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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present report is a continuation of our previous studies on the biochemical mechanisms of carcinogenesis; studying the nature of interactions taking place between Ethylnitrosourea and DNA, RNA and protein of various stages of their synthetic activity. As a model system we chose partially hepatectomized mice live 36 hrs after surgery. Synthetic macromolecule activity in the remaining liver segment was determined by means of 3H-thymidine, 3H-uridine and 3H-leucine. We observed complete depression of DNA synthetic activity (immediately after Ethylnitrosourea administration it remained depressed almost through out the whole period of our observations) while protein synthetic activity was highly elevated. Qualitative changes of soluble proteins which were analyzed by isoelectric fractionation on 5% polyacrylamide after previous 3H- and 14C-leucine incorporation, could not be detected. Our biochemical data are correlated with histological studies and with the tumour incidence following the Ethylnitrosourea treatment of partially hepatectomized mice in the course of long-term experiments. The results provide guideline for further analysis, which should be modified according to the information concerning Ethylnitrosourea carcinogenesis induced 36 hours after partial hepatectmoy.
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PMID:Macromolecular synthetic activity in mice regenerating liver after ethylnitrosourea injection. 15 33

A selective deficiency of uridine triphosphate (UTP) was induced in AS-30D rat ascites hepatoma cells by the synergistic action of D-galactosamine and 6-azauridine. The resistance of these hepatoma cells to low concentrations of D-galactosamine (less than 2 mM) was due to their active de novo pyrimidine synthesis which compensated the trapping of uridylate in the form of uridine diphosphate-amino sugars derived from D-galactosamine. The additional blockage of de novo pyrimidine synthesis led to noncompensated uridylate trapping with a UTP content of less than 0.05 mmole/kg of cell wet weight as compared to the control level of 0.66 mmole/kg. The induction of UTP deficiency by incubating the cells with low concentrations of D-galactosamine and 6-azauridine (0.5 mM each) was not accompanied by significant changes in the content of adenine and guanine nucleotides, uridine diphosphate glucose, and uridine diphosphate galactose. The depletion of UTP pools could be reversed within 10 min by the addition of uridine; orotate or uracil were completely ineffective in these hepatoma cells. A UTP content in the range of 0.1 to 0.4 mmole/kg, induced by either 6-azauridine or D-galactosamine, was associated with a reversible depression of cell growth in suspension culture. A UTP content below 0.05 mmole/kg led to irreversible growth inhibition and to necrocytosis in culture, as well as to a loss of transplantability in vivo. Uridine reversal studies indicated that the percentage of cells able to resume growth in culture decreased with an increasing time period of UTP deficiency. The deficiency period required for irreparable or lethal damage in these hepatoma cells ranged from 3 to 20 hr. The principle of noncompensated uridylate trapping can be extended to other inhibitors of nucleotide synthesis combined with various nucleotide-trapping sugar analogs. Noncompensated nucleotide trapping may be useful for an induction of selective nucleotide deficiencies in tumor cells.
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PMID:Uridine triphosphate deficiency, growth inhibition, and death in ascites hepatoma cells induced by a combination of pyrimidine biosynthesis inhibition with uridylate trapping. 18 18

1. The activation of human peripheral blood lymphocytes by phytohaemagglutinin in vitro was accompanied by striking increases in the concentrations of the natural polyamines putrescine, spermidine and spermine. 2. The enhanced accumulation of polyamines could be almost totally abolished by dl-alpha-difluoromethylornithine, a newly discovered irreversible inhibitor of l-ornithine decarboxylase (EC 4.1.1.17), or by methylglyoxal bis(guanylhydrazone) {1,1'-[(methylethanediylidene)dinitrilo]diguanidine}, an inhibitor of S-adenosyl-l-methionine decarboxylase (EC 4.1.1.50). The inhibition of polyamine accumulation was associated with a marked suppression of DNA synthesis, which was partially or totally reversed by low concentrations of exogenous putrescine, spermidine, spermine and cadaverine and by higher concentrations of 1,3-diaminopropane. 3. In contrast with some earlier studies, we found that methylglyoxal bis(guanylhydrazone), at concentrations that were sufficient to prevent polyamine accumulation, also caused a clear inhibition of protein synthesis in the activated lymphocytes. Similar results were obtained with difluoromethylornithine. The decrease in protein synthesis caused by both compounds preceded the impairment of DNA synthesis. The inhibition of protein synthesis by difluoromethylornithine was fully reversed by exogenous putrescine, spermidine and spermine, and that caused by methylglyoxal bis(guanylhydrazone) by spermidine and spermine. In further support of the idea that the inhibition of protein synthesis by these compounds was related to the polyamine depletion, we found that difluoromethylornithine caused a dose-dependent decrease in the incorporation of [(14)C]leucine into lymphocyte proteins which closely correlated with the decreased concentrations of cellular spermidine. 4. Difluoromethylornithine and methylglyoxal bis(guanylhydrazone) also elicited a variable depression in the incorporation of [(3)H]uridine and [(14)C]adenine into total RNA. The apparent turnover of lymphocyte RNA remained essentially unchanged in spite of severe polyamine depletion brought about by difluoromethylornithine. 5. The present results, as well as confirming the anti-proliferative action of the inhibitors of polyamine biosynthesis, suggest that polyamine depletion may interfere with reactions at different levels of gene expression.
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PMID:Suppression of the formation of polyamines and macromolecules by DL-alpha-difluoromethylornithine and methylglyoxal bis(guanylhydrazone) in phytohaemagglutinin-activated human lymphocytes. 43 70

