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)

The purpose of the experiments was to determine if changes in the post-transcriptional processing of RNA in the hepatoma also affect the low molecular weight nuclear RNA which is transcribed from families of related genes and associated with non-histone chromosomal proteins. Separation of non-histone chromosomal proteins on Sephadex G-200 into three fractions separated the low molecular weight RNA associated with these proteins into metabolically stable RNA firmly bound to the first eluted fractions of high molecular weight non-histone chromosomal proteins, and into a metabolically active RNA which is eluted with the third protein fraction and can be separated from the low molecular weight non-histone chromosomal proteins by chromatography on DEAE-Sephadex A 25 (fraction III RNA). In liver as well as in hepatoma, this fraction III RNA represents about 50% of the RNA associated with the non-histone chromosomal proteins. Fraction III RNA from both tissues has an approximate molecular weight of 13,000, is rich in guanylic acid, is lacking dihydropyrimidines and is copied from the repetitive sequences of DNA. The content of uridylic acid is much higher in fraction III RNA isolated from hepatoma than in the same RNA isolated from liver, and competitive hybridization has shown that hepatoma fraction III RNA contains not only new base sequences which are not present in liver fraction III RNA, but also lacks some sequences which are present in the liver RNA. The technique of RNA/DNA hybridization in the presence of competing RNA has shown that, in hepatoma, the cytoplasmic RNA competes with more than 60% of the fraction III RNA for the hybridization sites on repetitive DNA. No competition was found when liver cytoplasmic RNA was used. The low ratio of competing hepatoma cytoplasmic RNA or of liver or hepatoma nuclear RNA which is required to displace fraction III RNA from its hybridization with DNA indicates that this RNA is synthesized and in hepatoma is also released into the cytoplasm as a part of larger RNA molecules. The detection of the nucleotide sequences found in liver associated with non-histone chromosomal proteins in the cytoplasm of hepatoma cells is evidence for extensive disruption of the post-transcriptional control in hepatoma.
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PMID:RNA associated with non-histone chromosomal proteins in rat liver and in ascites hepatoma. 17 56

A new form of high molecular weight DNA polymerase [EC 2.7.7.7] (polymerase N) was isolated from the nuclei of rat ascites hepatoma cells. Polymerase C, which was isolated previously from whole cell extract, was also isolated from the nuclei (Tsuruo, T. and Ukita, T. (1974) Biochim. Biophys. Acta 353, 146-159). Polymerase N was not found in the cytoplasmic fraction of the cell, while polymerase C existed in both the nucleus and cytoplasm. The molecular weight of polymerase N (8.7 S) was larger than that of polymerase C (7.4 S). On freezing and thawing, polymerase N was converted to polymerase C. In the nucleus the amount of polymerase N was larger than that of polymerase C. These data suggest that polymerase N, which was specifically present in the nucleus, was a complex form of polymerase C. In in vitro assay, polymerase N showed properties similar to those of polymerase C. Oligoribonucleotide was an effective initiator for the polymerization reaction by polymerase N. The DNA synthesis on single stranded fd phage DNA was greatly stimulated by the concomitant synthesis of RNA.
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PMID:A new form of high molecular weight DNA polymerase in the nuclei of rat ascites hepatoma cells. 17 84

DNA-dependent RNA polymerases (EC 2.7.7.6) were extracted and partially purified form the nuclei of rat ascites hepatoma cells (AH-130) induced by 4-dimethylaminoazobenzene. The patterns of RNA synthesis and the properties of these enzymes were compared with enzymes from the nuclei of rat liver. The specific activity of RNA polymerase in the homogenate from the nuclei of AH-130 cells was the same as normal rat liver nuclei. RNA polymerase was solubilized from the homogenate at high ionic strength and separated into two forms by DEAE-Sephadex column chromatography. Enzymatic characterization showed that these enzymes corresponded to RNA polymerase I and II. RNA polymerase I more effectively transcribed native DNA than denatured DNA at low salt concentration, but at high salt concentration RNA polymerase I effectively transcribed denatured DNA. RNA polymerase II more effectively transcribed denatured DNA. In AH-130 cells the activity of RNA polymerase I was 4 to 5 times higher than RNA polymerase II, and in rat liver the activity of RNA polymerase I was 1.5 to 2 times higher than RNA polymerase II. The activity of RNA polymerase I in AH-130 cells may have increased by induction.
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PMID:A comparative study of DNA-dependent RNA polymerases from rat ascites hepatoma cell nuclei and from rat liver nuclei. 18 Jul 54

