Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Site-specific binding of nitrobenzylthioinosine (NBMPR) to plasma membranes of some animal cells results in the inhibition of the facilitated diffusion of nucleosides. The present study showed that nucleoside transport in Novikoff UA rat hepatoma cells is insensitive to site-saturating concentrations of NBMPR. Equilibrium binding experiments demonstrated the presence of high-affinity sites for NBMPR in a membrane-enriched fraction from these cells. In the presence of uridine or dipyridamole, specific binding of NBMPR at these sites was inhibited. When Novikoff UA membranes were covalently labelled with [3H]NBMPR by using photoaffinity techniques, specifically bound radioactivity was incorporated exclusively into a polypeptide(s) with an apparent Mr of 72,000-80,000, determined by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. Covalent labelling of this polypeptide was abolished in the presence of excess nitrobenzylthioguanosine (NBTGR) and reduced in the presence of adenosine, uridine or dipyridamole. The apparent Mr of the NBMPR-binding polypeptide in Novikoff UA cells is significantly higher than that reported for corresponding polypeptides in other cell types (Mr 45,000-66,000). When membrane-enriched preparations from S49 mouse lymphoma cells were photolabelled and mixed with labelled NovikoffUA membrane-enriched preparations, gel electrophoresis resolved the NBMPR-binding polypeptides from the two preparations.
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PMID:Photoaffinity labelling of a nitrobenzylthioinosine-binding polypeptide from cultured Novikoff hepatoma cells. 379 87

The association of nucleolar phosphoprotein C23 with preribosomal ribonucleoprotein (RNP) particles was examined in Novikoff hepatoma nucleoli. RNA was labeled with [3H]uridine for various times in cell suspensions, and RNP particles were extracted from isolated nucleoli and fractionated by sucrose gradient ultracentrifugation. The majority of protein C23 cosedimented with fractions containing rapidly labeled RNA (RL fraction). To determine whether there was a direct association of RNA with protein C23, the RL fraction was exposed to ultraviolet (UV) light (254 nm) for short periods of time. After 2 min of exposure there was a 50% decrease in C23 as measured by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analyses, with no significant further decrease at longer times. When UV-treated fractions were subjected to phenol/chloroform extractions, as much as 30% of the labeled RNA was found in the phenol (protein) layer, indicating that RNA became cross-linked to protein. Similarly, there was an increase in protein C23 extracted into the water layer after irradiation. By SDS-PAGE analyses the cross-linked species migrated more slowly than protein C23, appearing as a smear detected either by [3H]uridine radioactivity or by anti-C23 antibody. With anti-C23 antibodies, up to 25% of the labeled RNA was precipitated from the RL fraction. Dot-blot hybridizations, using cloned rDNA fragments as probes, indicated that the RNA in the RL fraction and the immunoprecipitated RNA contained sequences from 18S and 28S ribosomal RNA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Association of protein C23 with rapidly labeled nucleolar RNA. 379 May 20

Uridylate-trapping analogs of D-galactose or D-glucose divert the uridylate moiety of UDPglucose and/or UTP to UDP-sugar analogs that accumulate while the pools of UTP and of related pyrimidine nucleotides are depleted. The uridylate-trapping action of sugar analogs is determined by the enzyme pattern of the target tissue. D-Galactose analogs are preferentially metabolized by hepatoma cells and hepatocytes. TA3-mammary tumor cells are susceptible to the action of D-glucosamine and other D-glucose analogs. A high rate of de novo pyrimidine synthesis and/or an active salvage of extracellular uridine compensate for the uridylate-trapping action of sugar analogs and prevent depletion of UTP pools. Accordingly, synergistic actions are induced by combining sugar analogs, such as D-galactosamine or D-glucosamine, with inhibitors of de novo pyrimidine synthesis, such as lapachol or 6-azauridine. Uridylate-trapping by D-galactosamine, acting on hepatocytes, shifts the balance between uridine consumption and uridine release by the liver and results in a fall of uridine and cytidine concentrations in blood plasma (20). Cultured hepatocytes produce uridine and cytidine. Combination of 5-fluorouridine with sugar analogs results in the formation of fluorinated UDP-sugar analogs in hepatoma cells or in mammary tumor cells. Formation of FUDP-sugar analogs transiently removes intracellular FUTP, but FUDP can be released subsequently in glycosyltransferase reactions (22). Pretreatment of hepatoma cells or of TA3-mammary tumor cells with an uridylate-trapping sugar analog in combination with an inhibitor of de novo pyrimidine synthesis enhances the uptake of 5-fluorouridine, its incorporation into RNA, and its growth inhibitory effect. The chemotherapeutic action of 5-fluorouridine in rats and mice, carrying the AS-30D and the TA3 ascites tumor, respectively, is significantly improved by pretreatment with an amino sugar together with 6-azauridine.
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PMID:Potentiation of antimetabolite action by uridylate trapping. 383 24

