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)

During eight successive isologous passages of hepatoma induced in male C3HA mice by N-nitrosodiethylamine, no common features of tumor progression were observed, although both the mitotic pattern and ploidy differed from generation to generation. These additional cytologic criteria allowed the biochemical examination of material least changed due to tumor progression. Tumor nDNA's were characterized by greater actinomycin D (AD)- and acridine orange (AO)-binding abilities than were normal nDNA's; this could have resulted from a higher proportion of double-stranded regions in tumor DNA. Isolated tumor deoxyribonucleoprotein had both lower template activity in an RNA polymerase system and fewer AD- and AO-binding sites, when compared with the activity and sites from normal mouse liver. RNA-DNA hybridization data with the above-mentioned findings showed that in hepatoma, part of the nuclear genome was repressed. Also, RNA "new classes" appeared and a certain proportion of nuclear genes controlling mitochondrial protein biosynthesis were derepressed in tumor mitochondria. The hybridization of mitochondrial RNA (mtRNA) and DNA revealed new classes of pulse-labeled RNA's in in vitro-incubated liver mitochondria that were absent from intact cell organelles; the hybridization properties of in vivo- and in vitro-formed hepatoma mtRNA's were similar. Competition and hybridization experiments demonstrated that in tumor mitochondria in vivo, some new classes of RNA existed. Hepatoma mitochondrial mRNA had a higher metabolic stability than did normal mRNA.
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PMID:Nucleic acids from subcellular fractions of N-nitrosodiethylamine-induced hepatoma in mice. 18 62

Cytokines have been implicated in the modulation of fat metabolism after sepsis. Carnitine palmitoyltransferase (CPT), the regulatory enzyme of hepatic mitochondrial long-chain fatty-acid oxidation, is involved in the control of hepatic fat oxidation in sepsis. Using either H4IIe rat hepatoma cells or rat hepatocytes in primary culture, we tested the hypothesis that interleukin-1-alpha (IL-1 alpha) would modulate CPT transcription (CPT mRNA), CPT translation (35S-methionine CPT protein incorporation), and hepatic mitochondrial oxidation of 1-Carbon 14-labeled (14C) palmitate to ketone bodies (acid soluble products). We showed that IL-1 alpha significantly increased CPT mRNA, 35S-methionine incorporation CPT protein, and hepatic mitochondrial oxidation of 1-14C-palmitate to acid soluble products. We further hypothesized that the Ca2+ second messenger system may play a role in the IL-1 alpha induction of hepatic CPT gene transcription. We showed that either calcium ionophore (A23187) or phorbol myristate acetate increased CPT gene transcription and that either calcium chelation, protein kinase C inhibition (acridine orange), or chronic exposure to phorbol myristate acetate significantly inhibited IL-1 alpha induction of CPT mRNA. We conclude that the IL-1 alpha increases in hepatic mitochondrial fatty-acid oxidation may be, in part, secondary to increased CPT gene transcription and translation and that the Ca2+ second messenger system may play an important role in IL-1 alpha induction of CPT gene transcription.
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PMID:The Ca2+ second messenger system and interleukin-1-alpha modulation of hepatic gene transcription and mitochondrial fat oxidation. 185 38

Two closely related hepatoma cell lines were examined for their genotoxic response to benacridines and their metabolites by the appearance of alkaline labile DNA sites: H5, a dedifferentiated line expressing cytochrome P-448-dependent mono-oxygenase(s); and HF1-4, a differentiated line expressing cytochrome P-450-dependent monooxygenase(s). The parent heterocycles had no effect on both cell lines. In contrast to the 3,4-dihydrodiol of benz[c]acridine the 3,4-dihydrodiol of benz[a]acridine induced no DNA strand breaks in both cell lines. All diol epoxides, however, induced DNA-damage in both cell lines, the syn derivatives in the same order of magnitude as the dihydrodiol of benz[c]acridine. The antidiol epoxides (epoxide group on the opposite side to the benzylic hydroxyl group) were the most potent to induce DNA-single strand breaks. The diol epoxide of benz[c]acridine was three times more efficient in HF1-4 than in H5, whereas for the diol epoxide of benz[a]acridine, the reverse was true. The results indicate that benz[c]acridine-3,4-diol is oxidized to metabolites which can induce DNA-damage. This is consistent with the hypothesis that the benz[a]acridine and derivatives are not easily metabolized to active mutagens but more likely are converted to inactive metabolites, possibly via N-oxidation. This is illustrated with 3,4-diol-1-2 anti-diol epoxide of benz[a]acridine which is inactivated in cell line HF1-4 due to the reactivity of the epoxide ring in the bay region. Since all diol epoxides show similar activity in both hepatoma cell lines, they are of great interest because of their ability to detect DNA-damaging agents and to analyse their metabolic activation and mechanism of action.
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PMID:Differentiated genotoxic response of carcinogenic and non-carcinogenic benzacridines and metabolites in rat hepatoma cells. 397 58