The structural parameters necessary for the antineoplastic potency of a new class of anticancer agents, arylsulfonylhydrazones of 2-formylpyridine N-oxide, were examined in mice bearing Sarcoma 180 ascites cells. The findings indicated that (a) replacement of the pyridine ring with benzene, quinoline, or isoquinoline resulted in loss of activity (b) movement of the formylhydrazone side chain from the 2 to the 3 or 4 positions of the pyridine N-oxide produced inactive agents (c) the pyridine N-oxide function was essential for anticancer activity, except for 4-substituted derivatives which were active without the N-oxide group, (d) replacement of the SO2 group by CO resulted in complete loss of activity, and (e) a carbon atom could be inserted between the SO2 and aryl ring with retention of anticancer potency. One of the most active members of this series, 1-oxidopyridine-2-carboxaldehyde p-toluenesulfonylhdrazone, exhibited antineoplastic activity against a broad spectrum of transplanted tumors including Sarcoma 180, Hepatoma 129, Ehrlich carcinoma, leukemia L1210, and a subline of Sarcoma 180 resistant to alpha-(N)-heterocyclic carboxaldehyde thiosemicarbazones. This agent caused inhibition of thymidine-3H and uridine-3H incorporation into DNA and RNA, respectively, of Sarcoma 180 ascites cells; protein biosynthesis was relatively insensitive to the action of this compound.
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PMID:Antineoplastic and biochemical properties of arylsulfonylhydrazones of 2-formylpyridine N-oxide. 18 76

The cytophotometrical analysis of the relationships between the content of DNA--fuchsin and the duration of acid hydrolysis of the intranuclear DNA (the Feulgen reaction) in the Zaidela hepatoma cells allows to see the degree of the DNA--protein binding. The UV irradiation of different wave-lengths (254, 325 and 365 nm, resp.) irrespective of the degree of absorption by nucleic acids, causes changes in chromatin condensation, thus suggesting the labilization of DNA--protein bounds.
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PMID:[The effect of ultraviolet radiation of different wave lengths on the concentration of DNA--fuchsin in the cells of Zajdel's ascitic hepatoma]. 18 82

Deoxyribonucleic acid polymerase-beta (EC 2.7.7.7) FROM THE Novikoff hepatoma has been purified over 200 000-fold (based on the increase in specific activity), by ammonium sulfate fractionation and chromatography on DEAE-Sephadex, phosphocellulose, hydroxylapatite, and DNA-cellulose. The enzyme is remarkably stable through all stages of purification until DNA-cellulose chromatography when it must be kept in buffers containing 0.5 M NaCl and 1 mg/ml bovine serum albumin for stability. The enzyme appears to be homogeneous as evidenced by a single stainable band when subjected to electrophoresis in polyacrylamide gels of different porosity. The stainable band corresponds to the DNA polymerase as determined by slicing sister gels and assaying for enzyme activity. The specific activity of the homogeneous preparation is about 60 000 units/mg. The enzyme lacks detectable exonuclease or endonuclease activity. It has a molecular weight of 32 000 as determined by sodium dodecylsulfate-polyacrylamide gel electrophoresis. In sucrose gradients, the molecular weight is estimated at 31 000. The isoelectric point of the hydroxylapatite fraction enzyme is 8.5. The Novikoff beta-polymerase requires all four deoxyribonucleoside triphosphates, primer-template, and a divalent cation for maximal activity. The apparent Km for total deoxyribonucleoside triphosphate is 7-8 muM and for DNA 125 mug/ml. Activated DNA, rendered 7% acid soluble by DNase I, is the preferred primer-template, although a number of synthetic polynucleotides can by efficiently utilized, particularly in the presence of Mm2+ optimum is 7 mM; the Mn2+ optimum is 1 mM. The pH optimum is 8.4 in Tris-HCl or 9.2 in glycine buffer. The beta-polymerase is sstimulated about twofold by NaCl or KCl at an optimum of 50-100 MM, and the enzyme maintains considerable activity at high ionic strengths. The DNA polymerase is inhibited by ethanol, acetone, and a variety of known polymerase inhibitors. Glycols stimulate the enzyme as does spermine or spermidine. Unlike most beta-polymerases, the Novikoff enzyme is moderately sensitive to N-ethylmaleimide.
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PMID:Novikoff hepatoma deoxyribonucleic acid polymerase. Purification and properties of a homogeneous beta polymerase. 18 3

