Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.22.1 (DNase II)
 429 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To provide information on the role of nucleases in oncogenic virus infection, the activities of 3'-nucleotide phosphodiesterase (3'-NPDase), 5'-nucleotide phosphodiesterase (5'-NPDase), acid deoxyribonuclease (DNase II), and 3',5'-cyclic AMP phosphodiesterase (cAMPDase) in spleen extracts of murine sarcoma virus-infected C57BL/6 inbred mice were studied. At the peak of tumor growth and of the cell-mediated cytotoxic response (CMC) against tumor-associated antigens, 3'-NPDase, 5'-NPDase, and DNase II all showed depressed activities in the spleen, whereas the activity of cAMPDase in the spleen increased at the peak of CMC and remained elevated thereafter. Serum enzyme activities of the infected mice were also determined, and only 3'-NPD-ase in serum correlated well with CMC. Inasmuch as the correlation of the tumor growth with CMC was established in this system, further study on tumors with variance between CMC and growth is necessary to determine if serum 3'-NPDase is a useful biochemical marker for CMC in vivo.
J Natl Cancer Inst 1978 Oct
PMID:Nucleases and adenosine 3',5'-cyclic monophosphate phosphodiesterase activities in murine sarcoma virus (Moloney)-infected mice. 21 66

Recent interest in the use of adriamycin-DNA complex as an approach to improve the therapeutic effectiveness and to reduce toxicity of adriamycin for cancer chemotherapy requires an in-depth understanding of the physicochemical and biochemical properties of such complexes. The interactions of adriamycin with single-strand polydeoxyribonucleotides, double-strand DNA, and double-strand ribodeoxyribopolynucleotide hybrids were therfore investigated. Association constants (Kapp) of adriamycin and polynucleotides were obtained. These data showed that the inherent variable in such complex lies in the composition of the polynucleotides. Alternate deoxyguanylate (dG)-deoxycytidylate (dC) sequence binds 7-fold better than alternate deoxyadenylate (dA)-deoxythymidylate (dT) sequence. Comparative studies of the hydrolysis of DNA duplexes by deoxyribonucleases I and II with and without adriamycin were also carried out. The rate of hydrolysis decreased in the order poly(dA-dT) greater than calf thymus DNA greater than poly(dG-dC) greater than poly(dA)-poly(dT) greater than poly(dG)-poly(dC) for DNase I and poly(dA)-dT) greater than calf thymus DNA greater than poly(dG-dC) greater than poly(dA)-poly(dT) greater than poly(dG)-poly(dC) for DNase II. Intercalation of adriamycin to deoxyribopolynucleotide duplex resulted in inhibition of DNase II two to three times more than tat of DNase I. On the other hand, intercalation of adriamycin to homodeoxypolynucleotide duplex poly(dA)-poly(dT) and poly(dG)-poly(dC) enhanced the DNase I hydrolysis. If DNase I activity could be related to serum DNase and DNase II related to tumor lyososomal DNase as in the endocytosis mechanism proposed by Trouet et al. (Cancer Chemotherapy Rept., 59: 260, 1975), the best adriamycin carrier suggested by this investigation could be poly(dA)-poly(dT) and poly(dG-dC). It is also suggested in this study that adriamycin-RNA-DNA hybrid could be of interest as an antiviral agent by a similar release mechanism via RNase H, an enzyme associated with viral reverse transcriptase.
Cancer Res 1976 Sep
PMID:Effect of deoxyribonuclease on adriamycin-polynucleotide complexes. 97 96

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

DNA- and RNA-concentrations, as well as in vitro activities of DNase I (EC 3.1.4.5), DNase II (EC 3.1.4.6), and DNase I inhibitor, have been determined in 63 spontaneous (man) and 22 experimentally induced (rat) nervous system blastomas of various types and of different degrees of malignancy. Generally, a distinct elevation of DNA concentrations and of the ratio (Q) of DNase II- to DNase I-activities has been observed when compared with control values. A statistically significant relationship could be demonstrated between increase of DNA concentrations and Q in experimentally induced neurinomas of rats as well as in human astrocytomas and glioblastomas. Whereas the increase of Q may be a biochemical expression of elevated DNA synthesis of tumour cells, no conclusions can be drawn as to the role of DNases in the process of malignant transformation.
 ...
PMID:[Deoxyribonucleases in spontaneous and experimental tumors of the nervous system]. 118 37

