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)

Reduced rates of lipid peroxidation have been observed in Yoshida hepatoma cells and microsomes when compared with appropriate control tissue (normal rat liver) under the same pro-oxidant conditions. The pro-oxidant conditions used were incubation with NADPH+ADP+iron or ascorbate+iron or exposure to gamma-irradiation. As previously shown with the Novikoff hepatoma, the relative concentrations of alpha-tocopherol and polyunsaturated fatty acids are important in conferring resistance to lipid peroxidation in the Yoshida hepatoma. Furthermore, NADPH-cytochrome c reductase and the NADPH-cytochrome P-450 electron transport chain, which are involved in the initiation and propagation of certain types of lipid peroxidation, are found at very much reduced levels in the Yoshida hepatoma. The relative importance of these aberrations are discussed.
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PMID:Studies on lipid peroxidation in normal and tumour tissues. The Yoshida rat liver tumour. 312 76

We describe a rapid and direct assay of NAD(P)H:(quinone-acceptor) oxidoreductase (EC 1.6.99.2) activity in cultured cells suitable for identifying and purifying inducers of this detoxication enzyme. Hepa 1c1c7 murine hepatoma cells are plated in 96-well microtiter plates, grown for 24 h, and exposed to inducing agents for another 24 h. The cells are then lysed and quinone reductase activity is assayed by the addition of a reaction mixture containing an NADPH-generating system, menadione (2-methyl-1,4-naphthoquinone), and MTT [3-(4,-5-dimethylthiazo-2-yl)-2,5-diphenyltetrazolium bromide]. Quinone reductase catalyzes the reduction of menadione to menadiol by NADPH, and MTT is reduced nonenzymatically by menadiol resulting in the formation of a blue color which can be quantitated on a microtiter plate absorbance reader. The reaction is more than 90% dicoumarol inhibitable and menadione dependent. The results are comparable to those obtained by harvesting cells from larger plates, preparing cytosols, and carrying out spectrophotometric measurements.
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PMID:Direct measurement of NAD(P)H:quinone reductase from cells cultured in microtiter wells: a screening assay for anticarcinogenic enzyme inducers. 338 6

The lack of aryl hydrocarbon (benzo[a]pyrene) hydroxylase (AHH) (EC 1.14.14.1) induction by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in a clone of rat hepatoma (HTC cl-1) cells is not caused by the lack of nuclear Ah receptor or by a deficiency in the activity of NADPH-cytochrome c (P-450) reductase. Treatment of HTC cl-1 cell line with TCDD for 18 h in culture resulted in a reproducible 500-600% increase in reductase activity without concomitant expression in AHH activity. These data suggests that TCDD induces cytochrome c reductase activity and that the lack of inducible AHH activity in rat hepatoma cells could reflect a defect in the structural gene (s) encoding for cytochrome P1-450, or an Ah receptor with a faulty DNA binding domain.
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PMID:Evidence that 2,3,7,8-tetrachlorodibenzo-p-dioxin induces NADPH cytochrome c (P-450) reductase in rat hepatoma cells in culture. 339 76

The hepatocarcinogen acetamide, in single doses of 100 and 400 mg/kg b.wt., was shown to act as an initiator in a dose-dependent fashion in rat liver using the Solt-Farber method. Acetamide and its putative metabolite N-hydroxy-acetamide did not cause liver necrosis in single dose experiments. Acetamide showed no evidence for genotoxicity in tests for mutations in Salmonella typhimurium, for DNA damage in rat hepatoma cells or for DNA repair in isolated rat hepatocytes. In contrast, N-hydroxy-acetamide displayed genotoxic activity in all 3 test systems. Neither acetamide nor N-hydroxy-acetamide induced transformation of primary Syrian hamster embryo cells or gave evidence of inhibition of metabolic cooperation in V79 cells. Radiolabelled acetamide and N-hydroxy-acetamide were not bound covalently to proteins in the presence of various metabolic activation systems (microsomes plus NADPH or xanthine/xanthine oxidase, cytosol or cytosol plus acetyl CoA or proline plus ATP). N-Hydroxy-acetamide was cytotoxic to monolayers of isolated hepatocytes at concentrations above 2.5 mM. This cytotoxicity was increased after diethyl maleate treatment, but N-hydroxy-acetamide did not deplete cellular glutathione. A HPLC system was developed for the separation and quantification of acetamide, N-hydroxy-acetamide and acetic acid. No significant excretion of N-hydroxy-acetamide or acetic acid in the urine could be demonstrated after treatment of rats with 100 or 1,000 mg/kg b.wt. of acetamide. The underlying mechanism for the observed initiating effect of acetamide is obscure.
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PMID:Studies on the mechanism of acetamide hepatocarcinogenicity. 355 Jul 69

The oleate (delta 9-18:1)/cis-vaccenate (delta 11-18:1) ratios in phospholipids increased in the order of normal liver, host liver and hepatoma in rats. The amount of oleate increased in phospholipids and decreased in triacylglycerol in the same order, whereas the distributions of cis-vaccenate among the major lipid classes were relatively unchanged among the three kinds of cells. Biochemical bases for these differences were sought by characterizing the microsomal elongation system and by analyzing the elongation and desaturation products in vitro. Kinetic parameters for the elongations of palmitoyl-CoA and palmitoleoyl-CoA did not account for the observed differences in the oleate/cis-vaccenate ratios in these cells. However, the oleate/cis-vaccenate ratios varied depending on the availability of substrates, NADH, NADPH, and malonyl-CoA, in the elongation and desaturation of palmitoyl-CoA. Based on the results, it is proposed that differences in the concentrations of substrates for the elongation and desaturation systems might account at least in part for the differences in the oleate/cis-vaccenate ratios among the three kinds of cells.
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PMID:Variation of oleate/cis-vaccenate ratios and its regulation by substrates in hepatic tissues. 365 90

