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)

An experimental study using human melanoma (NEL-MI), rat hepatoma (Fu5-5), and human kidney (293-31) cell lines was undertaken in order to evaluate the antitumor activity of 4-hydroxyanisole (4-OHA) in vitro. Prior reports have indicated highly specific antitumor activity of 4-OHA against melanoma cells in vitro. This specific antitumor activity has been proposed to be due to the oxidation of 4-OHA by tyrosinase to cytotoxic oxidation products. Dose-dependent cytotoxicity was observed when cells were cultured for 72 h in the presence of 4-OHA. At 100 microM, 4-OHA produced growth inhibition of 62%, 32%, and 55% in melanoma, hepatoma, and kidney cell lines, respectively. No effect was seen at 10 microM 4-OHA. 1,000 microM 4-OHA produced 100% kill. Tyrosinase activity was detected only in melanoma cells. The effect of 100 microM 4-OHA on the incorporation of 3H DNA precursors in melanoma, hepatoma, and kidney cells was also studied. Thymidine incorporation was inhibited in all three cell lines at the lowest cell density tested, with the greatest inhibition seen on melanoma cells. As cell density increased, the effect of 4-OHA on thymidine incorporation decreased. With respect to RNA synthesis, 4-OHA significantly reduced the incorporation of uridine in all three cell lines, with the greatest effect in melanoma cells. Cell density also affected the inhibition of uridine incorporation, but to a lesser extent than that observed on thymidine incorporation. The effect of 4-OHA on leucine incorporation was modest and uninfluenced by cell density. Thus, cytotoxicity of 4-OHA may involve two different mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Specificity of growth inhibition of melanoma by 4-hydroxyanisole. 249 44

The hypothesis that the glucocorticoid hormone receptor interacts with RNA has been tested in cultured rat hepatoma cells. The receptor was covalently labeled with radioactive dexamethasone mesylate, and putative RNA-receptor complexes were stabilized by either cell-free crosslinking using formaldehyde or irradiation of intact cells. After chemical cross-linking in vitro, the receptor displayed the buoyant density of a ribonucleoprotein in CsCl gradients. After photochemical crosslinking in cells labeled with radioactive uridine, the receptor analysed by polyacrylamide gel electrophoresis was carrying labeled ribonucleotides.
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PMID:Association of the glucocorticoid hormone receptor with ribonucleic acid. 257 82

Antibody molecules directed against RNA polymerase I, the enzyme responsible for rRNA synthesis, were introduced into rat hepatoma cells by red cell-mediated microinjection. Access of the antibodies to the nucleolus, the site of rRNA synthesis, was facilitated by microinjecting mitotic cells. Using indirect immunofluorescence, anti-RNA polymerase I immunoglobulins, but not control immunoglobulins, were found localized in the nucleoli of microinjected cells. To assess whether intracellular antibodies could alter RNA synthesis, cultures were labeled with [3H] uridine at various times after microinjection. Reduction in RNA synthesis, relative to cells microinjected with non-immune immunoglobulins, was observed within three hours. These results demonstrate that antibodies introduced into the cytoplasm of mitotic cells via red cell-mediated microinjection have free access to nuclear components and that they remain functional within the nuclei of living cells.
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PMID:Reduction in RNA synthesis following red cell-mediated microinjection of antibodies to RNA polymerase I. 258 11

Human apolipoprotein (apo)-B mRNA undergoes a novel tissue specific editing reaction which replaces a genomically templated cytidine with uridine. This substitution converts codon 2153 from glutamine (CAA) in apo-B100 mRNA to a stop codon (UAA) in apo-B48 mRNA. This novel RNA editing process is responsible for the generation of hepatic apo-B100 and intestinal apo-B48. We have established the following concerning this process: (1) by transfection of a series of deletion mutants into the rat hepatoma cell line McArdle 7777, which makes both apo-B100 and apo-B48, we have defined a minimum sequence of 26 nucleotides that is required for apo-B mRNA editing. The sequence containing the modified nucleotide forms a 26 nucleotide highly conserved stem loop with the modified nucleotide occurring in an 8-base loop. (2) Conversion in vitro of apo-B mRNA has been established, using cell free S100 cytoplasmic extract and synthetic RNA templates. Activity was abolished by protease treatment. (3) Transgenic mice were created which expressed a human apo-B construct spanning the stop codon. Apo-B mRNA was found in all tissues examined and this was shown to undergo editing. (4) In the rat liver, which produces apo B-100 and apo-B48, modulation of the relative proportion of these proteins by thyroxine was demonstrated to be mediated at the level of the RNA editing mechanism. It is concluded that apo-B mRNA is edited by a generally expressed protein and editing is highly regulated.
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PMID:RNA editing: a novel mechanism for regulating lipid transport from the intestine. 260 64