Marrow cells of a patient with CDA, type III, were (1) incubated with 3H-thymidine for 0.5 h and studied using a combination of Feulgen microspectrophotometry and light microscope autoradiography and (2) incubated with 3H-thymidine, 3H-uridine or 3H-leucine for 1 h and studied using the technique of electron microscope autoradiography. The data revealed multiple abnormalities in the proliferation of erythroblasts but no abnormality in the distribution of neutrophil promyelocytes and myelocytes in the different stages of interphase. Some mononucleate erythroblasts had DNA contents of 4-20c and the multinucleate erythroblasts had total DNA contents of 2-40c. In about 40% of the multinucleate erythroblasts, only some of the nuclei within the same cell incorporated 3H-thymidine and the electron microscope autoradiographic studies revealed that the nuclei which failed to synthesize DNA virtually always showed abnormalities in the electron-density of the heterochromatin or euchromatin or a Swiss-cheese appearance of the heterochromatin. Furthermore, in some multinucleate cells but not in others, the ultrastructurally abnormal nuclei showed a marked depression of RNA synthesis when compared with the normal-looking nuclei within the same cell. An occasional binucleate, multinucleate and giant mononucleate erythroblast showed ultrastructural changes suggestive of advanced degeneration and such cells, which showed a marked depression of RNA and protein synthesis, appeared to be phagocytosed by macrophages.
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PMID:Some aspects of the biology of multinucleate and giant mononucleate erythroblasts in a patient with CDA, type III. 43 98

The administration of the antioxidant, butylated hydroxytoluene (BHT) to rats decreased the utilization of [2-14C]orotic acid for the synthesis of cytidine nucleotides in the acid-soluble extract and RNA of the liver. The specific activity of the uridine components was slightly decreased. The depression of the specific activity of the cytidine components depended on the dose of the drug. Simultaneously preformed [U-14C]cytidine in experimental rats was to a higher degree transported to the liver and incorporated into RNA cytosine; its deamination was markedly suppressed. Both phenomena depend on the BHT dose. The concentration of both the uridine and the cytidine components of the acid-soluble extract remained unaffected by the administration of BHT. The utilization of [2-14C]orotic acid for the synthesis of DNA cytosine was depressed after the administration of BHT; by contrast, the specific activity of DNA thymine was higher. The incorporation of [1-14C]palmitic acid into microsomal phospholipids was not substantially influenced over the dose range 25--500 mg BHT/kg. The specific activity of neutral lipids in microsomes increased.
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PMID:Alterations in metabolism of cytidine components in rat liver after oral administration of butylated hydroxytoluene (in vivo study). 53 68

The bone marrow cells of a patient with congenital dyserythropoietic anaemia, type II, were incubated with 3H-thymidine, 3H-uridine or 3H-leucine for 1 h and studied using the technique of electron microscope autoradiography. Several of the erythroblasts which either displayed the characteristic subsurface double membranes or showed various non-specific abnormalities of the nuclear membrane were found to be actively engaged in DNA, RNA and protein synthesis. Both members of some pairs of erythroblasts which were joined together by a spindle bridge were found to be engaged in DNA synthesis, indicating that some spindle bridges persist for a period longer than the duration of the G1 phase. A small proportion of mononucleate and binucleate late (non-dividing) erythroblasts showed a marked depression or arrest of protein synthesis and some or all of such cells were presumably destined to be phagocytosed by the bone marrow macrophages.
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PMID:Electron microscope autoradiographic studies of the erythroblasts of a case of congenital dyserythropoietic anaemia, type II. 66 56

