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 activities of microsomal stearoyl-CoA desaturation, NADH-cytochrome b5 reductase, NADH-cytochrome c reductase, and the content of cytochrome b5 were similar in livers of normal and host rats. On the other hand, stearoyl-CoA desaturation activity was absent in Novikoff hepatoma. The activities of NADH-cytochrome b5 and NADH-cytochrome c reductases in the hepatoma microsomes were 4.8% and 2.2%, respectively, of those in normal liver. Furthermore, in hepatoma microsomes, cytochrome b5 was absent. An active stearoyl-CoA desaturation was reconstituted only on addition of both cytochrome b5 and the terminal desaturase enzyme to the hepatoma microsomes. These results indicated that a complete absence of cytochrome b5 and terminal desaturase is responsible for the lack of stearoyl-CoA desaturation in Novikoff hepatoma microsomes.
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PMID:Stearoyl-coenzyme A desaturase activity in Novikoff hepatoma. 3 26

Microsomal cytochromes and some oxidative activities were determined in normal rat liver, tumour-bearing rat liver and Morris hepatoma 3924-A. Except for a moderate lowering of cytochromes and enzymes in host livers, the relation between TPNH-cytochrome c reductase activity and cytochrome P-450 TPNH reduction, both increased by phenobarbital (PB) and decreased by 3-methylcolanthrene (3-MC) treatment, is noteworthy. In tumour cytochromes b5 and P-450 are absent and TPNH-cytochrome c reductase is unmeasurable and not induced by PB or 3-MC treatment. Aminopyrine demethylase activity, instead, is comparable with normal or host liver and it is modified by PB or 3-MC treatment in the same way, despite the microsomal enzymes pathway disorganization. Microsomal enzymatic defect selectivity in tumours may be due to a deranged microsome-linked growth control.
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PMID:Effects of phenobarbital and 3-methylcolanthrene treatment on microsomes of Morris hepatoma 3924-A, tumour-bearing and normal rat liver. 10 3

1. Ethanol metabolism in slices or homogenates of transplantable hepatocellular carcinoma HC-252 (HC-252) was 50 to 60% of the rate found in host liver slices or homogenates when they were expressed per gram of tissue wet weight and 70 to 80% of the liver when the rates were expressed per milligram of tissue protein. At 10 mM ethanol, the activities of alcohol dehydrogenase in tumor and liver supernatants were comparable. 2. Tumor microsomes did not oxidize ethanol in the presence of a NADPH-generating system, indicating the absence of the microsomal ethanol-oxidizing system and catalase-mediated peroxidation of ethanol. The HC-252 microsomes were contaminated with catalase, and acetaldehyde production occurred in the presence of a H2O2-generating system (xanthine oxidase). The virtual absence of ethanol oxidation and drug metabolism (aminopyrine demethylase and aniline hydroxylase) in HC-252 microsomes may be due to the low activities of NADPH-cytochrome c reductase, NADPH oxidase, and NADPH-dependent oxygen uptake. 3. Microsomal oxidation of ethanol was present in Morris hepatoma 5123C, a well-differentiated tumor of intermediate growth rate, while activity was negligible in microsomes from Morris hepatoma 7288CTC, a less differentiated tumor. Microsomal NADPH oxidase was present in the well differentiated tumor 5123C but was lacking in the less differentiated tumor 7288CTC. Several microsomal, mitochondrial, and cytosolic properties of HC-252 are similar to those of Morris hepatoma 7288CTC but differ from those of the more differentiated 5123C tumor and normal liver. 4. The content of mitochondrial protein in HC-252 was only 25% that of liver, and oxygen consumption per gram of tumor was only 28% that of the liver. When corrected for the mitochondrial protein content, oxygen uptake in tumor HC-252 and liver homogenates was comparable. Isolated tumor and liver mitochondria displayed comparable State 4 and 3 rates of oxygen consumption with succinate and glutamate as substrates. The activities of the reconstituted malate-aspartate and alpha-glycerophosphate shuttles were only slightly lower in isolated HC-252 mitochondria compared to liver mitochondria, when shuttles were reconstituted with purified enzymes. 5. Antimycin inhibited alcohol metabolism,and pyruvate stimulated alcohol metabolism, much less in tumor slices than in liver slices, suggesting the presence of an augmented mitochondria-independent, cytosolic mechanism for oxidizing reducing equivalents in the tumor. These factors suggest that oxidation of NADH is the limiting factor in ethanol metabolism. Whereas, in the liver mitochondrial reoxidation is predominant, in HC-252, cytosolic reoxidation of NADH also plays a major role.
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PMID:Ethanol metabolism by a transplantable hepatocellular carcinoma. Role of microsomes and mitochondria. 13 37

