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

Rat liver and hepatoma nuclei were incubated in vitro with [3H]nicotinamide adenine dinucleotide to allow synthesis of a polymer of adenosine diphosphoribose subunits joined in an 1',2' ribose-ribose linkage. The addition of 1 mM spermine altered the adenosine 5'-diphosphate (ADP) ribosylation patterns of nuclear proteins in hepatoma, host liver, and regenerating liver. Spermine-treated nuclei showed a greater incorporation of ADP-ribose into H1 histones and nonhistone nuclear proteins with isoelectric points between pH 3.0 and 6.0 when separated on polyacrylamide gels. Conversely, a large reduction in ADP ribosylation was seen in core histones (H2A, H2B, and H3) from the same nuclei. The proportion of ADP-ribose incorporated into histones was reduced in the nuclei from proliferating cells relative to their respective control livers. These results imply that polyamines, which are higher in concentration in rapidly dividing cells, may elicit a regulatory function by causing the preferential ADP ribosylation of H1 histones, as well as the more acidic of the nuclear proteins.
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PMID:Spermine-induced variations in the adenosine 5'-diphosphate ribosylation patterns of nuclear proteins from rat liver and hepatoma. 42 Dec 22

Exposure of hepatoma 1c1c7 cells to 2,3-dimethoxy-1,4-naphthoquinone (DMNQ) resulted in a sustained elevation of cytosolic Ca2+, DNA single strand breaks and cell killing. DNA single strand break formation was prevented when cells were preloaded with either of the intracellular Ca2+ chelators, Quin 2 or BAPTA, to buffer the increase in cytosolic Ca2+ concentration induced by the quinone. DMNQ caused marked NAD+ depletion which was prevented when cells were preincubated with 3-aminobenzamide, an inhibitor of nuclear poly-(ADP-ribose)-synthetase activity, or with either of the two Ca2+ chelators. However, 3-aminobenzamide did not protect the hepatoma cells from loss of viability. Our results indicate that quinone-induced DNA damage, NAD+ depletion and cell killing are mediated by a sustained elevation of cytosolic Ca2+.
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PMID:Intracellular Ca2+ chelators prevent DNA damage and protect hepatoma 1C1C7 cells from quinone-induced cell killing. 235 10

The O6-methylguanine-DNA-methyltransferase (transferase) activity in a rat hepatoma cell line (H4 cells) is enhanced as a response to DNA damaging agents. To study whether poly (ADP-ribosylation) is involved in this induction, the cells were treated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) that induces the transferase activity and stimulates poly (ADP-ribose) synthesis. Addition of poly (ADP-ribose) polymerase inhibitors enhanced the transferase increase induced by MNNG. The influence of the inhibitors on the transferase induction was dose and time-dependent. The results suggest that poly (ADP-ribose) is involved in the induction of this protein.
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PMID:Potentiation of N-methyl-N'-nitro-N-nitrosoguanidine-induced O6-methylguanine-DNA-methyltransferase activity in a rat hepatoma cell line by poly (ADP-ribose) synthesis inhibitors. 250 71

Starvation of a mouse hepatoma cell line, Hepa, for any essential amino acid results in the mono-ADP-ribosylation of an 80-kDa protein, P80. The ADP-ribose acceptor and its putative precursor were identified in two-dimensional gel patterns and isolated by electroelution. Amino-terminal sequence analysis showed they were the 78-kDa glucose-regulated protein, GRP78. Starvation of Hepa cells for tryptophan or glucose stimulated the relative rate of synthesis, and the ADP-ribosylation of GRP78. Inhibition of N-linked glycosylation by treatment with tunicamycin, 2-deoxy-D-glucose or glucosamine stimulated the synthesis of non-ADP-ribosylated GRP78 up to sixfold with relatively little effect on its ADP-ribosylation. Both forms were identified in mouse liver, lung, heart, kidney, spleen and brain.
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PMID:ADP-ribosylation of the 78-kDa glucose-regulated protein during nutritional stress. 251 84

