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)

Rodent cells were found to contain a high level of alcohol dehydrogenase activity which was not inducible. Other hepatoma and nonhepatoma cell lines were tested and found to contain lower but measurable levels of alcohol dehydrogenase.
J Stud Alcohol 1976 Mar
PMID:Viability of cells in ethanol. Role of alcohol dehydrogenase. 0 66

The initial rates of transport of uridine, thymidien, purines, choline and 2-deoxy-D-glucose by cultured Novikoff rat hepatoma cells were determined as a function of temperature between 5 and 41 degrees C. Arrhenius plots of all transport systems exhibited sharp breaks in slope; between 17 and 23 degrees for uridine, thymidine and hypoxanthine-guanine transport and between 29 and 32 degrees for choline and 2-deoxy-D-glucose transport. The activation energies for the transport systems changed from 15-26 kcal/mole below the transition temperatures to 4-9 kcal/mole above the transition temperatures. Propagation of the cells in the presence of cis-6-octadecenoic acid which results in marked changes in the lipid composition of cell membrane, had little effect on the temperature characteristics of the various transport systems. Similarly, propagation of the cells for 24 hr in media containing Tween 40 or nystatin had no effect on the capacity of the cells to transport the various substrates or on the temperature dependence of the transport systems. The presence of ethanol, phenethyl alcohol or Persantin at concentrations that inhibited thymidine and 2-deoxy-D-glucose transport between 40 and 70% also did not alter the transition temperatures or activation energies for the transport of these substrates. Cytochalasin B, on the other hand, shifted the transition temperature for 2-deoxy-D-glucose transport to higher temperatures in a concentration-dependent manner, whereas it had no effect on the temperature dependence of thymidien transport.
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PMID:Temperature-dependent changes in activation energies of the transport systems for nucleosides, choline and deoxyglucose of cultured Novikoff rat hepatoma cells and effects of cytochalasin B and lipid solvents. 5 43

The alpha-fetoprotein (AFP) and albumin localization were studied in the cells of rat Zaidel's ascitic hepatoma. It was shown in the paraffine sections of the hepatoma cells fixed by mixture of 96 degrees ethanol with 1% glacial acetic acid that 9.3% of hepatoma cells contained AFP and 0.6% of the cells--serum albumin. Small quantities of the tumour cells had both of these proteins simultaneously. There was no definite regularity in the distribution of the AFP and albumin-containing cells in the tumour islands.
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PMID:[Distribution of alpha-fetoprotein and albumin in paraffin sections of cells of Zaidel's ascitic hepatoma]. 5 59

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

Significant liver disease including fatty metamorphosis, alcoholic hepatitis, cirrhosis, and hepatoma occur in two thirds of subjects who consume alcoholic beverages in sufficient quantities to interfere with work and social responsibilities; this is of major importance in the rapidly escalating morbidity and mortality from alcoholism. Chronic alcoholics should be routinely evaluated for the presence of altered liver function and structure. Clearance of indocyanine green using dichromatic ear densitometry and computer and analysis provides a simple and sensitive method for mass screening of such patients. Clinical studies of lymphocyte reactivity to purified alcoholic hyaline may be valuable in recognizing alcoholic hepatitis, the precursor of cirrhosis. Ethanol toxicity, malnutrition and constitutional factors contribute to the development of hepatic fibrosis and cirrhosis in alcoholics. Ethanol and/or acetaldehyde and the supernatant from lymphocytes stimulated by alcoholic hyaline cause a significant increase in the incorporation of proline into collagen of the damaged liver. Abstinence and correction of nutrient deficits are the cornerstones of treatment for alcoholic liver disease; a daily meal and dietary supplements should be provided for those with liver injury who continue to imbibe. Alcoholics with progressive liver disease despite supportive therapy may be aided by pharmacologic agents which suppress immunologic response and reduce fibrogenesis.
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PMID:Liver disease of the alcoholic. 16 41