This study reports on the ultrastructural location and biophysical properties of cell-associated glycosaminoglycans of AH-130 cells, an azo dye-induced ascites hepatoma. Earlier studies have shown that a low-sulfated heparan sulfate, which comprises 93% of their total glycosaminoglycan (GAG) content, is associated with these cells. High-iron diamine, an ultrastructural stain for sulfated glycoconjugates, stained the hepatoma cell surfaces heavily. With the exception of occasional light staining in a few cytoplasmic granules, intracellular organelles did not stain with this method. The lack of an extensive pool of intracellular GAG was confirmed by quantitative fluorescence microscopy of cells vitally stained with acridine orange. The nature of the binding of the cell-surface heparan sulfate was explored by competitive binding studies with exogenous heparin. When cells were incubated with exogenous heparin, release of heparan sulfate into the medium was not detected, although heparin was bound. We conclude that low-sulfated heparan sulfate is an integral component of the AH-130 hepatoma cell surface and is bound at a site different than heparin.
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PMID:Heparan sulfate of AH-130 ascites hepatoma cells: a cell-surface glycosaminoglycan not displaced by heparin. 616 66

The signal transduction pathway involved in the activation of pyruvate dehydrogenase (PDH) by insulin is still unknown. In this study, we have examined the possible involvement of protein kinase C (PKC) in the process. In addressing this question, we examined (1) the insulin-like effects of the PKC activator 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA) on the PDH complex, (2) the effects of various PKC inhibitors on the PDH activation by insulin, and (3) the response of PKC-depleted cells to insulin. We used as an experimental model Zajdela hepatoma cultured (ZHC) cells, which have been demonstrated to be responsive to physiological doses of insulin. Half-maximal and maximal stimulations of the PDH complex by insulin were observed at 0.05 and 5 nmol/L, respectively. Stimulation of PDH activity by insulin (5 nmol/L) occurred within 5 minutes of incubation and was maximal (+70%) at 7.5 minutes. In the presence of PMA (162 nmol/L), enzyme activity increased within 30 seconds, was maximal (+90%) at 5 minutes, and was no longer detectable after 10 minutes. Total PDH activity was unchanged by insulin or PMA treatment. The effects of PMA and insulin on basal PDH activity were not additive. Moreover, various inhibitors of PKC--staurosporine, sphingosine, acridine orange--completely blocked the stimulation of PDH activity induced by insulin or PMA. A 17-hour treatment of ZHC cells with 500 nmol/L PMA efficiently downregulated PKC, as attested by the marked decrease in the enzyme activity and the loss of phorbol 12,13-dibutyrate binding to intact cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evidence for a role of protein kinase C in the activation of the pyruvate dehydrogenase complex by insulin in Zajdela hepatoma cells. 805 43

An efficient chemical procedure for the immobilization of carboxylate containing conjugate groups onto controlled pore glass (CPG) is described. The derivatized supports were used in the automated synthesis of an oligodeoxynucleotide (20-mer ODN) containing a 3' phosphodiester linked hexanol, aminohexyl, acridine, or cholesterol group. The stability of the oligomer in a hepatoma cell culture was found to be prolonged two to three fold by the presence of any of the 3' tails. By contrast, an aminohexyl group appended to the 5' terminus of the ODN only marginally improved its nuclease resistance. These data support the notion that antisense ODNs are primarily degraded by 3' exonucleases. Introduction of simple 3' tails which incorporate a normal phosphodiester linkage can increase ODN stability by interfering with these enzymes.
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PMID:Facile preparation of nuclease resistant 3' modified oligodeoxynucleotides. 838 90

Fumonisin B1 is associated with various animal and human carcinomas and toxicoses, including leukoencephalomalacia, hepatocarcinoma, pulmonary edema and esophageal carcinoma. We have examined the cellular effects of fumonisin B1 in vitro using cellular model systems relevant to potential human target tissues. Although fumonisin B1 has been described as a mitogen in Swiss 3T3 cells based on stimulation of [3H]thymidine incorporation, in the current work it was found that fumonisin B1 inhibited incorporation of [3H]thymidine by cultured neonatal human keratinocytes and HepG2 human hepatocarcinoma cells at 10(-7) and 10(-4) M respectively. Fumonisin B1 also inhibited clonal expansion of normal human keratinocytes and HET-1A human esophageal epithelial cells at 10(-5) M and growth in mass culture of normal human fibroblasts at 10(-7) M. The clonogenicity of normal human keratinocytes decreased to 45.5% of controls after exposure to 10(-4) M fumonisin B1 for 2 days. However, no differences in the cell cycle distribution of cultured keratinocytes was noted after exposure to 10(-5) M fumonisin B1 for 40 h. The viability of normal human keratinocytes and HET-1A cells decreased as a result of fumonisin B1 treatment, as determined by a fluorescein diacetate/propidium iodide flow cytometric cell viability assay. Fumonisin B1-treated keratinocytes released nucleosomal DNA fragments into the medium 2-3 days after exposure to 10(-4) M fumonisin B1 and increased DNA strand breaks were detected in attached keratinocytes exposed to 0-10(-4) M fumonisin B1 using a terminal deoxynucleotidyl transferase-based immunochemical assay system. Furthermore, fumonisin B1-treated keratinocytes and HET-1A cells developed morphological features consistent with apoptosis, as determined by phase contrast microscopy, fluorescent microscopy of acridine orange stained cells and electron microscopy. These results are consistent with the occurrence of fumonisin B1-mediated apoptosis in vitro.
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PMID:Apoptotic and anti-proliferative effects of fumonisin B1 in human keratinocytes, fibroblasts, esophageal epithelial cells and hepatoma cells. 862 45

