Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The induction of mutants at the hypoxanthine-guanine phosphoribosyltransferase and Na+/K+ ATPase loci by photoaddition of two bifunctional psoralens was compared in normal and in Fanconi's anemia lymphoblasts from the genetic complementation group A. For the two loci, the frequency of mutants was significantly lower in Fanconi's anemia than in normal cells. This is true whether the data are expressed as a function of dose or as a function of survival level. It is suggested that the chromosomal instability characteristic of Fanconi's anemia is responsible for the cancer proneness rather than the mutability at the gene level.
Cancer Res 1990 Jun 01
PMID:Mutagenic response of Fanconi's anemia cells from a defined complementation group after treatment with photoactivated bifunctional psoralens. 215 78

Merocyanine 540 (MC 540) is a photosensitizing dye that is used clinically for the purging of autologous bone marrow grafts and preclinically for the inactivation of enveloped viruses in blood products. Its mechanism of action is not yet well understood. This paper investigates the sites of MC 540-mediated photodamages in L1210 leukemia cells by examining the effects of MC 540-sensitized photoirradiation on several soluble and membrane-bound marker enzymes. When exposed to MC 540 and white light under a standard set of conditions, the activities of Na+/K(+)-ATPase, Mg2(+)-ATPase, and 5'-nucleotidase (three plasma membrane-bound enzymes) were reduced by 54, 49, and 55%, respectively. None of the intracellular enzymes included in this survey was affected by MC 540-sensitized photoirradiation as long as the plasma membrane remained intact. The two soluble enzymes, lactate dehydrogenase and malate dehydrogenase, remained refractory to MC 540-sensitized photoirradiation even after the plasma membrane had been disrupted. By contrast, the activities of the membrane-bound enzymes, NADPH-cytochrome c reductase and succinate dehydrogenase, were reduced in cell lysates by 55 and 81%, respectively. Purified NADPH-cytochrome c reductase was about 3 times less sensitive than the microsomal enzyme, suggesting that the membrane environment facilitated photoinactivation. The MC 540-sensitized photoinactivation of enzymes was accelerated in the presence of deuterium oxide and inhibited if oxygen in the medium was displaced by nitrogen or azide was added to the medium. Taken together, these data support the view that the plasma membrane is a major target of MC 540-mediated photodamages, that the inactivation of membrane-bound enzymes is an oxidative process, and that at least some photodynamic damages are mediated by type II chemistry.
Cancer Res 1990 Dec 15
PMID:Merocyanine 540-sensitized photoinactivation of soluble and membrane-bound enzymes in L1210 leukemia cells. 217 31

Immortalisation of human fibroblasts by transfection with a plasmid, pSV3neo, results in an increase in their radioresistance. The change in radiosensitivity may either be a consequence of transformation or due to expression of the SV40 T-antigen in pSV3neo. To investigate these two possibilities, we transfected pSV3neo into cells already transformed and immortalised. The radiosensitivities of three human bladder cancer cell lines were unaltered in clones expressing T-antigen, indicating that the changes observed in fibroblasts probably are a consequence of transformation, and not the presence of SV40 T-antigen.
Cancer Lett 1990 Dec 03
PMID:pSV3neo transfection and radiosensitivity of human cancer cell lines. 217 29

Human and murine cells can express anticancer activity which we define as any biologic process that can prevent or inhibit the expression of the transformed phenotype. The existence of anticancer activities has been demonstrated by many systems, including the fusion of normal cells with tumorigenic cells and the implantation of cancer cells into specific embryonic sites. Furthermore, cellular differentiation has recently been shown to regulate the expression of anticancer activity without limiting a cell's proliferative potential. Those results show that reversible nonterminal differentiation (NTD) induces 3T3T mesenchymal stem cells to become resistant to transformation by physical or chemical carcinogens or oncogene products and NTD induces spontaneously transformed 3T3T cells to revert to a benign state and to become resistant to retransformation. In addition, NTD induces SV40 T-antigen transformed 3T3T cells to revert to a nontransformed state that prevents growth in soft agarose. Data are now presented that define the relative stability of these differentiation-induced anticancer activities. Anticancer activity induced by NTD in 3T3T cells is shown to have a mean stability of 55 population doublings (PD) and a maximum stability of 88 PD. Anticancer activity induced by NTD in spontaneously transformed 3T3T cells shows a similar stability with a mean of 55 PD and a maximum of 95 PD. Finally, in SV40-3T3T cells, the induction of NTD suppresses soft agarose growth for a maximum of 20-30 PD. These results demonstrate that three forms of differentiation-induced anticancer activity are stable for an extended number of population doublings.
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PMID:Stability of anticancer activity induced by cellular differentiation. 230 32

