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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Incorporation of uracil and uridine into ribonucleic acid (RNA) was compared among the ascitic and solid forms of Ehrlich mouse tumor, Morris hepatoma, Rhodamine sarcoma, gastric cancer and ulcer from human patients, and several normal rat tissues. Of these cells tested, the cells of Ehrlich ascites and solid tumors, human gastric cancer and ulcer, and certain tissues of a normal rat showed a considerably high activity. Furthermore, Ehrlich ascites tumor cells indicating a high incorporation activity was also high in activities of both phosphorylase and kinase for uridine, while Rhodamine sarcoma as a representative having a low incorporation activity was considerably low in these two enzymic activities. RNA synthesis from uridine phosphates by Rhodamine sarcoma was maintained to a fairly high extent contrary to its low activities of the phosphorylase and the kinase. Consequently, the low utilization of uracil and uridine by certain tumors was suggested to be due to the extremely low activities of both enzymes.
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PMID:Incorporation characteristics of uracil, uridine, and orotic acid into ribonucleic acid of neoplastic cells. 19 18

Interaction between the de novo and salvage pathways of pyrimidine metabolism was studied in a line of rat hepatoma cells by co-labelling with [14C]-uridine and [3H]orotate. A difference in the ratio of 14C/3H between CTP and UTP in acid-soluble nucleotide pool was reflected in the corresponding ratios in CMP and UMP in RNA, with uridine labelling cytidine nucleotides relatively more effectively than orotate. These results are not compatible with the concept of a single UTP pool, and a new model for pyrimidine anabolic pathways, based on compartmentation of de novo from salvage pathways, is proposed.
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PMID:Evidence for compartmentation of uridine nucleotide pools in rat hepatoma cells. 57 61

The interrelationship between nuclear RNP particles and chromatin in Zajdela hepatoma cells double labelled with 3H-thymidine and 14C-uridine was investigated by three independent methods (Nucleoprotein-Celite chromatography, sucrose density and CsCl band centrifugations). All nuclear RNP particles were found to be associated with the chromatin. Some of chromatin-associated RNA molecules are polyadenylated, thus indicating the post-transcriptional character of this association. DNA and RNA molecules in these complexes are bound through protein rather than being connected directly. The site of contact between RNP particle and chromatin is relatively resistant to the action of DNase I and pancreatic RNase. The experiments with exogeneous labelled RNP particles added to isolated nuclei do not reveal the formation of artificial RNP-chromatin complexes. The results obtained are discussed in the light of current views on the nucleus-to-cytoplasm transport of RNA molecules.
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PMID:[Post-transcriptional association of RNP particles with chromatin in Zajdela ascities hepatoma cells]. 69 10

The effects of increasing extracellular concentrations of Ca2+ and Mg2+ on the uptake of 14C-thymidine, 3H-uridine and 14C-leucine by Novikoff hepatoma and normal liver cells have been studied. Increasing concentrations of Ca2+ stimulate all the three incorporations while Mg2+ exhibits an inhibitory effect. Liver cells presented a higher cation permeation induced by the extracellular concentration than hepatoma cells which also seems to explain the quantitative differences observed in the studied syntheses. The importance of the extracellular cation-cell membrane interaction in these effects is discussed.
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PMID:Effects of extracellular Ca2+ and Mg2+ on nucleic acids and proteins syntheses by tumor and normal liver cells. 70 Sep 6