Cultured Novikoff rat hepatoma and Walker 256 carcinoma cells have previously been reported to express only nitrobenzylthioinosine (NBTI)-resistant uridine transport and to lack high affinity NBTI-binding sites, whereas the latter are common on all other types of cultured mammalian cells from different species [1-7) X 10(5) sites/cell) which have been investigated with the exception of a transport-deficient cell variant which lacks high-affinity NBTI-binding sites. The present study shows that lack of NBTI sensitivity of transport and of NBTI-binding sites in Novikoff and Walker 256 cells are not related to the species or tissue origin of these cells. Uridine transport in a variant (NRM) of Novikoff hepatoma cells, in HTC rat hepatoma cells, normal rat kidney (NRK) cells, rat erythrocytes and rat hepatocytes was inhibited 15-60% by 10-500 nM NBTI and the cells expressed high-affinity NBTI-binding sites (Kd = 0.1-0.6 nM). The apparent turnover numbers for the NBTI-sensitive nucleoside carriers fell into two classes, with those for transformed cells about 10-times higher than those for the normal rat cells.
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PMID:Nitrobenzylthioinosine-sensitive and -resistant nucleoside transport in normal and transformed rat cells. 400 49

Carbamoyl-phosphate synthetase II (glutamine hydrolyzing, EC 6.3.5.5) (synthetase II), the rate-limiting enzyme of de novo uridine monophosphate biosynthesis, was purified 230-fold to apparent homogeneity from rapidly growing rat hepatoma 3924A. The antiserum (produced in rabbits against purified hepatoma 3924A enzyme) yielded a single precipitin line with crude and partially purified synthetase II of normal liver and three hepatomas. In hepatomas of slow (20), intermediate (7787), and rapid (3924A) growth rates, synthetase II activity was elevated 1.5-, 2.3-, and 7.9-fold, and the amount of antiserum required to inactivate the activity was 1.6-, 2.3-, and 8.2-fold higher than that in normal liver. Thus the increase in synthetase II activity in the tumors was due to an elevation in the amount of the synthetase II enzyme protein.
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PMID:Increased carbamoyl-phosphate synthetase II concentration in rat hepatomas: immunological evidence. 402 25

Glucocorticoid hormone is shown to markedly suppress DNA synthesis in a line of rat hepatoma cells in vitro. In the presence of 300 nM hydrocortisone or 30 nM dexamethasone the incorporation of radioactive thymidine falls to 50% of control levels by 36 hr, and at higher concentrations of hormone inhibition can be noted as early as 12 hr and is nearly complete by 24 hr. This inhibition of radioactive thymidine incorporation reflects a true suppression of DNA synthesis, is accompanied by a corresponding inhibition of cell proliferation, and is readily reversible upon subsequent removal of hormone. In contrast to previously described effects of the glucocorticoid hormones on various cells of lymphoid origin, the inhibition of DNA synthesis in these hepatoma cells is not accompanied by appreciable cell lysis or by degradation of preformed DNA, and even when [(3)H]thymidine incorporation into DNA is inhibited by 90% or more, incorporation of [(14)C]uridine into RNA proceeds with little change. These findings all parallel previous observations on the effects of glucocorticoid hormone on the livers of intact animals and suggest that studies on the mechanism of the inhibition of DNA synthesis in the present more isolated system may lead to a better understanding of the means by which these compounds inhibit liver growth in vivo. Despite the ready suppressibility of DNA synthesis in these hepatoma cells and in two other cell lines of liver origin, none of these cell lines was found to be inducible for tyrosine aminotransferase. The apparent dissociation between two "steroid-sensitive" phenomena is of interest and warrants further investigation.
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PMID:Suppression of DNA synthesis in hepatoma cells exposed to glucocorticoid hormone in vitro. 414 35