The metabolism of chemical carcinogens was investigated in liver preparations from 28 captive woodchucks (Marmota monax). Of these, 23 were naturally infected with the woodchuck hepatitis virus (WHV), and eight also had primary hepatocellular carcinoma (PHC). Twenty-nine parameters were investigated in liver subcellular fractions, including cross-reactivity with HBsAg, and biochemical parameters, such as gamma-glutamyl transpeptidase, cytochrome P-450 and microsomal monooxygenases (aryl hydrocarbon hydroxylase, ethoxycoumarin and ethoxyresorufin deethylases, aminopyrine and dimethylnitrosamine demethylases, and testosterone 7 alpha-, 16 alpha- and 6 beta-hydroxylases), uridine 5'-diphosphoglucuronosyl transferase, GSH and related enzymes (peroxidase, reductase and S-transferase), as well as other cytosolic enzyme activities (glucose 6-phosphate and 6-phosphogluconate dehydrogenases, NADPH- and NADH-dependent diaphorases, and DT diaphorase). In addition, liver preparations were used in order to quantify the metabolic activation into bacterial mutagens of five procarcinogens (aflatoxin B1, the pyrolysis products Trp-P-2 and MeIQ, 2-aminofluorene and dimethylnitrosamine) and the decrease of potency of three direct-acting mutagens (sodium dichromate, ICR 191 and 4-nitroquinoline 1-oxide). WHV infection produced a significant stimulation of carcinogen metabolism, as shown by the simultaneous change in detoxification parameters (GSH depletion) and activation indices (enhancement of microsomal monooxygenases and of procarcinogen activation into mutagenic metabolites). There were no significant differences between WHV-positive samples from animals without PHC and the noncancerous tissue of PHC-bearing animals, whereas a decrease of both activation and detoxification indices was recorded in the tumorous tissue. There was a considerable interindividual variability among WHV carriers, which was tentatively ascribed to genetic factors. Pregnancy was the only known factor influencing the results in WHV carriers. However, even by excluding pregnant animals, the effects on carcinogen metabolism produced by WHV infection were still statistically significant. These results, together with previous data obtained in humans, revealed that metabolic factors may play a role in the synergism between viral hepatitis and chemical hepatocarcinogens in the etiopathogenesis of PHC.
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PMID:Enhanced metabolic activation of chemical hepatocarcinogens in woodchucks infected with hepatitis B virus. 272 Sep 3

Apolipoprotein (apo) B mRNA undergoes a novel tissue-specific editing reaction, which replaces a genomically templated cytidine with uridine. This substitution converts codon 2153 from glutamine (CAA) in apo B100 mRNA to a stop codon (UAA) in apoB48 mRNA (Powell, L. M., Wallis, S. C., Pease, R. J., Edwards, Y. H., Knott, T. J., and Scott, J. (1987) Cell 50, 831-840). To examine sequences in the human apoB mRNA required for the editing reaction, a series of deletion mutants around the cytidine conversion site was prepared and transfected into a rat hepatoma cell line (McArdle 7777). This cell makes both apoB100 and apoB48. Editing was detected by a primer extension assay on cDNA that had been amplified by the polymerase chain reaction. RNAs of between 2385 and 26 nucleotides spanning the conversion site underwent similar levels of conversion. Editing was confirmed by cloning and sequencing of cDNA corresponding to the transfected RNAs. Conversion did not occur in transfected human hepatoblastoma (HepG2) or epithelial carcinoma (HeLa) cell lines, which do not make apoB48. These results verify that apoB48 is generated by a genuine tissue-specific RNA editing reaction and show that 26 nucleotides of apoB mRNA are sufficient for editing.
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PMID:Sequence requirements for apolipoprotein B RNA editing in transfected rat hepatoma cells. 276 26

An assay that employs nucleoside 5'-O-(2-thiotriphosphates) was used to detect initiation of mouse mammary tumor virus (MMTV) RNA chains in preparations of isolated nuclei from cultured rat hepatoma cells containing stably integrated proviruses. RNA chains initiated with adenosine 5'-O-(2-thiotriphosphate), guanosine 5'-O-(2-thiotriphosphate), or uridine 5'-O-(2-thiotriphosphate) were separated from the remaining RNA by mercury-Sepharose column chromatography and analyzed for correctly initiated RNA chains with a T1 nuclease protection assay. Combined use of the thionucleotide transcription reaction with the T1 nuclease assay allowed precise localization of the transcription start sites. The majority of MMTV RNA chains were initiated with guanosine 5'-O-(2-thiotriphosphate) at a template site 133 nucleotides upstream from a PvuII site that coincides with the right end of the long terminal repeat. However, some RNA chains were also initiated with adenosine 5'-O-(2-thiotriphosphate) and uridine 5'-O-(2-thiotriphosphate) at template sites within three nucleotides of the primary guanosine start site. When Mn2+ was substituted for Mg2+ in the transcription reaction, MMTV RNA chains were initiated with approximately the same efficiency, but the start site was shifted to a position approximately 40 nucleotides downstream from the physiological start site; in the presence of Mn2+, MMTV RNA chains were initiated only with guanosine 5'-O-(2-thiotriphosphate). When the nuclei were exposed to both Mn2+ and Mg2+, transcription initiated at the manganese-dependent site. Mn2+ also caused the transcription start site for 45 S pre-rRNA to shift about 10 nucleotides upstream from the physiologically correct start site.
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PMID:A role for divalent cations in specifying the start site for transcription from chromatin templates in vitro. 283 93