Some cell surface membrane properties of tumors may depend upon the host tissue site. Therefore, local tumors and lung metastases were excised from athymic (nude) mice injected subcutaneously with LM fibroblasts. The excised local tumors and lung metastases were cultured in chemically-defined, serum-free medium to characterize their plasma membrane properties without complicating factors such as site of growth, presence of host inflammatory cells, and variation in nutrition. Plasma membranes were isolated from the cultured local tumor cells and cultured metastatic cells. The specific activities of (N+,K+)-ATPase and 5'-nucleotidase were elevated and decreased, respectively, in plasma membranes from metastatic cells as compared to local tumor cells, a finding consistent with data from directly excised local tumors and lung metastases. Plasma membranes of metastatic cells had a lower ratio of sterol/phospholipid, higher ratio of phosphatidylcholine/phosphatidylethanolamine, and no differences in phospholipid unsaturated/saturated fatty acid ratio compared to plasma membranes from the locally-derived tumor cells. Plasma membranes of metastatic cells were more fluid (lower limiting anisotropy) than those of local tumor cells as indicated by multifrequency phase and modulation fluorometry and the fluorescence probe molecule, 1,6-diphenyl-1,3,5-hexatriene. Thus, the higher fluidity of metastatic as compared to local tumor plasma membranes was not due to differences in site of growth, host cell contamination, and/or nutrition.
Cancer Lett 1990 Apr 09
PMID:Plasma membrane properties of cultured local LM cell tumors and metastases from athymic (nude) mice. 232 24

We found that rhabdomyosarcoma (RMS) subcellular membranes contain sialyltransferase activities for LcOse4Cer and GgOse4Cer acceptors. Chromatographic analyses and neuraminidase lability of the sialyltransferase products indicated that the principal site of sialylation was the non-reducing terminal galactosyl moiety. In order to control for the effects of cell density in culture, metastatic S4T18 RMS cells and nonmetastatic F9-4/21 RMS cells were harvested at 2 X 10(4) to 6 X 10(4) per cm2 prior to analyses. Irrespective of metastatic potential, we found that sialyltransferase-specific activities were influenced by cell densities. F9-4/21 cells, for example, at a density of 6 X 10(4), produced membranes with sialyltransferase-specific activities to LcOse4Cer 1.9-fold higher than cells at 2.1 X 10(4)/cm2. Metastatic potential (predetermined in vivo) appeared to be correlated with an accelerated effect of cell density on the sialyltransferase activity to LcOse4Cer. Metastatic S4T18 cells at 6.3 X 10(4)/cm2 yielded membranes with sialyltransferase-specific activities 5.4-fold higher than membranes from cells at 1.9 X 10(4)/cm2. Conversely, fucosyltransferase activities in the presence of LcOse4Cer were highest in non-metastatic F9-4/21 cells at low cell densities. Quantitative analyses of monosialoganglioside fractions of RMS cells were in agreement with the sialyl-transferase studies. HPLC and HPTLC analyses demonstrated the presence of glucosamine-containing monosialoganglioside with Rf identical with the radioactive products of LcOse4Cer sialylation, which increased 4.5-fold on a per mg protein basis as cell densities increased in S4T18 cells in culture from 1.9 X 10(4)/cm2 to 6.3 X 10(4)/cm2. Plasma membrane marker Na+, K+, ATPase-specific activity also increased in RMS metastatic cells in a manner comparable to that described for the sialyl-transferase activity to LcOse4Cer. Our results suggest that metastatic potential is expressed in the rate of sialylation at specific membrane sites of RMS intercellular contact. We propose a process of selection for metastasis whereby specific cell surface non-reducing galactosyl termini are recognized by intercellular transferases and lectins in the primary tumor, and the corresponding labile sialylated sites (on disseminated cells) are recognized by host neuraminidases.
Int J Cancer 1990 May 15
PMID:Monosialoganglioside biosynthesis by subcellular membranes of rhabdomyosarcoma cell lines differing in metastatic potential. 233

