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

The effect of separate and combined administration of 15% ethanol and 0.2% CsCl solution on life span of rats with Novikoff hepatoma implants was studied as a function of time of initiation of treatment. Pretreatment with CsCl alone or combined with ethanol resulted in earlier onset on morbidity compared to the ethanol-treatment or to controls. As high as 87.5% of Cs-treated animals died 16 days post tumor implantation compared to 33% of rats receiving CsCl and ethanol combined. This protective action of ethanol against Cs-evoked toxicity in tumor-bearing rats persisted through the experiment. Animals subjected to drug treatment immediately after tumor transplantation displayed delayed onset of morbidity compared to drug pretreated rats. In both cases the Cs-treatment enhanced morbidity by approximately 2 folds from corresponding controls. Animals sacrificed 18 days post tumor inoculation showed an induction of hepatic alcohol dehydrogenase and an increase in Vmax without changes in the apparent Km by the Cs-treatment. There was an increase in liver mitochondrial aldehyde dehydrogenase of hepatoma-bearing rats from tumor-free controls which was associated with an increase in the apparent Km value. The results indicate potentiation of the hepatoma toxicity by CsCl which may be minimized by ethanol. A role for hepatic enzymes determined in the pathogenesis of tumor line studied and/or their use as a biochemical correlate is suggested.
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PMID:Effect of cesium and ethanol on tumor bearing rats. 639 34

The interrelationship between certain dehydrogenases and a hepatic tumor was studied in mice. A rapidly growing hepatoma, Novikoff hepatoma, was transplantable from rats to mice after serial passages in Sprague-Dawley albino mice. Mice inoculated with viable tumor cell suspension were sacrificed 14, 18, 21 or 34 days thereafter. Hepatic cytoplasmic and mitochondrial aldehyde dehydrogenase (ALDH) were measured in addition to liver alcohol dehydrogenase (ADH) and testicular ALDH. Hepatic cytoplasmic and mitochondrial ALDH were markedly inhibited from controls at all time periods studied. Likewise, testicular ALDH was inhibited from respective controls in Novikoff hepatoma-bearing mice. No changes were measurable in hepatic ADH of hepatoma-bearing mice. The enzyme kinetics studied show a reduction in Vmax and an alteration in the apparent Km 34 days after tumor inoculation. Further analyses of hepatic mitochondrial ALDH showed that the inhibition was similarly present in the enzyme with the low and the high Km property. The results suggest that changes in the specific activity and property of ALDH may be a useful tool as a biochemical concomitant to both development and progression of the hepatoma studied.
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PMID:Hepatic and testicular aldehyde dehydrogenase in tumor-bearing mice. 639 79

Well-differentiated Reuber H35 rat hepatoma cells in culture maintain a variety of biochemical functions characteristic of hepatocytes [Deschatrette, J., and M. C. Weiss. 1974. Biochimie. 56: 1603-1611]. To demonstrate the suitability of this system as a model for exploring mechanisms of ethanol hepatotoxicity, the following were investigated: 1) ethanol metabolism in whole cells and cell extracts and 2) effects of ethanol exposure on cellular lipid content. Cultures of H35 cells exposed to 10 mm ethanol metabolized the ethanol at rates similar to those reported in rat liver. Under these conditions, soluble alcohol dehydrogenase activity accounted for greater than 87% of total ethanol metabolism. H35 cells exposed to 240 mm ethanol for 3 days contained four times more triacylglycerol and cholesteryl ester than control cells. Total phospholipid and unesterified cholesterol levels were unaffected by ethanol. Neutral lipid content of Chinese hamster ovary cells was unchanged after ethanol exposure. The increased triacylglycerol content of ethanol-treated H35 cells appeared to result from an accelerated rate of conversion of long chain fatty acids into triacylglycerol. Several lines of evidence indicated that alcohol dehydrogenase-mediated ethanol oxidation was critical in promoting increased triacylglycerol content of cultured cells. Since 240 mm ethanol blocked cellular proliferation, long term effects of ethanol were studied at a level of 10 mm, which allowed a nearly normal growth rate. After 7 weeks of continuous exposure, 10 mm ethanol-treated H35 cells contained five times more triacylglycerol than paired controls. The well-differentiated H35 cell appears to be an excellent in vitro model system for studying both short-term and long-term effects of ethanol on liver cells.-Polokoff, M. A., M. Iwahashi, and F. R. Simon. Ethanol treatment increases triacylglycerol and cholesteryl ester content of cultured hepatoma cells.
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PMID:Ethanol treatment increases triacylglycerol and cholesteryl ester content of cultured hepatoma cells. 663 Dec 31