When cell cultures were incubated with certain oxygenated derivatives of cholesterol which specifically depress 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity (i.e. 25-hydroxycholesterol, 7-ketocholesterol, or 20 alpha-hydroxycholesterol), a number of consequences followed the decline in enzyme activity. DNA synthesis, expressed in terms of (methyl-3H)thymidine incorporation/mg of cellular protein, declined progressively after the addition of an inhibitor to L-cell cultures and had essentially ceased by 80 h. A decline in the rate of cell growth, as determined by the measurement of cellular protein, became apparent about 24h after the addition of the inhibitor. These effects of the inhibitory sterols were reversed when mevalonate or cholesterol was added to the medium within 48 h after the addition of the inhibitor. Specific rates of uridine incorporation into RNA and of leucine into protein were not significantly altered during 80 h of incubation with the inhibitor. Sterol synthesis was suppressed; and the concentration of desmosterol in L-cells declined to about one-half of the control level within 36 h. Since phospholipid concentrations were not altered significantly by the treatment, the molar ratio of sterol to phospholipids declined to levels lower than any previously reported for mammalian cells. Changes in the molar ratio of sterol to phospholipids in plasma membranes isolated from L-cells that had been incubated with 25-hydroxycholesterol or cholesterol were in agreement with those found in cells under similar conditions. The inhibitory sterols caused a similar but slower decline in the concentrations of unesterified and total cholesterol in fetal mouse liver cell cultures and rat hepatoma cell cultures.
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PMID:Consequences of blocked sterol synthesis in cultured cells. DNA synthesis and membrane composition. 83 34

Novikoff rat hepatoma cells were propagated in suspension cultures containing 0.5 to 10 muC of 3H-methyl-thymidine, 3H-5-uridine, 3H-G-adenosine or 3H-8-adenine. The presence of the 3H-labeled precursors caused an inhibition of cell replication which was due to a delay or arrest of the cells in G2 and M. The degree of inhibition was proportional to the amount of radioactivity incorporated into nucleic acids. Almost immediate and complete inhibition resulted from incubation with 10 muC 3H-thymidine/ml. The presence of 0.5 muC 3H-thmidine/ml caused a significant increase in the relative proportion of cells in G2+M, even though the population doubling time of the culture appeared to be unaltered.
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PMID:G2+M arrest of cultured mammalian cells after incorporation of tritium-labeled nucleosides. 83 7

Cytochalasin B competitively inhibits the transport of 2-deoxy-D-glucose and thymidine in a number of different cell lines (Novikoff rat hepatoma cells, mouse L, S180 and Ki-MSV-transformed BALB/3T3 cells, and human HeLa cells). The apparent Km values for the transport of these substrates as well as the apparent Ki values for the inhibition by cytochalasin B are very similar for the various cell lines, and the effect is readily and completely reversed by removal of the chemical. Thymidine transport by Chinese hamster ovary cells however, is little affected by cytochalasin B, whereas the transport of 2-deoxy-D-glucose, uridine and guanine by these cells is competitively inhibited to about the same extent as in other cell lines. In addition and concomitant with the inhibition of cytokinesis and an alteration in cell shape, cytochalasin B also impairs and delays the formation of functional transport sites for thymidine, guanine and choline in synchronized populations of Novikoff cells without affecting the apparent affinities of the transport systems for their substrates. This effect is unrelated to the direct inhibition of the transport processes, since the drug does not directly inhibit choline transport and has no effect on the formation of 2-deoxy-D-glucose transport sites in spite of the fact that it strongly inhibits the transport of this substrate. The inhibition of functional transport sites may be due to the induction of a structural alteration in the membrane by cytochalasin B which impairs the insertion of new proteins of certain but not all transport systems into the membrane.
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PMID:Membrane effects of cytochalasin B. Competitive inhibition of facilitated diffusion processes in rat hepatoma cells and other cell lines and effect on formation of functional transport sites. 116 81

The effects of nutritional variables on the processing of exogenous precursors into RNA was examined. General nutritional deprivation, or asparagine depletion, led to significant changes in the absolute pool sizes, especially of ATP, UTP and CTP. Fluctuations were found depending on the elapsed time after the nutritional perturbations occurred, and the cell density of the cultures. Depletion of the medium by 28 h of growth, or 1 h of guinea pig asparaginase action, led to considerable inhibition of the conversion of exogenous uridine to CTP by the cells. A series of experiments indicated that in 6C3HED lymphoma cells the uridine nucleotide pool which provided the immediate precursors to RNA (denoted UTP-NA) behaves as a small compartment in rapid equilibrium with exogenously supplied nucleosides. The resemblance to the compartmentation model described by Plagemann (Plagemann, P.G.W. (1972) J. Cell Biol. 52, 131-146 and (1971) J. Cell. Physiol. 77, 241-258) for rat hepatoma cells was close. The UTP-NA pool of the 6C3HED cells constitutes no more than 5% of the cellular UTP pool and is relatively slow in equilibrating with the general cell pool. Correction of the rates of incorporation of isotope into RNA by using some function of the whole cell UTP specific activity to normalize the pool effects, was shown to be invalid.
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PMID:Nutritional effects on precursor uptake and compartmentalization of intracellular pools in relation to RNA synthesis. 117 50