Adult Oryzias latipes were exposed to 50 mg of diethylnitrosamine per liter of water for 5 wk and then transferred to clean water for an additional 15 wk. Response of the liver during the first 6 wk were analyzed by enzyme histochemistry and by high-resolution light and transmission electron microscopy. After 1 wk, cytotoxicity was apparent at the light microscopic level by piecemeal necrosis and phagocytosis apoptosis by adjacent hepatocytes and resident macrophages. Spongiosis hepatis and inflammation, found as early as wk 3, were not widespread until wk 6. Glycogen depletion and multifocal increases in gamma-glutamyl transpeptidase were found as early as 3 wk. At 5 wk, macrophage infiltration and aggregation and hepatocyte lysosome proliferation were revealed by an increase in cells staining for acid phosphatase. In addition, a subpopulation of macrophages stained positively for glucose-6-phosphate dehydrogenase during wk 6. Other histochemical biomarkers (Mg2(+)-ATPase, DT-diaphorase, uridine diphosphoglucuronyl dehydrogenase) were not altered. Mitotic figures were rare for the entire 6-wk period. At the ultrastructural level, necrotic alterations of some hepatocytes were seen within 24 h. Within 48 h, an apparent reduction of hepatocyte glycogen and cell volume characterized the majority of hepatocytes; this was accompanied by an increase in interhepatocytic space and the length and complexity of the hepatocyte microvillous projections found in the space of Disse. Lipid vacuolar inclusions inhabited space previously occupied by glycogen. Margins of hepatocyte nuclei were irregular, and mitochondria were condensed and their shape altered so that crescentric and elongated profiles were abundant. Lysosomes and residual bodies were increased after 1 wk. The cytoplasmic processes delineating spongiotic lesions were identified as originating from Ito cells. After 4 wk, apparent proliferation of smooth endoplasmic reticulum and retention of transport lipid within its cisternae were seen. The toxic depletion of hepatocytes and the attendant altered cellular environment are discussed in relation to cell-to-cell interactions and the possible contribution of stromal and extracellular matrix changes to liver regeneration and neoplasia.
Cancer Res 1990 Sep 01
PMID:Cytotoxicity phase of diethylnitrosamine-induced hepatic neoplasia in medaka. 238 55

A number of closely related post-transcriptional facets of RNA metabolism show nuclear compartmentation, including capping, methylation, splicing reactions, and packaging in ribonucleoprotein particles (RNP). These nuclear 'processing' events are followed by the translocation of the finished product across the nuclear envelope. Due to the inherent complexity of these interrelated events, in vitro systems have been designed to examine the processes separately, particularly so with regard to translocation. A few studies have utilized nuclear transplantation/microinjection techniques and specialized systems to show that RNA transport occurs as a regulated phenomenon. While isolated nuclei swell in aqueous media and dramatic loss of nuclear protein is associated with this swelling, loss of RNA is not substantial, and most studies on RNA translocation have employed isolated nuclei. The quantity of RNA transported from isolated nuclei is related to hydrolysis of high-energy phosphate bonds in nucleotide additives. The RNA is released predominantly in RNP: messenger-like RNA is released in RNP which have buoyant density and polypeptide composition similar to cytoplasmic messenger RNP, but which have distinctly different composition from those in heterogeneous nuclear RNP. Mature 18 and 28S ribosomal RNA is released in 40 and 60S RNP which represent mature ribosomal subunits. RNA transport proceeds with characteristics of an energy-requiring process, and proceeds independently of the presence or state of fluidity of nuclear membranes. The energy for transport appears to be utilized by a nucleoside triphosphatase (NTPase) which is distributed mainly within heterochromatin at the peripheral lamina. Photoaffinity labeling has identified the pertinent NTPase as a 46 kD polypeptide which is associated with nuclear envelope and matrix preparations. The NTPase does not appear to be modulated via direct phosphorylation or to reflect kinase-phosphatase activities. A large number of additives (including RNA and insulin) produce parallel effects upon RNA transport and nuclear envelope NTPase, strengthening the correlative relationship between these activities. Of particular interest has been the finding that carcinogens induce specific, long-lasting increases in nuclear envelope (and matrix) NTPase; this derangement may underlie the alterations in RNA transport associated with cancer and carcinogenesis.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Nucleocytoplasmic RNA transport. 241 44