1. Mitochondrial and microsomal fractions were prepared from normal rat liver and the Morris 7777 hepatoma and characterized by the use of the marker enzymes, succinate dehydrogenase and rotenone-insensitive NADPH-cytochrome c reductase. 2. The phospholipid content per mg membrane protein of Morris 7777 hepatoma mitochondria was increased by 75% as compared with mitochondria from normal rat liver. Microsomes from this poorly-differentiated tumor were found to have a 45% decrease in the content of phospholipid. These abnormalities were independent of tumor size or age. 3. The percent phospholipid content of the subcellular fractions was determined, and revealed an increase in the percent sphingomyelin in both the microsomal and mitochondrial fractions of the tumor. Decreases in the percent phosphatidylcholine and phosphatidylethanolamine were noted in tumor microsomes as compared with normal liver. Diphosphatidylglycerol was not found in significant quantities in the microsomal fraction of this hepatoma line. 4. The content of the various phospholipid classes per mg protein in the respective mitochondrial and microsomal fractions was determined. Large increases in nearly all the major phospholipid classes were found in tumor mitochondria; tumor microsomes were characterized by an increased content of sphingomyelin but the content of nearly all other phospholipids was significantly decreased. These findings suggest the presence of disturbances in the regulation of phospholipid metabolism in subcellular organelle membranes of the Morris 7777 hepatoma.
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PMID:Abnormal membrane phospholipid content in subcellular fractions from the Morris 7777 hepatoma. 18 53

The specific activity and subcellular distribution of marker enzymes for the main subcellular components were analysed in homogenates of synchronized hepatoma cells (Morris 7288c), obtained by selective detachment at mitosis combined with a metaphase block with Colcemid. Markers for lysosomes, mitochondrial outer membrane, plasma membrane and cytosol are synthesized throughout the cycle at the same rate as the bulk of cellular protein. Larger variations are observed for a Golgi marker; after a decrease around mitosis, the specific activity of galactosyltransferase increases steadily from middle G(1)-phase on, and at the end of G(2)-phase it is nearly twice that observed at the beginning of G(1)-phase. Our results show that synthesis of cytochrome oxidase may occur preferentially in G(2)-phase. Large modifications of the density distribution of lysosomes are observed during the cell cycle; the median equilibrium density of lysosomal markers decreases in G(1)-phase, and some increase in soluble activity occurs at the same time. Reverse changes occur progressively during S- and G(2)-phases. At mitosis, Golgi galactosyltransferase shows a more dispersed distribution, and modifications in the density distribution of endoplasmic-reticulum NADPH-cytochrome c reductase are observed. The latter can be most easily explained by a detachment of ribosomes from endoplasmic-reticulum membranes. No significant modifications occur in mitochondrial and plasma-membrane markers.
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PMID:Characterization of subcellular components in synchronized hepatoma cells as a function of the cell cycle. 57 39

Novikoff kepatoma microsomes catalyze the hydroxylation of benzphetamine and ethylmorphine at rates less than 1% of those of liver microsomes but catalyze the hydroxylation of p-nitroanisole and p-nitrophenetole at rates about 40% of those of liver microsomes. Benzo[a]pyrene hydroxylation is also catalyzed by Novikoff hepatoma microsomes at about 2% of the rate of liver microsomes. Like the hepatic microsomal system the rates of substrate hydroxylation by Novikoff hepatoma microsomes can be increased by pretreatment with phenobarbital/hydrocortisone or beta-naphthoflavone and inhibited by carbon monoxide, SKF-525A, and 7,8-benzoflavone. In addition, NADPH-cytochrome P-450 reductase (NADPH:ferricytochrome oxidoreductase, EC 1.6.2.4) has been partially purified from Novikoff hepatoma ascites cells and some properties are described. The induction and inhibition characteristics of the Novikoff hepatoma microsomal hydroxylation activities and the isolation of a cytochrome P-450 reductase from the hepatoma are consistent with the presence of a functional mixed function oxidase system in the Novikoff hepatoma, analogous to that present in liver endoplasmic reticulum.
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PMID:Drug metabolism in the Novikoff hepatoma: evidence for a mixed function oxidase system and partial purification of cytochrome P-450 reductase. 71 41

Transplantable rat liver tumors 5123 t.c., 7288 ct.c., 5123 t.c.(H) and the Novikoff hepatoma have active mixed function oxidase systems capable of metabolizing a variety of drug and polycyclic hydrocarbon substrates. The tumor drug metabolism systems are at best 20% as active as rat liver. The tumor drug metabolism activities are induced by pretreatment with phenobarbital or beta-naphthoflavone and can be inhibited with specific inhibitors such as carbon monoxide or 7,8-benzoflavone. Tumor drug metabolism systems appear to consist of cytochrome P-450 and cytochrome P-450 reductase. The properties of the two protein components from tumors are highly similar to the corresponding components of the liver drug metabolism system. Cytochrome P-450 reductase has been at least partially purified from the Novikoff hepatoma and hepatoma 5123 t.c.(H). The kinetic and physical properties of the tumor reductases are similar to those of the liver reductase except that the Km of hepatoma 5123 t.c.(H) reductase, but not of the Novikoff hepatoma reductase for NADPH, is elevated an order of magnitude over the Km of the liver reductase. The mechanism for the interaction of electron donor and electron acceptor with liver or tumor reductases seems to be a sequential reaction mechanism. Experiments on the NADP-inhibition of the interaction of NADPH and cytochrome c with liver reductase indicate that NADP is competitive with NADPH and noncompetitive with cytochrome c. This result is consistent with the postulate of a sequential reaction for NADPH-cytochrome P-450 reductases of liver and tumors. These data support the conclusions that an active drug metabolism system is present in liver tumors and that the tumor systems are constituted like the liver system.
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PMID:The drug metabolism systems of liver and liver tumors: a comparison of activities and characteristics. 74 99

