Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.25.1 (deoxyribonuclease)
 1,471 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytosol from human benign hyperplastic and carcinomatous prostatic tissue has been shown to contain a progestin receptor with a dissociation constant of approximately 10(-9) M. The receptor was measured using 3H-labeled R 5020 (17 alpha, 21-dimethyl-19-nor-4,9-pregnadiene-3,20-dione) as ligand. Progesterone, cyproterone acetate, and R 1881 (methyltrienolone) were efficient competitors to R 5020 for binding sites on the receptor whereas testosterone, 5 alpha--dihydrotestosterone, estradiol, cortisol, and several hydroxylated and saturated derivatives of progesterone did not compete. The [3H]R 2020-receptor-complex had a sedimentation coefficient of approximately 4 S, an isoelectric point of approximately 5, was heat-labile, and was destroyed by treatment with trypsin but not with deoxyribonuclease or ribonuclease. Seventeen of 21 patients with benign prostatic hyperplasia and three patients with prostatic carcinoma had 1 to 40 fmoles of specific R 5020-binding sites per mg of cytosol protein. One sample of normal prostatic tissue did not contain significant amounts of progesting receptor. Tissue specimens removed by transvesical adenoma enucleation displayed a larger number of specific R 5020-binding sites than electroresected specimens. The progestin receptor in hyperplastic prostate may be involved in the mechanism of the action of progestins used in the medical treatment of benign prostatic hyperplasia. Quantitation of progestin receptor in cancer of the prostate may form part of the basis of a predictive test program for endocrine therapy of prostatic malignancy.
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PMID:Demonstration of a progestin receptor in human benign prostatic hyperplasia and prostatic carcinoma. 7 18

The deoxyribonuclease activities from human lymphocytes have been compared with the activities from acute lymphocytic leukemic cells and mouse leukemic cells L5178Y using the in situ detection of deoxyribonucleases in DNA-containing polyacrylamide gels following their separation by micro-disc-electrophoresis. A neutral deoxyribonuclease activity is completely missing in leukemic cells of untreated patients while a group of acid deoxyribonuclease activities is increased. A similar deoxyribonuclease pattern can be seen in L5178Y cells. Under medical treatment the increment of the acid deoxyribonuclease activities disappears and the neutral deoxyribonuclease activity reappears.
Cancer Lett 1975 Nov
PMID:Deoxyribonucleases activities in human leukemic cells and mouse lymphoblasts. 107 Oct 14

It was shown that normal nonimmune C3H mouse spleen cells became specifically cytotoxic to chemically-induced syngeneic C3H tumor cells by incubation with xenogeneic I-RNA extracted from the lymphoid organs of specifically immunized guinea pigs. This response was specific for the tumor used to immunize the I-RNA donor. In a totally syngeneic system, we showed that syngeneic I-RNA extracted from the spleens of tumor-bearing rats mediated cytotoxic immune reactions which were directed specifically against the tumor-associated antigens of syngeneic rat tumor target cells. Active antitumor I-RNA synthesis in the lymphoid organs of I-RNA donor animals reached a maximum between days 14 and 21, depending on the route of administration and the nature of the immunizing tumor. Active I-RNA preparations were insensitive to treatment with deoxyribonuclease or pronase, but were inactivated by ribonuclease treatment; thereby indicating that the active moiety was one or more species of RNA. The active fractions of the I-RNA preparations had sedimentation values in sucrose density gradients of 12-16S, and comprised only a small fraction of the total RNA present in the lymphoid cells. Active antitumor I-RNA appeared to be localized in the cytoplasm of sensitized lymphoid cells, rather than in the nucleus. Lymphocytes from normal human donors as well as from cancer patients, when incubated with xenogeneic or allogeneic I-RNA, became specifically cytotoxic for human tumor cells in vitro. Crossreactivity among tumors of the same histologic type was observed, but not crossreactivity with tumors of other histologic types. Xenogeneic I-RNA extracted from the lymphoid organs of donor animals immunized either iwth tumor cells or normal tissues, following incubation with normal allogeneic lymphocytes, mediated cytotoxic immune reactions which were directed both against tumor-associated antigens and normal transplantation antigens. However, when autologous lymphocytes were used as effector cells, only immune reactions directed against tumor-associated antigens were observed. Allogeneic I-RNA extracted from peripheral blood lymphocytes of human cancer patients mediated specific cytotoxic immune reactions that were directed against common tumor-associated antigens shared by human tumors of similar histologic type. I-RNA's directed against "self" normal cell surface antigens appear to be recognized as self by lymphocytes, and immune responses against these self antigens are not elicited. On the other hand, I-RNA's directed against "nonself" tumor-associated antigens induce lymphocytes to effect specific antitumor immune responses. Our data are consistent with the hypothesis that I-RNA is an information-containing ribonucleic acid molecule capable of mediating immune reactions in vitro which are specific for the tumor-associated antigens of the tumor used to immunize the I-RNA donor.
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PMID:Mediation of immune responses to tumor antigens in vitro by immune RNA. 107 64