A combined histologic, immunohistologic, enzyme histochemical, and immunologic study has been carried out in a 7-year-old girl with recurring extramediastinal monocentric giant lymph node hyperplasia of hyaline-vascular type. A large panel of monoclonal and polyclonal antibodies to lymphoid and nonlymphoid cell markers were tested on frozen and paraffin-embedded lymph node tissue as well as on cell suspension and peripheral blood. Tissue enzyme histochemical study, including a conventional hematologic panel, was performed on frozen and plastic-embedded sections. The pattern was dominated by nodular aggregates of round BA-1+ Leu-14+ HLA-DR+ ATPase+ lymphocytes with polyclonal sIgD and sIgM positivity and lacking cIg and BA-2 staining. Leu-1+/Leu-4+, OKT6+, OKT10+, Leu-7+, and CALLA+ cells were few or absent in the nodules, whereas DRC-1+ BA-2+ HLA-DR+ 5'-Nuc+ cells formed a dendritic network in the outer portion of the nodules. No immunoreactivity for lymphoid and nonlymphoid cell markers, including cytokeratin and keratin, was detected in centrinodular histiocytic-like cells. Particularly, the Hassall's-like structures contained a target-like positivity for laminin, and consisted of flattened acid phosphatase (AP), alpha-naphthyl acetate esterase (ANAE), 5'-nucleotidase (5'-Nuc), and adenosine triphosphatase (ATPase) positive cells, whose enzyme profile overlapped with that of the histiocytic-like cells. The extranodular areas were mainly composed of Leu-1+/Leu-4+ lymphocytes with Leu-3a+/OKT4+ phenotype and, to a lesser extent, of OKT6+ OKT10+ lymphoid cells and scattered cells with markers of histiocytic lineage. The abundant vascular component was generally identified by laminin positivity and, in smaller proportion, it was positive for Factor VIII-related antigen. Most of the medium-sized vessels with high endothelium had marked AP, ANAE, and ATPase activities. The process observed resulted from vascularized nodular aggregates of nontransformed B-cells with the phenotype of primary follicle lymphocytes, associated to centrinodular histiocytic-like cells with a distinct enzyme profile.
Cancer 1986 Aug 15
PMID:Immunohistochemical, enzyme histochemical, and immunologic features of giant lymph node hyperplasia of the hyaline-vascular type. 242 88

Factors influencing the activity of the nucleoside analogue arabinosyl-5-azacytosine (ara-AC) were studied in P388 murine lymphoblasts in vitro and in vivo, in variants of these cells with artificially acquired resistance, in the naturally resistant colon 38 carcinoma in vivo, and in a panel of six human tumors maintained in continuous culture. Differences were noted not only between the sensitive and artificially developed resistant variants of P388, but also between the naturally sensitive (P388) and naturally resistant (colon 38) tumors. The artificially developed resistant P388 cell lines showed an inhibited capacity to accumulate nucleotides derived from ara-AC and deoxycytidine, whereas the accumulation of cytidine nucleotides remained unchanged. Studies of the initial velocity of facilitated diffusion of ara-AC showed only minor differences between parental and resistant lines, while the nucleotide formation rates from both ara-AC and deoxycytidine were markedly depressed in the latter cells. It is concluded, therefore, that the failure of resistant P388 cells to accumulate these compounds results not from a transport deficit per se but rather from a failure to convert the nucleosides to nondiffusible (i.e., phosphorylated) species inside the cell. This failure was accompanied by a substantial reduction in the incorporation of a radiolabeled product derived from deoxycytidine into the nucleic acids of the resistant clones. The common factor responsible for the resistance of P388 variants toward ara-AC appears to be a markedly decreased level of deoxycytidine kinase activity. The naturally resistant colon 38 carcinoma, on the other hand, in addition to a decrease in the activity of its deoxycytidine kinase, showed a lower level of activity of all its purine and pyrimidine kinases, along with a notably elevated nucleoside triphosphatase activity (with ATP as substrate) when compared to P388. These differences were reflected in lower endogenous nucleoside triphosphate pool sizes in colon 38, and in a lower level of ara-AC-5'-triphosphate accumulation in colon 38 than in P388 after comparable drug exposure. In the six human tumor lines, a positive correlation was established between sensitivity to ara-AC (as determined by its median inhibitory concentration) and cellular content of deoxycytidine kinase. It is concluded that this latter enzyme is a generally important determinant of sensitivity to arabinosyl-5-azacytosine.
Cancer Res 1986 Sep
PMID:Arabinosyl-5-azacytosine: mechanisms of native and acquired resistance. 242 54


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