NADPH cytochrome c (P-450) reductase was purified from human placental microsomes using a combination of affinity and gel filtration chromatography. Affinity chromatography using agarose-hexane-adenosine 2'5 diphosphate resulted in two protein bands being detected by SDS-PAGE of approximate MwS 68 and 75 kDa. Fractions containing the two proteins were pooled, and then resolved using Sephacryl S-200. Both of the purified proteins displayed enzyme activity, measured by their ability to reduce cytochrome c. The 75 kDa protein obtained was used to immunize three female New Zealand white rabbits. The IgG fraction was partly purified from rabbit sera which suppressed placental microsomal NADPH cytochrome c reductase activity by > 80% using 33% ammonium sulphate. The procured antibody suppressed androstenedione aromatase activity in microsomal preparations of human placental and breast adipose tissue, and NADPH cytochrome c reductase activity in prostate (benign and malignant), MDA-MB-231 breast cancer cells, breast adipose, Hep G2 hepatoma cells and placental microsomal preparations. The extent of NADPH cytochrome c reductase inhibition varied in the order of malignant prostate < benign prostate < MDA < breast adipose < Hep G2 < placenta. The results suggest that human placental NADPH cytochrome c (P-450) reductase shares common antigenic epitopes pertinent to its capability of reducing cytochrome c in all of the above-mentioned tissues. In attempting to associate possible changes in NADPH cytochrome c reductase activity imposed by neoplasia to the obtained immunochemical cross reactivity and enzyme activity results, it was noted that microsomes obtained from MDA cells exhibited enzyme activity significantly less than that of breast adipose microsomes (1.6 and 8.1 nmol/min/mg protein, respectively) and by comparison showed 6% less homology towards the placental antibody. The results obtained for benign and malignant prostate showed no significant difference between the neoplastic states as adjudged by enzyme activity and immunochemical assays.
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PMID:Immunochemical specificity of placental NADPH cytochrome c (P-450) reductase in neoplastic and non-neoplastic human tissue. 141 86

We analyzed lipids extracted from human hepatoma HepG2 cells using a high performance liquid chromatograph equipped with a reversed phase column and found a compound with a mass spectrum showing certain diagnostic ion fragments of 1-methoxy-5-polyprenyl-phenol, a known intermediate of ubiquinone biosynthesis. Universally radiolabeled [14C]-p-hydroxybenzoate, a precursor of ubiquinone, was incorporated into the compound on incubation with the cells, suggesting that the compound is a precursor of ubiquinone. The presence of the compound in the microsomal fraction of HepG2 cells was not due to contamination by the mitochondrial fraction because the activity of succinate-cytochrome c reductase in the microsomal fraction was below 1% of that in the mitochondrial fraction, whereas the contents of ubiquinone and the compound in the former were 4.6 and 7.8% of those in the latter, respectively. These results support the hypothesis that ubiquinone biosynthesis might occur in microsomes as well as mitochondria.
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PMID:An intermediate of ubiquinone biosynthesis exists in the microsomal fraction of HepG2 cells. 196 90

The tissues of hepatocellular carcinoma were operatively resected from six patients. All four components of the systems of microsomal cytochrome P-450-linked monooxygenase of the tissues were investigated and compared to those of normal liver tissue. The concentrations of cytochromes P-450, P-420 and b5 were measured optically and the concentrations of all components except cytochrome P-450 were measured by the Western blotting method followed by immunochemical staining. In microsomes of hepatocellular carcinoma tissues, there was as much cytochrome P-450 and other redox components as in the normal liver tissues, but cytochrome P-450 in liver cancer tissues was unstable and easily converted to cytochrome P-420. The specific activities of NADPH- and NADH-ferricyanide and cytochrome c reductase of each sample were also measured. In the microsomes of the cancer tissues, the specific activities were remarkably reduced compared with those of normal liver tissues. The lipid compositions of the microsomes and the phospholipid/cholesterol ratios (w/w) were 13.1 +/- 3.13 in the cancer tissues and 43.0 +/- 6.74 in normal liver tissues. This difference of the lipid composition elucidates the instability of cytochrome P-450 molecules and the inefficiency of the electron transport of cytochrome P-450-linked monooxygenase systems.
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PMID:Microsomal cytochrome P-450-linked monooxygenase systems and lipid composition of human hepatocellular carcinoma. 254 14


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