The recently isolated neutral deoxyribonuclease from crab (Cancer pagurus) testes has been characterized in its mode of action and its specificity. The enzyme is a typical endonuclease, forming 5'-phosphate oligonucleotides of large average size; after extensive digestion of calf thymus DNA over 75% of the fragments have a size larger than pentanucleotides and mononucleotides are absent. As far as specificity is concerned, thymidine is very abundant in the 5'-penultimate position (approximately 50%) and in the 3'-terminal position (37%) and almost absent in the 5'-terminal position (approximately 1%), the values quoted concerning Escherichia coli digests of average size (Pn) between 50 and 10.
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PMID:The specificity of a neutral deoxyribonuclease from Cancer pagurus. 123 41

UV exposure has been linked to skin cancer in humans by epidemiology and the rare genetic disease xeroderma pigmentosum. However, UV produces multiple photoproducts in DNA, and their relative contribution is uncertain. An enzyme which specifically repairs cyclobutane pyrimidine dimers in DNA, T4 endonuclease V, was encapsulated in liposomes for topical delivery into mouse and human skin. In both species, liposomes applied after UV exposure localized in the epidermis and stimulated the removal of cyclobutane pyrimidine dimers. UV-irradiated mice treated with these liposomes had a dose-dependent decrease in the incidence of squamous cell carcinoma compared to controls. The results demonstrate that unrepaired cyclobutane pyrimidine dimers in DNA are a direct cause of cancer in mammalian skin.
Cancer Res 1992 Aug 01
PMID:Pyrimidine dimer removal enhanced by DNA repair liposomes reduces the incidence of UV skin cancer in mice. 163 36

The open reading frames of the phosphoprotein pp58 (BMRFI) and the deoxyribonuclease (BGLF5) of the Epstein-Barr-virus (EBV) strain M-ABA were cloned in the baculovirus expression vectors pAc373 and pAc360 and expressed in the Spodoptera frugiperda (SF158) insect cells. The recombinant phosphoprotein pp58 expressed in SF158 cells was recognized by the anti-pp58 rabbit anti-sera which were generated by immunizing rabbits with a TrpE-BMRFI fusion protein expressed in E. coli. DNA-cellulose chromatography showed that the recombinant pp58 exhibited DNA-binding activities. Immunofluorescence, immunoblot and ELISA analysis indicated that sera from patients with nasopharyngeal carcinoma (NPC) contained antibodies against pp58. The recombinant EBV DNase expressed in SF158 cells was recognized by the anti-EBV DNase rabbit anti-sera which were generated by immunizing rabbits with a TrpE-C-terminal part of BGLF5 fusion protein expressed in E. coli. The anti-EBV DNase rabbit anti-sera recognized also a protein of about 52 kDa in the EBV-harboring human B-cell lines Raji, Jijoye, B95-8, M-ABA and BL74 induced by TPA and n-butyrate. The recombinant EBV DNase exhibited exonuclease and endonuclease activities, a requirement for magnesium, and a high pH optimum (8.0). Its enzyme activities could be inhibited by sera from NPC patients and anti-EBV DNase rabbit anti-sera. Comparable studies of Raji EBV-DNase and recombinant EBV-DNase implied that recombinant EBV-DNase could also be used in the enzyme activity assay for the detection of NPC. In contrast to the enzyme inhibition test, immunofluorescence and immunoblot analysis demonstrated that the recombinant EBV DNase exhibited only a weak immunological reaction with NPC sera.
Int J Cancer 1991 Jul 30
PMID:Immunological characterization of the Epstein-Barr virus phosphoprotein PP58 and deoxyribonuclease expressed in the baculovirus expression system. 165 Mar 30

