it could be mimicked by incubating the cells with choleragen or dibutyryl cyclic AMP and isobutylmethylxanthine. The reappearance of hormone receptors began approximately 24-32 h after the initial exposure to hCG and was complete within 48 h. Adenylate cyclase activity in membranes from control and down-regulated cells responded equally well to Mn2+ and NaF indicating that neither the catalytic or regulatory component (G/F) of the adenylate cyclase system had been lost during downregulation. Cholate extracts of control and down-regulated cells also were equally effective at reconstituting isoproterenol-stimulated adenylate cyclase activity in S49 cyc-membranes (which lack a functional G/F). Thus, down-regulation did not impair the ability of G/F to couple receptors to the catalytic component of adenylate cyclase.
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PMID:Down-regulation of gonadotropin receptors in a murine Leydig tumor cell line. 619 55

Natural killer (NK) cell activity of mice given a single injection of manganese chloride (MnCl2) was significantly enhanced as measured in a 4-hr in vitro 51Cr release assay. Enhanced activity persisted for several days after injection. This cytotoxic activity was associated with nonadherent spleen cells and was completely eliminated by injecting MnCl2-treated mice with anti-asialo GM1 serum. Manganese-enhanced natural cytotoxicity was observed in several mouse strains with differing NK cell reactivity (CBA/J, C57BL/6, A/J, C3H/HeJ, and C57BL/6 beige mice) and with several tumor target cells with differing sensitivity to NK cytolysis (YAC-1, RBL-5, EL-4, and P815). The growth of B16-F10 melanoma lung tumors was inhibited in mice injected with MnCl2 one day before tumor challenge. Manganese chloride enhancement of NK cell activity appeared to be mediated by interferon (IFN). Low levels of IFN were detected in the serum of mice as early as 4 hr after MnCl2 injection. Rabbit anti-mouse IFN alpha, beta but not anti-mouse IFN gamma completely eliminated the MnCl2-enhanced NK cell activity in the spleens of mice. The observed enhancement of NK cell activity by MnCl2 is similar to that reported for more complex molecules that act by inducing IFN production.
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PMID:Manganese chloride enhances murine cell-mediated cytotoxicity: effects on natural killer cells. 620 61

Quercetin is a naturally occurring flavonoid, chemically related to cromolyn. Quercetin has been shown to inhibit antigen- and mitogen-induced histamine release from rat mast cells and basophils of subjects with hay fever, to increase cyclic adenosine monophosphate (AMP) in Ehrlich ascites tumor cells and to inhibit phosphodiesterase and certain adenosine triphosphatase (ATPase) systems. We have studied the effect of quercetin on mouse T cell responses. When 5 x 10(-6) to 5 x 10(-5) M quercetin is present throughout either allogeneic mixed leukocyte culture (MLC) or cytotoxic T lymphocyte (CTL) assay culture, inhibition of in vitro CTL generation or effector function results, respectively (inhibition is 75-100% at 2 x 10(-5) M and 100% at 5 x 10(-5) M). Quercetin also inhibits concanavalin A-induced DNA synthesis. Addition of Cu2+ strongly blocks the effects of quercetin in all systems tested, in a concentration dependent fashion, while Mg2+ and Ca2+ have little or no effect and Mn2+ and Co2+ have a significant but slight blocking effect on quercetin-mediated inhibition of both CTL generation and function. In kinetic studies, evidence was obtained for the existence of a major quercetin-sensitive step in CTL induction, between 3 and 24 hr of the MLC.
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PMID:Quercetin inhibition of the induction and function of cytotoxic T lymphocytes. 621 17

Burkitt's lymphoma cell line, P3HR-I, was found to secrete virions with properties of known type-C RNA tumor viruses. The viral particles had a buoyant density of 1.16 g/ml in sucrose gradients and contained a high-molecular-weight RNA and an RNA-instructed DNA polymerase. The viral polymerase was active in an endogenous reaction requiring the presence of the four deoxyriboside triphosphates and manganese ions, and was sensitive to RNase. The DNA product of the endogenous reaction specifically hybridized to P3HR-I viral 60 to 70S RNA. Electron microscopic examination of ultrathin sections of P3HR-I cells revealed immature, mature and budding virions typical of type-C retroviridae. Nucleic acid hybridization assays showed no sequence homoblastosis virus, murine oncornaviruses, simian sarcoma virus or RD114 virus.
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PMID:Evidence for type-C retrovirus production by Burkitt's lymphoma-derived cell line. 624 66


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