Steroid metabolism in hepatoma tissue culture (HTC) cells derived from a male rat was investigated. Steroids in ethanol were incubated with the cells for various lengths of time. Volume of ethanol never exceeded 1% of incubation volume. Thin-layer and paper chromatography were used. Incubation was with tritiated steroids. It was demonstrated that testosterone as well as dihydrotestosterone is transformed. The main enzyme activities detected were 5alpha-reduction and 3alpha-, 3beta, and 17beta-hydroxysteroid dehydrogenation. The pattern of metabolism was reproducible and varied with time, substrate concentration, and number of cells incubated. Some steroids interfered with androgen metabolism. 17beta-estradiol, 17-epitestosterone, and progesterone competed for the 17beta-hydroxyprogesterone dehydrogenase. it is concluded that 3beta and 17beta reduction in the HTC cells may be catalyzed by the same enzyme which might differ considerably from the 3beta-hydroxysteroid dehydrogenase assayed in intact liver cells. A hepatoma derived from a female rat also produced considerable amounts of 3beta-derivatives of testosterone.
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PMID:Metabolism of testosterone and dihydrotestosterone in cultured rat hepatoma cells. 17 19

A dose of 10 or 20 mg of N-butylnitrosourea (BNU) dissolved in 50% ethanol was administered by a gastric tube to 6-week-old male ICR/JCL strain mice and they were sacrificed 15 months later. One of 18 animals developed a hepatoma, but none of the mice given CCl4 in 0.1 ml of 50% oliver oil subcutaneously at the right thigh developed hepatoma. However, a marked enhancement of hepatoma induction was observed in mice injected with CCl4 one day before the single intragastric administration of BNU, with 12 out of 28 mice developing one or more hepatomas (average 3.2/mouse) ranging in diameter from 0.5 to 1.5 cm. By extending the administration interval between CCl4 and BNU to 1 week or 1 month, or by reversing the order of administration, the hepatotumorigenic action was virtually lost. There was no occurrence of hepatoma but a predominant development of leukemia, of either thymic or nonthymic origin, was observed in mice of younger age treated with CCl4 one day before continuous oral administration of BNU (1 mg/day/mouse). It is thus concluded that the preparative (cocarcinogenic) action of CCl4 is indispensable for hepatotumorigenesis with a single large dose of BNU.
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PMID:Preparative action of carbon tetrachloride in liver tumorigenesis by a single application of N-butylnitrosourea in male ICR/JCL strain mice. 17 59

It was previously reported that the properties of alcohol dehydrogenase of a rat hepatocellular carcinoma (Becker H-252), a tumor of intermediate growth rate, were different from those of the liver enzyme, suggesting different isozymes. To determine whether the degree of differentiation affected the isozyme of alcohol dehydrogenase, a fast-growing, poorly differentiated tumor and one that is well differentiated and of intermediate growth rate were studied. Alcohol dehydrogenase from Morris hepatoma 7288ctc, a fast-growing, poorly differentiated tumor, had properties similar to those found with the Becker-H-252 tumor, including a high Km for ethanol and acetaldehyde and the absence of substrate inhibition. By contrast, alcohol dehydrogenase from the well-differentiated Morris hepatoma 5123C had properties similar to those of the liver enzyme. Thus, alcohol dehydrogenase is another example of an enzyme the isozyme composition of which changes with neoplastic de-differentiation. Further studies, including gel electrophoresis, substrate specificity patterns, and interaction with antibodies to alcohol dehydrogenase, are required to determine the factors responsible for the biochemical defect that occurs at the molecular level during carcinogenesis and whether the alcohol dehydrogenase isozymes in the Becker H-252 and Morris 7288ctc hepatomas are identical. A survey of several normal rat tissues revealed that only the stomach contains this unique isozyme of alcohol dehydrogenase.
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PMID:Kinetic properties of alcohol dehydrogenase in hepatocellular carcinoma and normal tissues of rat. 17