A procedure is described for the assay of 3-hydroxy-3-methylglutaryl CoA-reductase (HMG-CoA reductase) in a large number of samples with minimal benchwork and within a 24-hr period. The Michaelis constants for HMG-CoA reductase were determined for microsomal enzyme from the liver of normal and cholesterol-fed rats and Morris hepatoma 5123C. The apparent Km D-HMG-CoA was ca. 3.5 microM and was not affected by assay temperature or cholesterol feeding. The apparent Km NADPH for microsomal HMG-CoA reductase was 10-15 microM and similarly was not affected by assay temperature. The Arrhenius plot parameters (activation energy and transition temperatures) were the same whether determined using the reaction velocity from fixed substrate concentrations or V from subtraction curves. This confirmed that values obtained using fixed saturating substrate concentrations are valid and not affected by a temperature-dependent alteration in the affinity of the enzyme for its substrates.
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PMID:Effect of assay temperature on the kinetics of 3-hydroxy-3-methylglutaryl-coenzyme A reductase in rat liver and Morris hepatoma 5123C. 402 89

The disadvantage of a whole cell system for studying the metabolism of xenobiotics is that some substrates and regulatory molecules do not readily cross the cell membrane. The present study describes a technique to permeabilize H-4-II-E rat hepatoma cells for the study of benzo(a)pyrene metabolism. NADPH is an essential cofactor in the in vitro microsomal metabolism of benzo(a)pyrene and has been shown by indirect measurement to be a rate limiting factor in mixed function oxidase activity in whole liver perfusion systems. The role of NADPH has not been directly demonstrated in an intact cell system. Using this permeabilized whole cell system it is possible to directly demonstrate that NADPH is rate limiting in the mixed function oxidation of benzo(a)pyrene.
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PMID:A permeabilized cell system for studying regulation of aryl hydrocarbon hydroxylase: NADPH as rate limiting factor in benzo(a)pyrene metabolism. 406 6

Functions of pyridine nucleotide cofactors NADPH and NADH in N-demethylation of amidopyrine were studied under conditions of normal and malignant states. Contribution of NADH-specific transfer of electrons to microsomal N-demethylation was gradually augmented in the sequence: microsomes from liver tissue of rats with Zajdela hepatoma--microsomes of ascites hepatocytes. In this sequence both synergic effect of these cofactors and the rate of N-demethylcation, if NADH was used as a cofactor, were increased.
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PMID:[The role of pyridine nucleotide cofactors in the reaction of microsomal N-demethylation under normal conditions and in tumor pathology]. 409 Mar 79

Liver microsomes of the rat contain a group of hydroxylating enzymes which are coupled to a greater or lesser degree to the electron flow system. In our studies, enzymes believed to be directly associated with the electron flow chain of NADPH, ferricyanide reduction, cytochrome c, cytochrome P-450 and substrate hydroxylation have been observed in livers obtained from normal, tumor-bearing and whole body irradiated rats as well as in Morris hepatoma 7777 and dimethyl-amino-biphenyl induced breast tumors.A significant difference appeared to exist in the activity of NADPH oxidase, NADP-ferricyanide reductase and benzopyrene hydroxylase when normal liver was compared with the liver obtained from a breast-tumor-bearing animal. Both cytochrome P-450 and cytochrome b(5) were decreased in the tumor-bearing animal.Tissue distribution of benzopyrene hydroxylase in normal, lactating and tumor-bearing Wistar rats has been studied.With the exception of NADPH oxidase, the activities of NADP-cytochrome c reductase, NADPH-ferricyanide reductase, benzopyrene hydroxylase and P-450 were markedly different in liver from Morris hepatoma 7777-bearing Buffalo rat when this was compared with homologous tissue obtained from normal Buffalo rat.Whole-body irradiated animals showed increased P-450 and NADPH oxidase activity in liver as a function of irradiation and there further appeared to be a correlation with decreased ferricyanide reductase activity.
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PMID:Mixed-function oxidation in tumors. 439 26

Incubation of 14C-labeled cis and trans isomers of chlordane with cofactor-fortified mouse hepatic microsomes resulted in binding of insecticide-derived material to endogenous protein and RNA and to added DNA. The microsomes were prepared from male C57BL/6J mice. Chlordane is known to cause hepatocellular carcinoma in a similar strain. The highest concentrations of radioactive material bound to protein, followed by RNA and DNA. The cis isomer produced greater amounts of bound radioactivity, while binding from trans-chlordane was slight and, in the case of DNA, not detectable. Investigation of the effect of microsomal enzyme induction by chlordane isomers and phenobarbital on the yield of bound, chlordane-derived material gave mixed results. Generally, use of induced microsomes increased binding to protein and DNA and had no effect on binding to RNA. The inducers caused increased mixed-function oxidase activity, cytochrome P-450 content, and epoxide hydratase activity in experimental microsomes. Omission of the NADPH generating system from microsomal preparations had a variable effect on binding. Inhibition of epoxide hydratase reduced cis-chlordane-related binding to DNA to unmeasurable levels.
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PMID:Microsomal activation of chlordane isomers to derivatives that irreversibly interact with cellular macromolecules. 616 95


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