Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.31.1 (micrococcal nuclease)
 2,818 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

After administration of N-nitrosomorpholine (NNM) to female Wistar-rats the ribosomal RNA (18 S and 28S rRNA) of the livers contained "abnormal" dinucleotides which were resistant against treatment with alkali or with spleen phosphodiesterase. These and further observations are discussed in view of the hypothesis that during the induction of liver tumors a metabolite of NNM causes crosslinks of nucleic acid bases. The application of this hypothesis on the effects of NNM upon DNA permits to explain the additional results that have been obtained. Observations on NNM metabolism as reported in the literature are not inconsistent with this interpretation.
Z Krebsforsch Klin Onkol Cancer Res Clin Oncol 1975 Nov 25
PMID:[Nucleotide alterations of 18 S and 28 S ribosomal RNA from rat liver during carcinogenesis induced by N-nitrosomorpholine (author's transl)]. 17 5

Poly(adenosine diphosphate ribose) polymerase, a chromatin-bound enzyme, was stimulated 150 to 200% after treatment of HeLa cells with methylnitrosourea (MNU). In contrast, a slight inhibitory effect on enzyme activity was observed after treatment of cells with various concentrations of chloroethylnitrosoureas. To define precisely the differential effects of nitrosoureas on the enzyme activity, their interactions with chromatin substructure were studied. A nonrandom, in vivo alkylation of chromatin DNA by equimolar concentrations of MNU and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) was revealed by digestion of nuclei from drug-treated cells with micrococcal nuclease and DNase I. [methyl-14C]MNU interacted preferentially with the more accessible regions of chromatin, the internucleosome linkers, whereas, the [chloroethyl-14C]CCNU alkylated the nucleosomal core DNA to a greater extent. These two drugs also differed in their extent of covalent modification of histone and nonhistone chromosomal protein. The binding of MNU to histones was greater than of CCNU. CCNU mainly affected nonhistone proteins. This difference in the reactivity of methyl and chloroethyl nitrosoureas with chromatin may relate to their differential effect on poly(adenosine diphosphate ribose) polymerase activity, as well as to their carcinogenic and antitumor properties.
Cancer Res 1979 Apr
PMID:Nitrosourea interaction with chromatin and effect on poly(adenosine diphosphate ribose) polymerase activity. 21 35

A dialysable low-molecular-weight factor capable of affecting in vitro properties of macrophages was extracted from four different mouse tumors. This factor not only modulates closely related properties of peritoneal macrophages such as spreading and migration but also inhibits lipopolysaccharde-induced tumoricidal activity of these cells. It can be extracted not only from tumor tissues but also from tumor cells grown in vitro. The appearance of this factor is unique to tumors and it is not present in detectable quantities in normal tissues. The factor from one of the tumors, Lewis lung carcinoma, was purified extensively and the partially purified factor retains all the above effects on macrophages. It is not sensitive to pronase or a mixture of bovine spleen phosphodiesterase II, E. coli alkaline phosphatase and pancreatic ribonuclease. The factor is lipid-like in character and it is soluble in both organic solvents and aqueous media. It has ionizable group(s) and is anionic at neutral pH but non-ionic under acidic conditions.
Int J Cancer 1979 Mar 15
PMID:Characteristics of a low-molecular-weight factor extracted from mouse tumors that affects in vitro properties of macrophages. 22 Jan 97

As an approach to the mechanism of the nuclear translocation of estrogen receptor, the estradiol nuclear receptor (RN) of lamb endometrium was extracted with micrococcal nuclease at 2--4 degrees and compared to the "native" 8S and to the Ca2+-transformed cytosol receptors. After extensive digestion of chromatin, giving up to 10% perchloric acid-soluble DNA and a majority of nucleosome monomers, up to 80% of the RN was extracted and under low ionic strength. This RN was found to be completely different from the partially proteolyzed Ca2+-transformed cytosol receptor. It migrated with a sedimentation constant of 4 and 6 S. The Stokes radius of the predominant form as determined by ACA 34 chromatography was 5.3 nm. The calculated apparent molecular weights were 130,000 and 90,000, respectively. The RN was able to bind DNA and was eluted from a diethylaminoethyl cellulose column at 0.23 and 0.30 M KCl. We conclude that the mechanism proposed by Puca et al., according to which the Ca2+-transformed cytosol receptor is split by a Ca2+ receptor-transforming factor into a smaller form able to cross the nuclear membrane, is very unlikely.
Cancer Res 1978 Nov
PMID:Comparison between different forms of estrogen cytosol receptor and the nuclear receptor extracted by micrococcal nuclease. 69 61