Deoxyribonucleic acid polymerase-beta (EC 2.7.7.7) FROM THE Novikoff hepatoma has been purified over 200 000-fold (based on the increase in specific activity), by ammonium sulfate fractionation and chromatography on DEAE-Sephadex, phosphocellulose, hydroxylapatite, and DNA-cellulose. The enzyme is remarkably stable through all stages of purification until DNA-cellulose chromatography when it must be kept in buffers containing 0.5 M NaCl and 1 mg/ml bovine serum albumin for stability. The enzyme appears to be homogeneous as evidenced by a single stainable band when subjected to electrophoresis in polyacrylamide gels of different porosity. The stainable band corresponds to the DNA polymerase as determined by slicing sister gels and assaying for enzyme activity. The specific activity of the homogeneous preparation is about 60 000 units/mg. The enzyme lacks detectable exonuclease or endonuclease activity. It has a molecular weight of 32 000 as determined by sodium dodecylsulfate-polyacrylamide gel electrophoresis. In sucrose gradients, the molecular weight is estimated at 31 000. The isoelectric point of the hydroxylapatite fraction enzyme is 8.5. The Novikoff beta-polymerase requires all four deoxyribonucleoside triphosphates, primer-template, and a divalent cation for maximal activity. The apparent Km for total deoxyribonucleoside triphosphate is 7-8 muM and for DNA 125 mug/ml. Activated DNA, rendered 7% acid soluble by DNase I, is the preferred primer-template, although a number of synthetic polynucleotides can by efficiently utilized, particularly in the presence of Mm2+ optimum is 7 mM; the Mn2+ optimum is 1 mM. The pH optimum is 8.4 in Tris-HCl or 9.2 in glycine buffer. The beta-polymerase is sstimulated about twofold by NaCl or KCl at an optimum of 50-100 MM, and the enzyme maintains considerable activity at high ionic strengths. The DNA polymerase is inhibited by ethanol, acetone, and a variety of known polymerase inhibitors. Glycols stimulate the enzyme as does spermine or spermidine. Unlike most beta-polymerases, the Novikoff enzyme is moderately sensitive to N-ethylmaleimide.
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PMID:Novikoff hepatoma deoxyribonucleic acid polymerase. Purification and properties of a homogeneous beta polymerase. 18 3

The metabolism of 2-deoxy-D-galactose has been studied in AS-30D rat ascites hepatoma cells in suspension. Using 2-deoxy-D-(1-14C)galactose and an alkaline ethanol deproteinization procedure, the quantitatively identified metabolites included 2-deoxy-D-galactose 1-phosphate comprising 99.3%, and UDP-2-deoxy-D-galactose and UDP-2-deoxy-D-glucose, together amounting to 0.4% of the total metabolites. After incubation for 5 h in the presence of 2-deoxy-D-galactose (1 mmo1/1), the content of 2-deoxy-D-galactose 1-phosphate reached 35 mmo1x(kg cells)-1. The rate of phosphorylation of 2-deoxy-D-galactose was rapid during the first 30 min and decreased to approximately 20% of this rate during the subsequent hours. The rapid trapping of Pi in the form of 2-deoxy-D-galactose 1-phosphate resulted in a depression of free intracellular Pi in spite of a concomitant increase in net 32Pi uptake from the medium and a decrease of ATP and other 5'-nucleotides. The rates of glucose utilization and lactate production were depressed by more than 80% in the presence of 2-deoxy-D-galactose (1 mmo1/1). Interruption of Pi trapping by removal of 2-deoxy-D-galactose from the medium reversed the depressions of Pi and ATP and resulted in a rapid but incomplete relief of glycolysis inhibition. Crossover analysis of glycolytic intermediates indicated an inhibition at the 6-phosphofructokinase step. The depression of glucose utilization may be mediated by the increased level of glucose 6-phosphate, a potent inhibitor of hexokinase. An additional inhibitory effect of a metabolite of 2-deoxy-D-galactose at the 6-phosphofructokinase step was indicated by crossover analysis after reversal of Pi and ATP depressions in the presence of a high intracellular content of 2-deoxy-D-glactose 1-phosphate. The quantitative analysis of the metabolites of 2-deoxy-D-galactose demonstrated the predominance of the monophosphate and the negligible formation of UPD derivatives of this sugar analog in AS-30D hepatoma cells. This provides a system for the investigation of a galactose analog as a phosphate-trapping agent in the virtual absence of uridylate trapping.
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PMID:2-Deoxy-D-galactose metabolism in ascites hepatoma cells results in phosphate trapping and glycolysis inhibition. 19 12


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