Nuclear localization of nerve growth factor (NGF) in HS 294 melanoma cells and SW 707 colorectal carcinoma was determined by indirect immunofluorescence staining and by cell fractionation. NGF receptors were immunoprecipitated from the EcoRI-digested chromatin of HS 294 melanoma cells, of melanocytes proliferating in the presence of 12-O-tetradecanoylphorbol-13-acetate, and of SW 707 colorectal carcinoma cells, using a monoclonal antibody to the Mr 75,000 cell surface NGF receptor. Melanoma cells expressed a receptor species with a molecular weight of 230,000. Proliferating melanocytes expressed a small amount of Mr 230,000 receptor, whereas colorectal carcinoma cells expressed a Mr 35,000 receptor. Scatchard analysis indicated one type of NGF chromatin binding site in HS 294 cells with KD = 241 pM but two types of binding sites in chromatin of SW 707 cells with KD = 333 and 1718 pM, respectively. Both the Mr 230,000 and the 35,000 receptor species were tightly bound to DNase II-sensitive regions, which became DNase II-insensitive after nerve growth factor binding. [125I]NGF was detected in the chromatin in nondegraded form. Chromatin binding of NGF inhibited RNA synthesis and cell proliferation.
Cancer Res 1988 Dec 15
PMID:Nerve growth factor receptors in chromatin of melanoma cells, proliferating melanocytes, and colorectal carcinoma cells in vitro. 246 Dec 54

Forty-seven human leukaemia/lymphoma cell lines belonging to myelocytic, monocytic, non-T/non-B, T-, and B-lineage and representing different levels of maturation as well as fresh cells from normal and leukaemic subjects were examined for immunological markers and cytochemically for acid phosphatase, alkaline phosphatase, alpha-naphthyl acetate esterase (pH 5.8 and 8.0), alpha-naphthyl butyrate esterase (pH 5.8 and 8.0), non-specific esterase, chloroacetate esterase, chymotrypsin-like protease, deoxyribonuclease II, beta-glucuronidase, sudan black, and periodic acid Schiff's staining. Strong sudan black, nonspecific esterase, and chloroacetate esterase reaction was obtained only for myelocytic and monocytic cell lines with the reaction intensity increasing progressively in more mature cells. Focal acid phosphatase reaction like T-ALL was found in all T-ALL cell lines, whereas myeloid/monocytoid lines had semicircular distribution and B-cell lines cytoplasmic distribution of activity. Acid phosphatase activity appeared to decline with maturation along both myeloid and T-cell lineage. High activity of alpha-naphthyl acetate esterase and alpha-naphthyl butyrate esterase both at pH 5.8 and 8.0 and of beta-glucuronidase was found in myeloid/monocytoid lines although both B- and T-cell lines in contrast to peripheral blood B-cells also had significant esterase activity. alpha-Naphthyl butyrate esterase activity declined with increasing cell maturation along myeloid lineage. Except for weak activity in two B-cell lines alkaline phosphatase was not detected in any cell lines. Monocyte esterase activity was inhibited by sodium fluoride whereas acid phosphatase, only from hairy cell leukaemia line, was resistant to L-tartarate. Although periodic acid Schiff's staining could not distinguish myeloid, T-, B-, or non-T/non-B cell lines it gave characteristic reaction (large number of coarse granules against a clear background forming a ring around the nucleus) with erythroblastic leukaemia cell line and along myeloid series its intensity increased in more mature cells. Deoxyribonuclease II and chymotrypsin-like protease staining were not discriminatory. The results of this study show that cytochemical staining characteristics of various leukaemia/lymphoma cell lines are comparable to those of corresponding cells from patients and that the intensity and pattern of expression of these activities are related to cell type and degree of cell maturation. These studies give further credence to the use of these cell lines in cell differentiation, differential drug cytotoxicity, and many other studies.
Br J Cancer 1983 Jun
PMID:Cytochemical comparison of immunologically characterized human leukaemia/lymphoma cell lines representing different levels of maturation. 619 Apr 91

The initial binding of N-fluorenylacetamide (2-FAA) and its N-hydroxy metabolite N-hydroxyl-N-2-fluorenylacetamide (N-OH-2-FAA) within the hepatic genome and the effect of ingestion of a 2-FAA-containing (0.05% wt/wt) diet on this binding were examined in the male noninbred Sprague-Dawley rat. Ingestion of 2-FAA for 2 weeks reduced the amount of newly bound carcinogen up to 80%. The extent of this decrease was significantly greater in rats treated with a single injection of 2-FAA when compared to one of N-OH-2-FAA. The distribution of carcinogen within the genome was measured after fractionation of chromatin by DNase II digestion followed by selective MgCl2 precipitation. Two hours after a single injection of N-OH-2-FAA, the amount of carcinogen bound per milligram DNA in the presumed template-active chromatin fraction was 16 times that bound to DNA of the presumed template-repressed chromatin fraction. The amount bound to DNA in the nuclease-resistant chromatin was equal to that observed in the DNA of the presumed template-active fraction. Most (85%) of the total bound carcinogen was located on less than 25% of the total DNA. Evaluation of the amount of carcinogen bound to the N-2 or C-8 positions of guanine demonstrated a significant inverse correlation between the amount bound to a DNA fragment and the percent of that binding occurring at the N-2 position. DNA of the repressed chromatin fraction had the largest N-2/C-8 ratio when compared to the ratios seen in both the expressed chromatin and the nuclease-resistant chromatin DNA. Pretreatment of rats with 2-FAA when compared to one of N-OH-2-FAA. The distribution of carcinogen within the genome was measured after fractionation of 66:667-672.
J Natl Cancer Inst 1981 Apr
PMID:Factors influencing the binding of N-2-fluorenylacetamide to specific regions of the hepatic genome in vivo in rats. 693 14