Pyrazofurin (PYF), a C-riboside, inhibited the replication of cultured Novikoff rat hepatoma cells, HeLa cells, and mouse L-cells at concentrations as low as 0.1 to 10 muM, but Novikoff cells were more sensitive than the cells of the other two cell lines. Inhibition of cell replication was completely prevented by the presence of 0.1 to 1 mM uridine in the medium, and partly by the presence of other pyrimidine, but not purine nucleosides. A 2- to 4-hr treatment of the cells with 10 muM PYF resulted in a 2-fold increase in the rate of incorporation of uridine into the acid-soluble pool and nucleic acids, while the rate of incorporation of adenosine into RNA was reduced about 85%. The incorporation of adenosine and deoxyuridine into DNA were reduced about 85 and 50%, respectively. The results are consistent with the view that PYF inhibits the de novo synthesis of pyrimidine nucleosides. The inhibition of cell replication seems to be due mainly to an inhibition of DNA rather than RNA synthesis, resulting from a rapid depletion of the pyrimidine deoxynucleotide pool, since addition of thymidine and deoxycytidine reversed the inhibition of DNA synthesis and cell replication by PYF. PYF must enter the cells to exert its toxicity since the toxicity of PYF was reduced 70 to 80% by the presence of 8 muM Persantin, a potent inhibitor of the facilitated and simple diffusion of various substrates, in the medium. If PYF is incorporated via normal nucleoside salvage pathways, its affinity for the nucleoside transport system(s) and kinases, must be low since, even at a concentration of 1 mM, it had only a slight effect on the initial rates of incorporation of various nucleosides into the nucleotide pool.
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PMID:Inhibition of de novo pyrimidine nucleotide and DNA synthesis and growth of cultured Novikoff rat hepatoma cells and other cell lines by pyrazofurin (NSC 143095). 18 63

Poly(A) polymerase was extracted from isolated nuclei of rat liver and a rapidly growing solid tumor (Morris hepatoma 3924A). The enzyme from each tissue was purified by successive chromatography on DEAE-Sephadex, phosphoecllulose, hydroxyapatite and QAE-Sephadex. Purified enzyme from both liver and tumor was essentially homogeneous as judged by polyacrylamide gel electrophoresis. Under nondenaturing conditions, enzyme activity corresponded to visible protein and, upon denaturation, a single polypeptide was detected. The enzymes had absolute requirements for Mn2+ as the divalent ion, ATP as the substrate and an oligonucleotide or polynucleotide as the primer. Both enzymes were inhibited by sodium pyrophosphate, N-ethylmaleimide, Rose Bengal, cordycepin 5'-triphosphate and several rifamycin derivatives. The reactions were unaffected by potassium phosphate, alpha-amanitin and pancreatic ribonuclease. However, the liver and hepatoma enzymes differed from each other with respect to apparent Km, primer saturation levels and sensitivity to pH changes. The most striking differences between the enzymes were in their calculated molecular weights (liver, 48000; hepatoma, 60000) and amino acid compositions. Finally, the level of the hepatoma enzyme relative to that of the liver enzyme was at least 1.5-fold higher when expressed per mg DNA.
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PMID:Nuclear poly(A) polymerase from rat liver and a hepatoma. Comparison of properties, molecular weights and amino acid compositions. 18 50

Micrococcal nuclease digestion of mouse TLT liver hepatoma chromatin proceeds rapidly to the point where approximately 35% of the DNA is recoverable by centrifugation of the chromatin DNA through 3M CsCl. The satellite DNA sequence content of this recoverable DNA is the same as whole chromatin DNA (10%). The 11s (penultimate digestion product) monomer, as well as intermediate multiples and relatively undigested large chromatin segments are separable on steep hlycerol gradients. The DNA isolated from these fractions also contains the normal 10% satellite DNA content. Progressive polylysine titration of chromatin followed by nuclease digestion gives anomalous recoveries of DNA but, nonetheless, the satellite sequence content titration of chromatin, followed by pronase and then nuclease digestion, again gave recoverable DNA with a satellite sequence content of 10%. These results are discussed in terms of the conclusion that nucleosome (or upsilon-body) structures are distributed in a random fashion over the genome.
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PMID:Satellite DNA sequence content of polylysine-titratable and nuclease-resistant fractions of mouse liver hepatoma chromatin. 18 39

The mechanism of 5-fluorouridine (FUrd) cytotoxicity in Novikoff hepatoma cells appears to vary under different experimental conditions. Continuous exposure to 1 X 10(-7) M FUrd results in a simple thymineless death that can be prevented by the addition of 1 X 10(-4) M thymidine to the culture medium. In contrast, 1 X 10(-4) M thymidine does not prevent the growth inhibition caused by a 1-hr exposure to 1 X 10(-5) M FUrd, despite the fact that it does prevent the inhibition of DNA synthesis. Although it has no effect on the inhibition of DNA synthesis, 1 X 10(-4) M uridine prevents the growth inhibition caused by a 1-hr exposure to 1 X 10(-5) M FUrd. Since 1 X 10(-4) M uridine, but not 1 X 10(-4) M thymidine, prevents the inhibition of ribosomal RNA maturation caused by a 1-hr exposure to 1 X 10(-5) M FUrd, it seems likely that the effects of the analog on RNA metabolism contribute significantly to the cytotoxic activity of the analog in this specific experimental situation.
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PMID:The mechanism of 5-fluorouridine toxicity in Novikoff hepatoma cells. 18 24


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