Glucocorticoid hormones act in the nucleus of the cell to alter expression of specific genes and change cell metabolism. In liver, these hormones have been reported to increase mitochondrial respiratory activity, which is regulated by both nuclear and mitochondrial gene products. We examined the effects of the synthetic glucocorticoid, dexamethasone, on the expression of mitochondrially encoded genes in a rat hepatoma cell line, H-4-II-E cells. Dexamethasone treatment of these cells increased mitochondrial RNA (mtRNA) levels 3- to 4-fold without changing the amount of mitochondrial DNA mtRNA levels could increase by enhanced mitochondrial gene transcription, by decreased degradation, or by some combination of the two. To determine if messenger RNA (mRNA) stabilization contributed to the increase in mtRNA levels, we compared the decay rates of cytochrome b mRNA from dexamethasone-treated and control cells after inhibition of RNA synthesis; cytochrome b mRNA half-life was 80 min in both treatment conditions. The levels of incompletely processed RNA precursors for at least two mtRNAs increased 3-fold more and 24 h earlier than the mature mRNAs. These results suggested that dexamethasone treatment resulted in increased mtRNA transcription. In addition, we examined the incorporation of [3H]uridine into mtRNA. Dexamethasone treatment expanded the uridine triphosphate pools 1.6-fold in H-4-II-E cells and decreased uridine triphosphate specific activity 2.3-fold; correcting for this change in precursor pool specific activity demonstrated increased mtRNA synthesis in dexamethasone-treated cells. Changes in expression of nuclear-encoded proteins that regulate mitochondrial genome transcription are a possible mechanism by which dexamethasone can increase mtRNA levels in these cells.
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PMID:Dexamethasone treatment increases mitochondrial RNA synthesis in a rat hepatoma cell line. 137 Jul 90

Nitrobenzylthioinosine (NBTI) was systematically modified by attachment of substituents at the 2-, 5'-, 3'- and 2'-positions in order to assess the importance of these positions in the binding of NBTI to high-affinity membrane binding sites (Kd < or = 1 nM) and the inhibition of NBTI-sensitive, equilibrative nucleoside transport by mammalian cells. We determined the effect of the derivatives on the equilibrium binding of 1 nM [3H]NBTI to human erythrocytes and mouse P388 leukemia cells and on the inhibition of zero-trans influx of formycin B in P388 cells and equilibrium exchange of uridine in human erythrocytes. Placement of substituent groups at the 5'-position of NBTI had relatively little effect on its binding to high-affinity binding sites or its inhibition of nucleoside transport, regardless of the size of the substituent group (up to about 1000 kDa). All substituents at the 2-position considerably reduced the affinity of NBTI to membrane binding sites and its potency as an inhibitor of nucleoside transport, but some substituent groups reduced the affinity of binding more than the inhibition of nucleoside transport. The effect of the 2-substituents was not directly related to their size. Attachment of a succinate at the 3'- or 5'-position also reduced to a greater extent the binding of NBTI than its inhibition of nucleoside transport, which was relatively little affected. Attachment of succinates at both the 3' and 5'-positions almost completely abolished both binding to high-affinity sites and inhibition of nucleoside transport. Both functions of NBTI were abolished completely by the simultaneous blockage of the 2'- and 3'-positions. None of the NBTI derivatives significantly inhibited NBTI-resistant equilibrative formycin B transport in P388 and Novikoff rat hepatoma cells at concentrations of < or = 1 microM.
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PMID:Effects of chemical modification of nitrobenzylthioinosine on its binding to high-affinity membrane binding sites and inhibition of nucleoside transport. 141 82


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