The inhibitory effects of nicotinamide analogs on the activity of poly(ADP-ribose)) synthetase were compared to effects on precursor incorporation into macromolecules in three lines of hepatoma cells (Morris hepatomas 5123C, 7777 and HTC). N'-methylnicotinamide was a less effective inhibitor of poly (ADP-ribose) synthetase than was 1-methylnicotinamide while both these compounds had smaller inhibitory effects on the enzyme than were seen with nicotinamide or 3-aminobenzamide. On the other hand, the incorporation of [3H]thymidine into DNA and of [3H]uridine into RNA were inhibited by N'-methylnicotinamide in the concentration range 2-20 mM but not by 1-methylnicotinamide. Under the conditions examined there were no significant effects on the incorporation of [14C]lysine and [3H]leucine in hepatoma cells. The data indicated that the inhibitory effect of N'-methylnicotinamide on nucleic acid synthesis may be unrelated to action on poly (ADP-ribose) synthetase.
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PMID:Disparity in the effects of two N-methyl nicotinamides on poly(ADP-ribose) synthetase and macromolecular synthesis in hepatomas. 299 58

Starvation of the mouse hepatoma cell line Hepa for an essential amino acid (Trp, His, Leu, Ile or Phe) stimulated the incorporation of [3H]adenosine as ADP-ribose monomer into an 80,000-Mr protein, P80. Two-dimensional electrophoresis of Hepa proteins showed that P80 was the only protein labeled under starvation conditions. Time course experiments showed that the ADP-ribosylation of P80 was a consequence rather than the cause of reduced translational activity. Cycloheximide treatment and incubation at reduced temperatures also reduced the rate of protein synthesis and stimulated the ADP-ribosylation of P80. Starvation-dependent ADP-ribosylation of P80 was shown to occur in three other cell lines (Chang, Neuro-2a, and chick comb fibroblasts).
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PMID:Translational control of ADP-ribosylation in eucaryotic cells. 379 12

Treatment of hepatoma AH 7974 cells with dimethyl sulfate led to a marked accumulation in vivo of mono)ADP-ribosyl)-histone H1A, H1B, H1 and H2B, respectively. In these conjugates, most of the modifying groups were linked to the acceptor proteins by an 'unusual' bond not described so far for ADP-ribosyl histone conjugates. It resisted treatment with 3M hydroxylamine, 0.1M picrylsulfonate and mild alkali, which excluded a linkage through carboxyl or guanidino residues. The stability of these conjugates formed endogenously differed also from 'non-enzymic' histone H1 conjugates formed by incubation of free ADP-ribose with the histone. Histone-linked mono(ADP-ribosyl) residues synthesized in hepatoma cells in response to alkylation were located exclusively in the domains that interact with DNA, i.e. in the non-globular C-terminal tail of histone H1 and in the N-terminus of histone H2B. Besides poly(ADP-ribosyl)ation, the modification of histones by single ADP-ribose groups may represent an independent process to modulate DNA/histone interaction.
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PMID:Alkylation-induced mono(ADP-ribosyl)-histones H1 and H2B. Hydroxylamine-resistant linkage in hepatoma cells. 402 97

Three types of ADP-ribosyl proteins (poly(ADP-ribose) conjugates, NH2OH sensitive and NH2OH resistant mono(ADPR) conjugates) could be found in all eukaryotic cells so far studied. They changed independently under various conditions and showed an uneven subcellular distribution suggesting independent functions. Treatment of Ehrlich ascites tumor (EAT) cells with monofunctional or cross-linking alkylating agents led to rapid fragmentation of DNA and depletion of NAD while poly(ADPR) polymerase activity showed a retarded increase. Endogenous amounts of poly(ADPR) groups increased 4- to 30-fold, depending on dose, with the same initial kinetics as the loss of NAD and the appearance of DNA strand breaks. Turnover of poly(ADPR) was determined from the decay rate of the polymer after the addition of benzamide to alkylated cells. At peak elevation of poly(ADPR), an apparent half-life of about 1 min was obtained (control cells: t/2 much greater than 3 hr). There was also an accumulation of nuclear mono(ADPR) conjugates with a half-life of about 10 min. In contrast to in vitro experiments, histone H1 in vivo proved to be only a minor acceptor of ADPR groups in rat liver and in hepatoma cells. It carried less than 0.2% of total monomeric, and less than 2% of total polymeric ADPR residues. Alkylation of cells increased mono(ADP-ribosyl)ation of histone H1 to a much higher degree than poly(ADP-ribosyl)ation. Addition of benzamide to alkylated cells inhibited poly(ADPR) formation and NAD depletion, but interfered with neither DNA fragmentation nor with DNA resealing. Nevertheless, benzamide was a very effective co-cytostatic.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Functional aspects of mono- and poly(ADP-ribosyl)ation: subcellular distribution and ADP-ribosyl turnover under conditions of repair and 'starvation'. 665 28