The levels of Acid and Alkaline DNases were measured in the serum of patients with: (a) Cancer of the Genitourinary Tract (confirmed by biopsy), (b) with inflammatory diseases and non-malignant tumours of the Genitourinary tract, (c) healthy blood donors. In the first group the results showed that the Acid DNase level was raised in 62% and Alkaline DNase in 43%. In the second group acid DNase was increased in 30% and Alkaline DNase in 13%. In the third group Acid and Alkaline DNase levels were normal. These results suggest that the measurement of Acid and Alkaline DNases could be considered as malignant diseases markers, in spite of false positive and false negative results in some cases.
 ...
PMID:The role of acid and alkaline DNases as tumour markers in cancer of the genitourinary tract. 711 81

The effects of steroid-induced modifications of chromatin structure on the extent and sites of chloroethylnitrosourea binding to chromatin were studied using log-phase HeLa cells. The cells were exposed to 0.1 to 2.0 microM hydrocortisone for 22 hr; this resulted in depressed DNA synthesis while transcriptional activity was stimulated. Hydrocortisone had no effect upon cellular or nuclear uptake of the two nitrosoureas under study, 0.6 mM chlorozotocin or 1-(2-chloroethyl-3-cyclohexyl-1-nitrosourea). Both drugs were found to alkylate transcriptional chromatin preferentially, as demonstrated by DNase II and DNase I digestion. This alkylation was stimulated 2-fold by the same micromolar concentrations of hydrocortisone, 0.1 to 2.0 microM, which stimulated transcription. The extent of nuclear RNA alkylation, determined using RNase T2 as a probe, was found to contribute less than 20% of total chromatin alkylation and was unaffected by steroid pretreatment. Instead, the increased alkylation within these chromatin subfractions was attributed to a steroid-induced alteration of chromatin structure. Electron microscopic examination of HeLa nuclear morphology revealed a hydrocortisone-induced disaggregation of nuclear membrane-associated heterochromatin resulting in a more heterogeneous, less condensed distribution of chromatin. Such data are consistent with a relaxation of the supercoiled chromatin structure, resulting in increased transcription and increased accessibility of potential target sites for nitrosourea alkylation.
Cancer Res 1980 Oct
PMID:Influence of hydrocortisone on the binding of nitrosoureas to nuclear chromatin subfractions. 743 52

Apoptosis is a pathway of cell death characterized by internucleosomal digestion of genomic DNA. Such DNA digestion can be induced by both physiological stimuli and cytotoxic treatment with many anticancer agents. This digestion has generally been considered to be mediated by a Ca2+/Mg(2+)-dependent endonuclease that is activated by increases in intracellular Ca2+. However, we suggest that an alternate endonuclease, DNase II, may be a more likely candidate. In these studies, apoptosis was induced in human HL-60 cells by a 30-min incubation with the topoisomerase II inhibitor etoposide. DNA digestion characteristic of apoptosis began within 3 h of removal of etoposide. Morphological indication of apoptosis was observed concurrently. Only about 20% of the cells underwent apoptosis at this time; these appeared to be cells in S phase at the time of etoposide treatment. The remainder of the cells progressed to the G2 phase and arrested there for at least 48 h. Intracellular Ca2+ and pH were measured in individual cells by flow cytometry. No changes in intracellular Ca2+ were observed, but an acidification of up to 1 pH unit occurred in about 15% of the cells and correlated with the time course of appearance of DNA digestion. Cells were sorted on the basis of intracellular pH and only the acidic cells showed the morphology and DNA digestion characteristic of apoptosis. These results demonstrate the involvement of DNase II in apoptotic DNA digestion and suggest mechanisms of pH homeostasis as regulators of apoptosis.
Cancer Res 1993 May 15
PMID:Etoposide-induced apoptosis in human HL-60 cells is associated with intracellular acidification. 838 92


1 2 Next >>