Meta-iodobenzylguanidine (MIBG) is a guanidine analogue of the neurotransmitter norepinephrine. Radioiodinated [131I]MIBG is clinically used as a tumor-targeted radiopharmaceutical in the diagnosis and treatment of adrenergic tumors. Moreover, non-radiolabelled MIBG exerts several cell-biological effects, tentatively ascribed to interference with cellular mono(ADP-ribosyl) transferases (Smets, L.A., Bout, B. and Wisse, J. (1988) Cancer Chemother. Pharmacol. 21, 9-13; Smets, L.A., Metwally, E.A.G., Knol, E. and Martens, M. (1988) Leukemia Res. 12, 737-743). In the present study it was investigated whether MIBG could serve as an acceptor for the ribosyl transferase activity of cholera toxin and of erythrocyte membranes. MIBG appeared a substrate for the cholera toxin-catalyzed transfer of the ADP-ribose moiety of NAD to arginine-like residues with the highest affinity for this enzyme reported as yet (Km = 6.5 microM). MIBG was also ADP-ribosylated by the mono(ADP-ribosyl)transferase(s) of turkey erythrocyte membranes. Moreover, the drug appeared a potent affector of the ADP-ribose linkage to membrane proteins by these enzymes. Interference by MIBG was stronger than by related guanyltyramine, the monoamine precursors of MIBG, meta-iodobenzylamine had no effect at all. In contrast, the drug failed to affect endogenous, O-linked poly(ADP-ribose) polymerase, induced in nuclei of S49-leukemia cells by deoxyribonuclease. Since MIBG is the first described drug that specifically interferes with the cellular N-linked mono(ADP-ribosyl) transferase reactions, it may be an important tool to elucidate the physiological role of this posttranscriptional protein modification.
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PMID:Meta-iodobenzylguanidine (MIBG), a novel high-affinity substrate for cholera toxin that interferes with cellular mono(ADP-ribosylation). 210 58

It has been reported that deoxyribonuclease (DNAse) treatment does not destroy viral DNA, but it does digest native nuclear DNA. To determine what effect, if any, papillomavirus infection has on DNA ploidy values of genitourinary condylomas, DNA was measured with and without DNAse exposure in seven urethral condylomas, shown by prior in situ hybridization to contain abundant human papillomavirus types 6 and 11. Normal human skin was used as a negative control. Consecutive paraffin-embedded tissue sections were stained according to Feulgen before and after DNAse treatment. The DNA was measured by image analysis. In control tissue, DNAse obliterated DNA, and the Feulgen reaction was negative. In six of seven condylomas the DNA content was reduced, but a measurable Feulgen reaction was still present in isolated cells. In the seventh case there were no significant changes in the histograms. This observation strongly suggests that the presence of human papillomavirus has a significant effect on measurements of DNA ploidy in genital condylomas and, by implication, possibly also in other tissues containing the virus. Possible mechanisms are discussed.
Cancer 1990 May 15
PMID:Influence of human papillomavirus on DNA ploidy determination in genital condylomas. 216 Dec 79

Phosphorylation is a major post-translational regulatory mechanism and plays a key role in transduction of mitogenic signals in cell proliferation. The role of phosphorylation and dephosphorylation in regulating the activities of a multiprotein DNA polymerase alpha complex was examined. Treatment of the HeLa cell multiprotein DNA polymerase alpha with calf intestinal alkaline phosphatase resulted in the inactivation of DNA polymerase alpha and DNA primase but had no effect on deoxyribonuclease- and primer-recognition proteins. A protein kinase co-purified with the multiprotein DNA polymerase alpha and was partially purified from HeLa cells. The partially purified kinase was active in phosphorylating dephosphorylated polymerase alpha and used casein and histones as exogenous substrates. This study demonstrates that phosphorylation-dephosphorylation may have modulated the activities of DNA replicative enzymes and suggests a role for specific phosphatases and kinases in this process.
Cancer Commun 1989
PMID:Phosphorylation of HeLa cell multiprotein DNA polymerase alpha complex: impact on activity and partial purification of the associated kinase. 256 5

Multi-drug resistance (MDR) in cancer cells is associated with reduced drug accumulation. Although intensively studied, the mechanism of this process remains ill-defined. We have now developed a new, rapid and quantitative method of measuring uptake of doxorubicin by these cells, in which the fluorescence of accumulated drug is rapidly quenched by DNA in the cell nucleus. Pre-treatment of cells with deoxyribonuclease eliminates DNA from non-viable, permeable cells, and this obviates the spurious fluorescence quenching that made previous application of this technique useless. Our data strongly suggest that the drug passively diffuses into cells. The rate of this diffusion into drug-resistant cells is considerably lower than that found in drug-sensitive cells. The ratio of the rates of drug entry in these cell types could fully account for the differences between the cell lines in doxorubicin growth-inhibitory activity. In these experiments no evidence for the previously proposed active efflux mechanism was found in either cell line.
Int J Cancer 1989 Sep 15
PMID:Doxorubicin resistance in P388 leukemia--evidence for reduced drug influx. 277 17


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