Plagemann, Peter G. W. (Western Reserve University, Cleveland, Ohio), and H. Earle Swim. Replication of mengovirus. II. General properties of the viral-induced ribonucleic acid polymerase. J. Bacteriol. 91:2327-2332. 1966.-Mengovirus induces the appearance of a ribonucleic acid (RNA) polymerase activity in Novikoff hepatoma cells which is readily distinguished from the deoxyribonucleic acid (DNA)-dependent RNA polymerase since it is not inhibited by actinomycin D or deoxyribonuclease, but is inhibited by ammonium sulfate, and is stable at -17 C. The incorporation of uridine into RNA by infected cells in the presence of actinomycin D does not reflect the viral polymerase activity as measured in cell-free preparations. The viral-induced RNA polymerase is produced in a biphasic fashion. Puromycin inhibits the production of viral polymerase, and in its presence the enzyme appears to be unstable between 4 and 6 hr. Puromycin also prevents the secondary rise in polymerase which begins at the end of replicative cycle. Under these conditions, however, the polymerase appears to be stable. The overall data indicated that some unspecified process is responsible for the apparent instability of viral-induced RNA polymerase between 4 and 6 hr and that it becomes inoperative toward the end of the replicative cycle.
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PMID:Replication of mengovirus. II. General properties of the viral-induced ribonucleic acid polymerase. 428 86

1. Twenty minutes after injection of [(3)H]orotic acid into rats the rapidly labelled RNA from the liver is mainly associated with the nuclear fraction and little with the ribosomal cytoplasmic fraction. 2. The thermal denaturation of RNA from the fractions was not as reversible as that of the RNA extracted from whole liver. 3. Rapidly labelled RNA is synthesized by cells from a transplantable hepatoma when incubated in the presence of [(3)H]uridine and, after extraction and centrifugation, the label is present in three main fractions: one which sediments to the bottom of a gradient and is associated with DNA, a second which sediments to the heavy side of the 28s RNA, and a third which has a peak of activity between 28s RNA and 18s RNA and is associated with DNA. 4. After labelling and extraction of the RNA from Ehrlich ascites cells the distribution of radioactive components is similar to that of the material from the hepatoma cells. 5. The difference between the tumour cells and liver is due to some extent to the method of homogenizing the tissues and the nature of the components is discussed.
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PMID:Studies in rapidly labelled ribonucleic acid in cell fractions and in tumour tissues. 429 Apr 8

Cells from a clonal strain (MH(1)C(1)) of rat hepatoma were transplanted subcutaneously into two homozygous Gunn rats, which are jaundiced because the enzyme bilirubin uridine diphosphate-glucuronyltransferase is absent from the liver. Because of the enzyme activity present in the transplanted cells, the recipient rats developed the capacity to conjugate bilirubin and reverted in large part to a normal pattern of bilirubin excretion.
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PMID:Transfer of bilirubin uridine diphosphate-glucuronyltransferase to enzyme-deficient rats. 431 99

This study was undertaken to measure the absolute levels of nucleoside pools in Novikoff rat hepatoma cells (subline N1S1-67) during growth in suspension culture in the presence of high concentrations of various nucleosides in the medium, and to obtain further evidence for the compartmentalization of the nucleotides in independent cytoplasmic and nuclear pools. The levels of nucleotide pools were measured by growing the cells in medium supplemented with inorganic phosphate-(32)P. The nucleotide pool levels (mostly in the form of triphosphates) ranged from about 1 nmole of cytidine nucleotides to 8 nmole of adenosine nucleotides per 10(6) cells. The presence of 1 mM uridine, cytidine, guanosine, or adenosine in the medium resulted in marked increases in the intracellular levels of the corresponding nucleoside phosphates of at least 3-4 nmole/1O(6) cells. These increases were partially compensated for by decreases in the levels of other nucleotides. Evidence is presented to indicate that it is the cytoplasmic pool that expands during incubation with high concentrations of nucleosides in the medium, whereas the nuclear pool remains constant and very small in size. Preincubation of cells with 1 mM uridine-(3)H for 5.5 hr, which resulted in a threefold increase in the total intracellular level of uridine nucleotides, had no effect on the subsequent incorporation of uridine-(14)C into cellular nucleic acids in the nucleus, whether present at a 1 microM or 1 mM concentration in the medium. In contrast, the incorporation of uridine-(14)C into cytoplasmic viral-specific RNA by mengovirus-infected Novikoff cells was reduced 60-70% as a result of preincubation of the cells with high concentrations of uridine-(3)H. Further, within 1-2 min upon addition of 2.5 or 6.5 microM(3)H-labeled uridine, cytidine, adenosine, guanosine, or inosine to cultures of Novikoff rat hepatoma cells, the incorporation of label into nucleic acids reached a constant and maximum rate, in spite of the presence of high intracellular concentrations (0.4-3 mM) of the corresponding unlabeled nucleoside triphosphates. Marked differences were also observed in the relative incorporation of the various nucleosides into the different nucleotides of the acid-soluble pool, and of mengovirus RNA and cellular RNA.
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PMID:Nucleotide pools in Novikoff rat hepatoma cells growing in suspension culture. 3. Effects of nucleosides in medium on levels of nucleotides in separate nucleotide pools for nuclear and cytoplasmic RNA synthesis. 433 Dec 95


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