Salvia miltiorrhiza (SM) is a traditional Chinese herbal medicine, commonly used to treat liver diseases in China for centuries. Several earlier studies have indicated that SM exhibits anti-tumor properties, but its mechanism remains to be elucidated. In this study, we evaluated the molecular mechanism of SM in a human hepatoma cell line, HepG(2). Our results show that SM exerted clear cytotoxic effects, and strongly inhibited the proliferation of HepG(2) cells. It was also observed that SM treatment caused apoptotic cell death as evaluated by: (a), morphological changes by using acridine orange/ethidium bromide staining; (b), DNA fragmentation by TdT-mediated dUTP nick end labeling (TUNEL); and (c), sub-G(1) cell analysis. Furthermore, depletion of intracellular glutathione (GSH) and reduction of mitochondrial membrane potential were found to be involved in the initiation of apoptosis by SM.
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PMID:Salvia miltiorrhiza inhibits cell growth and induces apoptosis in human hepatoma HepG(2) cells. 1077 35

Nitrated polycyclic aromatic hydrocarbons (NPAHs) and N-heterocyclic aromatic hydrocarbons (azaarenes) are as ubiquitous in the environment as their parent PAH compounds, although occurring at lower concentrations. The toxicological importance of NPAHs and azaarenes is based on their mutagenic and carcinogenic potential. Azaarenes possess a higher solubility and mobility in the environment than PAHs. However, very little is known about the toxicity and cytochrome P450 (CYP)1A induction potencies of NPAHs and azaarenes in fish. Here we report on the cytotoxicities and relative CYP1A induction potencies of 12 NPAHs, 12 azaarenes, and 11 PAHs, determined as neutral red uptake and ethoxyresorufin-O-deethylase (EROD) activity, respectively, in fish hepatoma PLHC-1 cells. Additionally, CYP1A enzyme protein was determined by ELISA for two NPAHs, azaarenes, PAHs, and binary mixtures. Compared with the structurally analogous PAHs, 2-nitronaphthalene, 3-nitrofluoranthene, 2-aza- and 7-azafluoranthene, 1,6-dinitropyrene, benzo[a]acridine and benzo[h]quinoline revealed higher induction potencies, whereas the other compounds showed similar or less activity. The induction potency was highly dependent on the compounds structural properties, reflected by significant correlations between the half-maximal EROD induction (-log EC50) and the molecular descriptors lipophilicity (log Kow) and maximal molecular length (Lmax). Binary mixtures of 6-nitrochrysene + benzo[a]anthracene, 6-nitrochrysene + benzo[a]acridine, and benzo[a]acridine + benzo[a]anthracene showed an additive interaction. The CYP1A induction potencies of NPAHs and azaarenes, demonstrated here for the first time in fish hepatoma cells, suggest that their contribution to the overall CYP1A induction potencies in PAH-contaminated environmental samples have to be taken into account.
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PMID:Cytochrome P450 induction by nitrated polycyclic aromatic hydrocarbons, azaarenes, and binary mixtures in fish hepatoma cell line PLHC-1. 1135 3

Intensive apoptotic death of thymocytes is a possible mechanism of thymus involution during tumor growth. We studied the role of hypercholesterolemia and lactate acidosis in the induction of increased sensitivity of thymocytes to apoptosis during growth of transplanted hepatoma 22a in mice. Spontaneous apoptosis in thymocytes during tumor growth in mice was studied in vitro by acridine orange/ethidium bromide staining and diphenylamine test. Plasma levels of lactate, total cholesterol, alpha-cholesterol, and triglycerides were measured. A positive correlation was found between intensification of apoptosis (diphenylamine test) and increased concentration of total plasma cholesterol on days 21 and 28 after inoculation of tumor cells. Plasma lactate content did not increase at this term. We hypothesize that hypercholesterolemia accompanying tumor growth acts as a factor increasing thymocyte sensitivity to apoptosis.
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PMID:Effect of metabolic factors on apoptosis in thymocytes during tumor growth. 1291 Feb 89


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