Uracil and perhaps other natural pyrimidines may effect the level of arousal of the mammalian brain since: 1) heterocyclic 6-membered rings, which resemble uracil, form part of the structure of many hypnotics; and 2) 6-azauracil (and its riboside) have shown to be hypnotic for several mammalian species, including man. The parenteral administration of uridine, 6-azauridine, cytidine or thymidine depressed the spontaneous activity of adult male C-57 mice. 6-Azauridine was much less potent than the other ribosides tested. Cytosine, barbituric acid, 2-thiobarbituric acid, 2,4-dihydroxypyridine and a variety of pyrimidine catabolites had no effect on activity. Thymine, uracil, 6-azauracil, barbital and phenobarbital increased activity at lower doses and decreased activity at higher ones. 6-Azauracil and uracil were about equally potent as stimulants of activity, but 6-azauracil had about twice the potency of uracil as a depressant of activity. Thymine, which was more active than uracil, had about 10% the potency of barbital, both as a stimulant and as a depressant of activity. For thymine and the two barbiturates the ED50 (for depression of activity) was of the same magnitude as the LD50, while the dose which caused 50% stimulation of activity was about an order of magnitude less than the LD50. These results suggest that the barbiturates might affect arousal by simulating the structure of thymine or uracil at some receptor.
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PMID:Effects of natural pyrimidines and of certain related compounds on the spontaneous activity of the mouse. 71 33

Delta 9-Tetrahydrocannabinol (THC) elicited a dose-dependent (3.2-24 muM) response for form/movement, cellular growth and division in log growth phase and division-synchronized Tetrahymena pyriformis GL. Progressive dose-dependent action of THC on division delays in division-synchronized cell cultures was correlated with a concomitant reduction of division maxima and the percent of cells that completed division I. THC depressed the incorporation of 5-3H-uridine, 2-14C-thymidine and L-3-14C-phenylalanine into RNA, DNA and protein macromolecules respectively of division-synchronized Tetrahymena during division I. The depression of incorporation of 5-3H-uridine into nucleic acid macromolecules was correlated with a reduction of exogenous precursor in the cellular pool. The specific activity of radiolabeled mRNA and nascent polypeptides of polyribosomal fractions from synchronized cells was reduced by THC treatment. THC caused an inhibition of the incorporation of 5-3H-uridine into ribosomal RNA (17S and 25S RNA) and ribosomal precursor RNA (35S RNA) of synchronized cells.
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PMID:Action of delta 9-tetrahydrocannabinol on cell division and macromolecular synthesis in division-synchronized protozoa. 81 44

The principal psychoactive component of marihuana is delta-9-tetrahydrocannabinol. This compound at 10(-5) molar concentration in the medium of human cell cultures appeared to inhibit DNA, RNA, and protein synthesis by 50, 40, and 30% respectively, as measured by incorporation of radioactive precursors into acid-insoluble cell fractions in human diploid fibroblasts, human neuroblastoma cells, and mouse neuroblastoma cells. While delta-9-tetrahydrocannabinol inhibited semiconservative DNA synthesis, it had no effect on DNA repair synthesis in human cells as assayed by the photolysis of 5-bromodeoxyuridine incorporation into DNA during repair after ultraviolet radiation damage. Delta-9-tetrahydrocannabinol also had no effect on rejoining of DNA single-strand breaks induced by gamma-rays. The nonspecificity of the inhibition of macromolecular synthesis by delta-9-THC suggested a possible interference with uptake of radioactive precursors. However, experimentation has shown that this depression of macromolecular synthesis cannot be accounted for by reduced transport of radioactive precursors into the cell because the rate of transport of these precursors into the cell is essentially the same in the presence or absence of delta-9-THC. Pool sizes of macromolecular precursors as measured radioisotopically (3H-thymidine, 3H-uridine, 14C-leucine) appear to be reduced about 50%, and this reduced pool size could fully account for the reduced macromolecular synthesis seen in the presence of delta-9-THC. We do not know what causes this apparent reduction of pool sizes in the presence of delta-9-THC.
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PMID:delta-9-Tetrahydrocannabinol: effect on macromolecular synthesis in human and other mammalian cells. 94 11

As a possible more rapid test of lymphocyte reactivity to phytohaemagglutinin (PHA) than the standard estimation of thymidine uptake after 72 hours (T72), uridine uptake after 24 hours (U24) was studied in a total of 96 individuals. No reliable correlation between the two estimations was found in 29 outpatients showing a wide range of reactivity to PHA nor in 30 healthy control subjects nor in 16 pregnant subjects. Conflicting reports have appeared in the literature as to whether lymphocyte reactivity to PHA is normal, depressed or enhanced in pregnancy. Our group of pregnant subjects showed a significant depression of both U24 (P less than 0-01) and T72 (P less than 0-02) results as compared to normal female controls. Cultures of semipurified lymphocytes prepared by gradient centrifugation on a further 21 normal control subjects showed no better correlation between U24 and T72 results than the above unpurified-leucocyte cultures.
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PMID:Comparison of uridine uptake at 24 hours with thymidine uptake at 72 hours in phytohaemagglutinin-stimulated cultures of pregnant and other subjects. 95 55


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