In summary, operations in the FCRC pilot plant have included training an operating staff, operability trials, equipment modification and repair, and supplementation of the original equipment to gain greater versatility. In addition to effort spent on proving and improving the capacity of the pilot plant, development studies and production operations involving translation of laboratory operations to pilot level or volume have included: 1. Development of a production process for interferon as described above. As a by-product of the interferon program, samples of cell culture have been studied in the Basic Research Division of FCRC for the production of lymphokines. 2. Production of starting materials (cell paste) for carboxypeptidase G1, using three different organisms, and production of refined material from the FCRC 252 organism as described herein. 3. Production of large quantities of crude phenylalanine ammonia lyase in the form of cell paste for Prof. Creed Abell at the University of Texas, Medical Branch, at Galveston,. 4. Production of a crude staphylococcal nuclease for the program of Dr. David Sachs, National Cancer Institute, Bethesda, Maryland. 5. Developmental studies and limited production of a crude cysteine desulfhydrase according to the protocols of Dr. J. Uren, Sidney Farber Cancer Center, Boston, Massachusetts. 6. Preliminary production studies on the agent produced by Culture FCRC 14, discovered in the CFL search program. 7. Developmental fermentation studies on the antitumor antibiotic, piperazinedione 593A [6], in preparation for production of quantities of this antibiotic to support clinical studies under the auspices of the National Cancer Institute.
Recent Results Cancer Res 1978
PMID:Microbial process translation--laboratory to pilot plant at the Frederick Cancer Research Center. 70 17

This study compares the effects of in vitro modification of native duck reticulocyte DNA by [14C]-N-acetoxy-2-acetylaminofluorene in terms of alterations in DNA secondary structure, ability to reconstitute nucleosome structures in chromatin, and template activity for in vitro transcription. In contrast to the control native DNA, the carcinogen-modified DNA was susceptible to partial digestion by the single-strand-specific endonuclease S1. Depending on the particular conditions, for every [14C]-N-2-acetylaminofluorene residue released, about 5 to 35 base pairs of DNA were also released during the S1 nuclease digestion. Chromatin was reconstituted in vitro utilizing [14C]-N-2-acetylaminofluorene-modified DNA and unmodified chromatin-associated proteins. This reconstituted chromatin showed the same kinetics and extent of digestion by staphylococcal nuclease and similar nucleosome profiles on sucrose gradient density centrifugation as those obtained with native chromatin or chromatin reconstituted with unmodified DNA. The carcinogen-modified DNA and also chromatin reconstituted from this DNA showed, however, marked reductions in their abilities to serve as templates for transcription with Escherichia coli RNA polymerase. These results suggest that the covalent binding of N-2-acetylaminofluorene to DNA produces localized regions of denaturation in the DNA and that this is associated with a marked impairment in template activity during transcription. This modification, however, does not grossly affect the ability of the DNA to interact with chromosomal proteins to form apparently normal nucleosome structures.
Cancer Res 1977 Mar
PMID:Effect of N-2-acetylaminofluorene modification on the structure and template activity of DNA and reconstituted chromatin. 83 69

This investigation was designed to study whether methylation of liver chromatin DNA by dimethylnitrosamine (DMN) and the subsequent in vivo removal of DNA-bound methylated products are random. Liver chromatin DNA was fractionated into nuclease-digestible and nondigestible material 4 hr following the administration of [3H]DMN (0.5 mg/250 muCi/100 g body weight). Digestion of such methylated liver chromatin with pancreatic DNase I or micrococcal nuclease and analysis of nuclease-digested acid-soluble products revealed a discrepancy between the radioactivity released (72%) and the nucleotides released (50%) as measured by the absorbance at 260 nm. This discrepancy disappeared, and the rate and extent of release of both the radioactivity and the absorbance at 260 nm were identical when the total purified DNA isolated from methylated chromatin was used as the substrate instead of chromatin DNA in the nuclease reaction. These results, together with the fact that guanine contents of the DNA of the two fractions of the chromatin isolated by nuclease digestion were identical, suggest that methylation of the nuclease-accessible region of hepatic chromatin DNA is relatively greater than that of the inaccessible region. The study of the removal of methylated products in the accessible region of the chromatin DNA further reveals that, of the methylated products present at 4 hr, 62% is lost by 3 days, 87% is lost by 1 week and 94% is lost by 2 weeks. However, loss from the nuclease-inaccessible region of chromatin DNA is only 27% by 3 days, 49% by 1 week, and 86% by 2 weeks, thereby suggesting that the removal of methylated products from this region of chromatin DNA is relatively slower compared with that from the nuclease-accessible region of chromatin-DNA. The results of this study thus indicated (a) an increased methylation and faster rate of removal of DMN-induced methylated products in nuclease-accessible regions of chromatin DNA and (b) decreased methylation and slower rate of removal from the nuclease-inaccessible regions of chromatin DNA. It is concluded that the distribution and removal of DMN-induced methylated products in liver chromatin DNA is nonrandom as measured by this technique.
Cancer Res 1976 Jun
PMID:Nonrandom nature of in vivo methylation of dimethylnitrosamine and the subsequent removal of methylated products from rat liver chromatin DNA. 126 60