The transfer of Morris hepatoma cells induced by the hormone within 10-60 min in to a hormone-free medium is associated with the augmentation of tyrosine aminotransferase synthesis. The kinetics of this process does not differ from that of the hormone-induced enzyme. The return of tyrosine aminotransferase synthesis to the basal level occurs 15-20 hours after the hormone withdrawal from the medium, although the concentration of the intranuclear hormone sharply decreases already after 3 hours. It was demonstrated that the presence in the hepatoma cell nuclei of 20-25% of the initially bound hormone for at least 20 hours after the cell transfer to the hormone-free medium is not sufficient for maintaining a high level of tyrosine aminotransferase gene expression. Using two-dimensional electrophoresis of 3H-labeled hepatoma cell proteins, it was demonstrated that the observed high activity of tyrosine aminotransferase is due to the de novo synthesis of enzyme molecules rather than to the existence of preformed long-living tyrosine aminotransferase molecules inside the cell. Study of [14C]uridine incorporation into non-ribosomal nuclear RNA of hepatoma cells showed a long-term presence of the label in the RNA throughout the chase experiment. It was assumed that the high activity of the enzyme for 10-15 hours after the hormone release from the hepatoma cell nuclei is due to the accumulation in the nuclei of long-living pre-mRNA molecules synthesized after the hormone addition to the cells and during the first hours after the cell transfer to the hormone-free medium.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Hormonal induction of tyrosine aminotransferase and RNA synthesis in the cells of Morris hepatoma strain 7777]. 286 Sep 28

Treatment of H-4 rat hepatoma cells with 8-bromo-cyclic AMP (8-Br-cAMP) resulted in a transient induction of the gluconeogenic enzyme tyrosine aminotransferase. Synthesis of tyrosine aminotransferase and the level of its corresponding mRNA peaked 2 h after the addition of the cyclic nucleotide and declined thereafter. Tyrosine aminotransferase synthesis and mRNA failed to respond to the readdition of fresh 8-Br-cAMP, a process which we defined as desensitization. Removal of 8-Br-cAMP resulted in a decrease in tyrosine aminotransferase synthesis and mRNA, a process defined as de-induction. The relative transcription rate of the tyrosine aminotransferase gene and the turnover of its mRNA were determined by labeling intact cells with [3H]uridine. 8-Br-cAMP led to an increase in the rate of tyrosine aminotransferase transcription which was sustained for at least 4 h. The transcription rate declined upon de-induction. In addition, 8-Br-cAMP increased the turnover rate of tyrosine aminotransferase mRNA, but only after a 1.5-3 h time lag. This increased degradation rate persisted for at least 1.5 h after the removal of 8-Br-cAMP. These two contrasting and temporally distinct processes could account for the observed changes in tyrosine aminotransferase mRNA levels in response to 8-Br-cAMP treatment and removal.
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PMID:Increased turnover of the messenger RNA encoding tyrosine aminotransferase can account for the desensitization and de-induction of tyrosine aminotransferase by 8-bromo-cyclic AMP treatment and removal. 290 63

Rat liver coated vesicle preparations were frequently found to contain small ovoid bodies, which resembled coated vesicles in morphology. We have purified these bodies to homogeneity using sucrose density gradients and preparative agarose gel electrophoresis. When negatively stained and viewed by electron microscopy, the purified structures display a very distinct and complex morphology, resembling the multiple arches which form cathedral vaults. They measure 35 X 65 nm and are therefore considerably larger than ribosomes. When subjected to SDS PAGE, these structures, which we refer to as vaults, appear to contain several minor and five major species: Mr 210,000, 192,000, 104,000, 54,000, and 37,000. One of these (Mr 104,000) greatly predominates, accounting for greater than 70% of the total Coomassie Brilliant Blue-staining protein. Another major species of Mr 37,000 has been identified as a species of small RNA of unusual base composition (adenosine 12.0%, guanosine 29.7%, uridine 30.9%, and 27.4% cytidine), which migrates as a single species in urea PAGE between the 5S and 5.8S ribosomal standards, containing approximately 140 bases. Although the RNA constitutes only 4.6% of the entire structure, the large size of the particle requires that each one contains approximately 9 molecules of this RNA. Antibodies prepared against the entire particle are largely specific for the major (Mr 104,000) polypeptide species. Although they do not directly react with the RNA constituent on Western blots, these antibodies immunoprecipitate a 32P-labeled RNA of identical size from metabolically-labeled rat hepatoma cells. Vaults are observed in partially purified fractions from human fibroblasts, murine 3T3 cells, glial cells, and rabbit alveolar macrophages. It therefore appears that these novel ribonucleoprotein structures are broadly distributed among different cell types. The function of vaults is at present unknown.
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PMID:Isolation and characterization of a novel ribonucleoprotein particle: large structures contain a single species of small RNA. 294 44


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