ADP-ribosylation in vivo of histone H1 was studied in hepatoma cells (Yoshida AH 7974) after treatment with the alkylating agent dimethyl sulfate for 30 min and compared with that of other polypeptides. In unstimulated cells, histone H1 was only a minor acceptor (less than 4%) of total monomeric and polymeric ADP-ribosyl residues. Induction of DNA repair by dimethyl sulfate treatment increased total mono(ADP-ribosyl) protein conjugates 1.6-fold whereas histone H1-linked mono(ADP-ribosyl) groups were elevated greater than 30-fold, thus accounting for nearly one-fourth of the net increase in monomeric ADP-ribosyl residues. In contrast, histone H1-associated poly(ADP-ribosyl) residues comprised only 2% of the total increase in poly(ADP-ribose). The extent to which the histone H1 population became ADP-ribosylated was low even in dimethyl sulfate-treated cells. Less than 2% of the histone H1 molecules were mono(ADP-ribosyl)ated and only 0.003% carried poly(ADP-ribosyl) chains when an average chain length of 10 is assumed. The principal polypeptide acceptors of alkylation-induced ADP-ribosylation were concentrated in two peaks, one migrating close to the position of core histones H3/H2B and accepting most of the induced mono(ADP-ribosyl) and poly(ADP-ribosyl) residues. The other (Mr = 110,000-160,000) resembled auto-modified poly(ADP-ribose) polymerase. Our data demonstrate marked differences of alkylation-induced (ADP-ribosyl)n protein patterns to analyses performed in vitro.
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PMID:DNA repair-associated ADP-ribosylation in vivo. Modification of histone H1 differs from that of the principal acceptor proteins. 669 2

Nuclear mono- and poly(ADP-ribosyl) protein conjugates formed in living hepatoma AH 7974 cells in response to treatment with the alkylating agent dimethyl sulfate have been studied. They were isolated from the perchloric acid precipitate of freshly prepared nuclei in a relatively pure form and with an overall yield of more than 80%, utilizing aminophenylboronic acid-agarose chromatography. Exposure of the cells to 400 microM dimethyl sulfate led to a transient rise of ADP-ribosylated proteins. After 20 min, the level of endogenous poly(ADP-ribosyl) residues increased by a factor of 21, amounting to a final value of 772 +/- 57 pmol/mg of DNA while the mono(ADP-ribosyl) residues were raised to even higher concentrations (1864 pmol/mg of DNA), corresponding to a 12-fold stimulation as compared to untreated cells. As a result of dimethyl sulfate treatment, the amount of acceptor protein being modified by (ADP-ribose)n was elevated 15-fold, reaching a final proportion of 2.3 +/- 0.4% of total nuclear protein. The increase in (ADP-ribosyl)n-modified proteins was suppressed by benzamide, a potent inhibitor of poly(ADP-ribose) synthetase. More than half of the nuclear mono- and poly(ADP-ribosyl) residues were linked to histone H2B. The modifying residues could be removed from the major acceptor by treatment with 0.1 M NaOH, but not with neutral hydroxylamine. Minor amounts of other histones, especially of histone H4, were possibly also ADP-ribosylated under the stimulating effect of dimethyl sulfate. In addition, several nonhistone proteins with apparent molecular masses of 100-116 and 170 kDa were found to carry substantial amounts of mono- and poly(ADP-ribose).
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PMID:ADP-ribosylation of nuclear proteins in vivo. Identification of histone H2B as a major acceptor for mono- and poly(ADP-ribose) in dimethyl sulfate-treated hepatoma AH 7974 cells. 672 73


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