Dedifferentiated rat hepatoma variant cells of clone Faof1 fail to express most of the liver-specific functions characteristic of its line or origin, H4IIEC3. When Faof1 cells are cultivated for 48 hr in the form of aggregates two cell types can be recovered from monolayer cultures established from the aggregates: the majority of cells are similar to the Faof1 parental line, but a new cell type (designated dag) that adheres only weakly to the substrate is present at a frequency of 2--12 X 10(-2). Eight dag populations and eight clones are characterized as being different from Faof1 cells by the production of serum albumin, aldolase B and in some cases activity of alcohol dehydrogenase and alanine aminotransferase. No dag cells are recovered after 18 or 24 hours of aggregation, but after 48 or 96 hrs 1--5% of the cells give rise to clones of dag cells. During aggregation cells are committed to become dag cells but their new phenotype is expressed only after 5--12 days. The fraction of dag cells in colonies that grow out from aggregates suggests that dag transformation is not a clonal event. These experiments demonstrate that a transitory change in the culture conditions of Faof1 cells can lead to a heritable modification in phenotypic expression. Since dag cells fail to express the liver-specific gluconeogenic enzymes that permit cells to grow in glucose-free medium, it is possible to select from dag populations revertants in which expression of these activities is restored. The frequency of appearance of such dag revertants is not increased by the action of EMS.
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PMID:Dedifferentiated variants of a rat hepatoma: partial reversion induced by cell aggregation. 744 71

Aldose reductase and aldehyde reductase are members of the aldo-keto reductase superfamily, and participate in the reduction of a wide range of carbonyl compounds. We have purified aldose reductase from rat lens and raised antiserum against it in rabbits. Immunoblot analyses using this antibody showed that a significant amount of aldose reductase was expressed in cell lines derived from hepatomas while it was negligible in normal hepatocytes. Elevated expression of aldose reductase was also observed in cancerous lesions of 3'-methyl-4-dimethyl-aminoazobenzene (3'-Me-DAB)-induced hepatocarcinomas. Expression of aldose reductase mRNA was confirmed in these cells by Northern-blot analysis, suggesting that the induction occurred at the stage of gene transcription. The level of aldehyde reductase, however, did not change in cancerous tissue or in the cell lines. The viability of hepatoma cells in the presence of 3-deoxyglucosone and glyceraldehyde was decreased by an aldose reductase inhibitor, ONO-2235 (5-[1Z,2E)-2-methyl-3-phenylpropenylidene]-4-oxo-2-thioxo -3- thiazolidineacetic acid). Taken together, induction of aldose reductase gene expression during hepatocarcinogenesis may render cancer cells resistant to various toxic carbonyl compounds produced during metabolism or administered as anti-cancer drugs.
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PMID:Elevation of aldose reductase gene expression in rat primary hepatoma and hepatoma cell lines: implication in detoxification of cytotoxic aldehydes. 755 25

Hepatocytes cultured for extended periods of time lose the ability to express alcohol dehydrogenase and thus, the ability to efficiently oxidize ethanol. Therefore, it has been difficult to investigate the effects of chronic ethanol oxidation by hepatocytes in vitro. To circumvent this problem, we have inserted the coding region of an exogenous alcohol dehydrogenase gene into an hepatic cell line. Using the human hepatocellular carcinoma cell line, Hep G2, we have constructed an hepatic cell line that stably expresses alcohol dehydrogenase. These recombinant cells, termed HAD 73.1 cells, express approximately 40% of the alcohol dehydrogenase activity of freshly isolated rat hepatocytes. When the ethanol metabolizing ability of these cells was directly measured, the results indicated that not only were these cells able to metabolize ethanol at approximately 70% of the rate of freshly isolated rat hepatocytes but acetaldehyde concentrations of up to 50 microM were detected in the medium. Furthermore, the level of acetaldehyde produced during ethanol oxidation was augmented by cyanamide, an inhibitor of acetaldehyde oxidation, while the ability of these cells to metabolize ethanol was inhibited by pyrazole, an inhibitor of alcohol dehydrogenase. These results suggest that this in vitro system will be a valuable tool enabling detailed biochemical studies exploring the effects of chronic ethanol oxidation on the liver and the mechanisms of alcohol-induced hepatic cell injury.
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PMID:Establishment of a recombinant hepatic cell line stably expressing alcohol dehydrogenase. 764 56

The mouse alcohol dehydrogenase gene Adh-1 contains an unusually long alternating purine-pyrimidine sequence within its first intron. This alternating sequence differs in length between strains that differ in the extent of Adh-1 expression, and it has been suggested that it plays a role in gene expression. We demonstrate that this alternating sequence can form Z-DNA in vitro. The alternating sequence can act as a positive regulatory element in transient transfection assays in hepatoma cell lines, but not in CV-1 (monkey kidney) cells, suggesting that it can act as a tissue-specific regulatory element. Nuclear run-on experiments showed that the differential expression of Adh-1 from high- and low-activity strains is, however, controlled at the post-transcription level.
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PMID:Structure and function of a long alternating purine-pyrimidine sequence in the mouse alcohol dehydrogenase Adh-1 gene. 784 Jun 44