To improve our understanding of the mechanism of 1-beta-D-arabinofuranosylcytosine (ara-C) incorporation into DNA, we investigated the physical properties (size, position of nucleoside incorporation) of small fragments of nascent DNA (nDNA) obtained by pH-step alkaline elution of intact HL-60 cells following their exposure to ara-C. In the pH-step alkaline elution procedure, the smallest fragments of nDNA elute at pH 11. Anion-exchange high-performance liquid chromatography (HPLC) of nDNA obtained by 1 h elution at pH 11.0 of lysed HL-60 cells revealed a preponderance of nDNA fragments ranging from 0.5 to 40 kb in control ([3H]-dThd-labeled) cells. Exposure of cells to ara-C (0.8-1 microM) resulted in a loss of the preponderance of radiolabel in fragments of 0.5-40 kb along with redistribution of the radiolabel (from [3H]-dThd or [3H]-ara-C) into smaller nDNA fragments (predominantly < 100 bases in length) as determined by HPLC. We used the ability of pH-step alkaline elution to provide these small nDNA fragments produced by ara-C to investigate the paradoxical behavior of ara-C as a chain terminator in cell-free DNA synthetic systems while being incorporated into an internucleotide position in intact cells. Following the digestion of purified nDNA with micrococcal nuclease and spleen phosphodiesterase II, the proportion of radiolabel in 3'-dNMP (indicating an internucleotide position) or free nucleoside (indicating a chain terminus position) was determined by reverse-phase HPLC. In digests of prelabeled genomic DNA, as expected, > 90% of the radiolabel from [14C]-dThd or [3H]-ara-C was found to exist in an internucleotide position (as determined by co-chromatography with authentic 3'-dTMP or 3'-ara-CMP). In contrast, digests of nDNA that eluted at pH 11.0 revealed a significantly higher proportion of radiolabel in the chain terminus position (29%-35%) when the nDNA was obtained from cells exposed to 1 microM [3H]-ara-C as compared with cells exposed to [3H]-dThd or [3H]-dCyd alone (< 10%). These data obtained from pH-step alkaline elution of intact cells suggest that by causing the inhibition of chain elongation while failing to inhibit the formation of new nDNA replication intermediates, ara-C exposure leads to the production of very small nDNA fragments. This relative chain-terminating effect of ara-C is most apparent in the small nDNA replication fragments that elute at pH 11.0.(ABSTRACT TRUNCATED AT 400 WORDS)
Cancer Chemother Pharmacol 1992
PMID:Mechanistic implications of alterations in HL-60 cell nascent DNA after exposure to 1-beta-D-arabinofuranosylcytosine. 145 61

Previous studies have suggested that 1-(4-amino-2-methylpyrimidine-5-yl)-methyl-3-(2-chloroethyl) -3-nitrosoureahydrochloride (ACNU) and 1,(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) bind specifically to the nucleosomal DNA of murine bone marrow and L1210 leukaemia cells whereas the glucose nitrosoureas, 2-(3-(2-chloroethyl)-3-nitrosoureido)-2-deoxy-D-glucopyranose, (chlorozotocin, CLZ) and 1-(2-chloroethyl)-3-(-D-glucopyranosyl)-1-nitrosourea (GANU), bind preferentially to the linker DNA of bone marrow but not tumour cell chromatin. In order to provide an explanation for this differential, the DNA repeat and linker lengths in murine bone marrow and L1210 leukaemia cells were measured using electrophoresis of micrococcal nuclease-digested DNA. The linker length of bone marrow chromatin was approximately 22% longer than that in L1210 leukaemia cells from mouse ascites. The linker length of L1210 cells maintained in suspension culture was 27% less than in those from ascites fluid. The tissue-specific toxicity of sugar nitrosoureas and the differential binding of these drugs to chromatin does not appear to correlate quantitatively with differences in DNA linker length.
Br J Cancer 1985 Sep
PMID:DNA repeat length in chromatin from murine bone marrow and L1210 leukaemia cells. 293 Oct 97

Cultivation of Ehrlich-ascites tumor cells in the presence of N-mustard leads to a selection of cells with a defective choline carrier. As N-mustard employs the choline carrier for transport, this results in reduced drug uptake and in a decrease in drug sensitivity which is specific for N-mustard. Walker carcinoma cells with a stable pleiotropic resistance to a variety of alkylating agents and adriamycin exhibit no evidence for an impaired drug transport and show the same frequency of DNA-interstrand cross-links as the sensitive parental line. Both sensitive and resistant Walker cells exhibit equal capacities for repair of N-mustard induced DNA-interstrand cross-links. The inhibition of histone acetylation by N-mustard, however, was found to be significantly lower in the resistant Walker or Ehrlich cells compared to sensitive counterparts. Although the difference between N-mustard concentrations leading to half maximal inhibition of histone acetylation in sensitive and resistant cells is considerably smaller than the difference between N-mustard doses required for half maximal inhibition of cell proliferation the data suggest that--besides DNA-DNA cross-linking--the inhibition of histone acetylation has to be considered as an important alternative mechanism responsible for the cytotoxic activity of alkylating agents. Inhibition of histone acetylation is not due an accelerated deacetylation and is predominantly expressed in chromatin fractions soluble in 0.1 M NaCl after digestion with micrococcal nuclease.
Eur J Cancer Clin Oncol 1988 Dec
PMID:Differential sensitivity of histone acetylation in nitrogen-mustard sensitive and resistant cells. Relation to drug uptake, formation and repair of DNA-interstrand cross-links. 322 83


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