The Long-Evans Cinnamon (LEC) rat is a mutant strain established from Long-Evans rats. LEC rats display hereditary hepatitis and spontaneous hepatocellular carcinoma (HCC). We first tried to examine effects of ethanol consumption on the development of HCC, and fed a Lieber's liquid diet containing 5% ethanol to LEC rats. However the rats died within 2 weeks because of acute alcohol intoxication. In LEC rats, the concentration of ethanol and acetaldehyde in blood was significantly higher, and liver alcohol dehydrogenase activity was slightly lower and acetaldehyde dehydrogenase activities were remarkably suppressed compared to those of Wistar rats. These results suggest that LEC rats have hereditary deficiencies of ethanol and acetaldehyde metabolizing enzymes.
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PMID:Abnormal ethanol metabolism in Long-Evans Cinnamon rats, a mutant strain developing spontaneous hepatoma. 800 22

It is well established that many types of tumor cells have reduced lipid peroxidation capacity compared to their normal counterparts. Changes in the activity of enzymes metabolizing aldehydes produced by lipid peroxidation have also been reported in a variety of tumor cells. We have investigated the relationship between changes in lipid peroxidation and changes in aldehyde-metabolizing enzymes in normal hepatocytes and two representative rat hepatoma cell lines, McA-RH-7777 and JM2. Compared to hepatocytes, both 7777 and JM2 cells have significantly lower basal and prooxidant-induced levels of lipid peroxidation than normal hepatocytes. Using 4-hydroxynonenal (4-HNE) as substrate, both cell lines also have significantly reduced activities of alcohol dehydrogenase (ADH) and glutathione S-transferase (GST) compared to hepatocytes. JM2 cells have significantly increased aldehyde dehydrogenase (ALDH) and aldehyde reductase (ALRD) activities with 4-HNE. In 7777 cells the ALDH and ALRD activities are not different from hepatocytes. The changes in enzyme activity are inversely correlated with the sensitivity of cells to 4-HNE. JM2 cells, with increased ALDH and ALRD and decreased ADH and GST, are much more resistant to the toxic effects of 4-HNE than 7777 cells. Normal hepatocytes and JM2 cells are approximately equally resistant to 4-HNE even though hepatocytes rely primarily on GST-mediated aldehyde conjugation to metabolize 4-HNE. Coupled with previous results from our laboratories, the overall increased sensitivity of certain hepatoma cells to lipid aldehydes appears due to decreased ability of these hepatoma cells to remove toxic products of lipid peroxidation. Moreover, hepatoma cells with increased levels of aldehyde dehydrogenase and aldehyde reductase appear most like hepatocytes in their ability to metabolize lipid aldehydes.
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PMID:Role of aldehyde metabolizing enzymes in mediating effects of aldehyde products of lipid peroxidation in liver cells. 803 12

The human alcohol dehydrogenase gene ADH2 is expressed at high levels in liver, at lower levels in kidney and several other tissues, and is not expressed in other tissues such as spleen. This pattern of expression suggests a complex regulatory region that responds to a variety of transcription factors in different cellular contexts. Seven cis-acting sequences in the proximal 271 bp of the ADH2 promoter were mapped. The occupancy of these sites differed markedly among extracts from liver, kidney, spleen, H4IIE-C3 cells, HeLa cells, and CV-1 cells. These differences in occupancy were accompanied by differences in gene expression in the three cell lines. The ADH2 promoter directed substantial CAT expression in H4IIE-C3 cells (rat hepatoma) and in HeLa cells, but only minimal expression in CV-1 cells (monkey kidney fibroblasts). The three cell lines differed in the effects of deletions within the promoter. An ADH2 promoter that contained both the USF/MLTF site and the G3T site gave four- to eight-fold higher expression in both H4IIE-C3 and HeLa cells than a smaller promoter that lacked these sites; in contrast, these sequences did not significantly stimulate transcription in CV-1 cells. A CTF/NF-I-related site acted as a negative element in all three cell lines. Coexpression of C/EBP alpha altered the cell specificity. The ADH2 promoter was moderately stimulated (two-fold) by coexpression of C/EBP alpha in H4IIE-C3 cells, but markedly stimulated in HeLa cells and in CV-1 cells (11- and 20-fold, respectively). These results demonstrate the differential importance of cis-acting sequences and of specific transcription factors in different cells, which allows regulated expression of ADH2 in multiple tissues.
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PMID:Tissue-specific differences in the expression of the human ADH2 alcohol dehydrogenase gene and in binding of factors to cis-acting elements in its promoter. 817 54


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