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)

Twelve adults with hepatocellular carcinoma (HCC) and 8 individuals with histologically normal liver, were measured for serum selenium concentration and glutathione peroxidase (GSH-Px) of liver tissue. It was found a reduced serum selenium and liver GSH-Px in patients with HCC. Serum selenium concentration and the enzyme activity were positively correlated (p less than 0.01). The increased risk of carcinoma in selenium deficiency may be partially due to a reduced activity of GSH-Px, one of the most important scavenger enzymes of oxygen toxic radicals.
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PMID:Reduction of liver glutathione peroxidase activity and deficiency of serum selenium in patients with hepatocellular carcinoma. 302 33

The importance of some glutathione metabolic pathways was examined in two highly dedifferentiated hepatomas, Yoshida AH-130 and Morris 3924 A hepatomas, and in normal liver in relation to their role against oxidative stress. The cytosol prepared from Yoshida hepatoma cells decreased the peroxidation rate in normal liver microsomes and mitochondria, but this antioxidant property was not displayed by Morris hepatoma. Glutathione peroxidase and glutathione-S-transferases activities were extremely low in both hepatomas; glutathione reductase activity values were about half the normal liver values. The large decrease in glutathione peroxidase and glutathione-S-transferases suggests that in these two tumors only small amounts of GSH can be used in reduction or conjugation reactions, such as the reduction of hydrogen peroxide and lipid hydroperoxides or the conjugation of GSH with the end products of lipoperoxidation, aldehydes or ketones. The hypothesis of a more efficient GSSG reduction in hepatomas, due to the low glutathione peroxidase/glutathione reductase activity ratio, is also discussed. The described changes in glutathione related enzymes do not seem to have any correlation with the protective effect against the lipoperoxidative processes displayed by some tumors since these enzymatic activities were similar in both hepatomas whereas only Yoshida hepatoma showed antioxidant properties.
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PMID:Analysis of glutathione-dependent enzyme activities in two different rat hepatomas and in normal liver in relation to their role in resistance to oxidative stress. 323 5

A large proportion of the metabolites formed from benzo[a]pyrene (BP) in cell cultures from rodents, fish and humans result from conjugation of an oxidized metabolite of BP with sulfate, glucuronic acid or glutathione (GSH). To improve the analysis of these metabolites, a reversed-phase ion-pair h.p.l.c. system using a step gradient of methanol:tetrabutyl-ammonium bromide in ammonium formate buffer has been developed for the separation of these three classes of conjugates. This system separated 3-hydroxy-BP glucuronide and sulfate conjugates and resolved them from GSH conjugates of BP 4,5-oxide, 7,8-oxide and 7,8-diol-9,10-epoxide. Cultures of early passage Syrian hamster, Wistar rat and Sencar mouse embryo cells, a bluegill fry (BF-2) cell line and a human hepatoma cell line (HepG2) were exposed to [3H]BP for 24 h. Medium samples from each were extracted with chloroform: methanol:water, and the water-soluble metabolites were analyzed by ion-pair h.p.l.c. The largest peak of metabolites in the media from cell cultures from rodents and the bluegill fry cell line co-eluted with the glucuronic acid conjugate of 3-hydroxy-BP. These phenol-glucuronides represented 48-62% of the total water-soluble metabolites in the fish and rodent cell cultures. Treatment of this material with beta-glucuronidase released 3-hydroxy-BP and 9-hydroxy-BP in ratios from 3:4 to 13.3:1 in various cultures. Media from the bluegill fry cell line and the mouse embryo cell cultures also contained a peak of BP-diol glucuronides; treatment of these peaks with beta-glucuronidase released mainly BP-7,8-diol. In HepG2 cells, 40% of the water-soluble metabolites were identified as sulfate conjugates of 3-hydroxy-BP and 9-hydroxy-BP. No glucuronic acid conjugates of BP metabolites were detected in HepG2 cells. Only small amounts of the water-soluble metabolites from these cell cultures eluted in the same volumes as the synthetic GSH conjugate of BP-4,5-oxide, BP-7,8-oxide and BP-7,8-diol-9,10-oxide. These studies indicate that conjugation with glucuronic acid represents a major pathway of formation of water-soluble metabolites from BP in cells derived from a number of species and demonstrate the value of this ion-pair h.p.l.c. system for the analysis of conjugates formed from BP.
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PMID:Separation by ion-pair high-performance liquid chromatography of the glucuronide, sulfate and glutathione conjugates formed from benzo[a]pyrene in cell cultures from rodents, fish and humans. 380 96

A 20 h pre-treatment of human cells from normal (foetal lung) or malignant origin (glioma, lines U118 MG and U251 MG and bladder carcinoma, line EJ) with dexamethasone failed to increase their radiation resistance in vitro despite a 2-fold increase in the GSH content of a glioma cell line, U251 MG, and a small but significant increase in the GSH content of EJ bladder carcinoma cells. In contrast, there was a correlation between an increase in radiation resistance and an elevated GSH content of rodent cells (Chinese hamster lung, line V-79-379A; ovary, line CHO; rat hepatoma, line HTC, and mouse neuroblastoma, line NB413A) after a similar pre-treatment. The results suggest that enhancement of radiation resistance cannot be directly ascribed to an elevated GSH content in steroid-treated cells. On the basis of these data it is unlikely that the efficacy of radiotherapy will be diminished amongst patients receiving concomitant treatment with dexamethasone. However, in vivo testing is required to confirm these findings.
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PMID:Studies on the relationship between the radiation resistance and glutathione content of human and rodent cells after treatment with dexamethasone in vitro. 387 26

A polypeptide of Mr 26,000 and pI 6.7 that was markedly increased in rat livers bearing hyperplastic nodules (HNs) induced by chemical carcinogens was identified immunochemically as the subunit of neutral glutathione (GSH) transferase (GSHTase; RX:glutathione R-transferase, EC 2.5.1.18; also called GSH S-transferase) purified from placenta (GSHTase-P) and was demonstrated immunohistochemically to be localized in preneoplastic foci and HNs. In the present study, GSHTase-P has been purified from the HN-bearing liver, and the distribution and inducibility have been examined quantitatively using anti-GSHTase-P antibody. Elevation of GSHTase-P in the HN-bearing livers was also confirmed by in vitro translation of mRNAs isolated from the HN-bearing livers. The purified GSHTase-P was homogeneous in size but had two charge isomers on two-dimensional gel electrophoresis. In normal tissues, including liver, placenta, and fetal liver, the protein content of GSHTase-P was generally low but was significantly high in kidney and pancreas. In contrast, the amount of GSHTase-P in HN-bearing livers (primary hepatomas) and transplantable Morris hepatoma 5123D were several 10-fold higher than that in normal liver but were undetectably low in transplantable Yoshida ascites hepatoma AH 130. Different from ordinary drug-metabolizing enzymes, GSHTase-P was uninducible by administration of drugs and carcinogens prior to appearance of the preneoplastic foci and HNs. In addition, species specificity of GSHTase-P was low as it was crossreactive among rat, hamster, and human.
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PMID:Purification, induction, and distribution of placental glutathione transferase: a new marker enzyme for preneoplastic cells in the rat chemical hepatocarcinogenesis. 392 85

Succinylacetone (SA) (4,6-dioxoheptanoic acid) is an abnormal metabolite produced in patients with hereditary tyrosinemia as a consequence of an inherited deficiency of fumaryl acetoacetate hydrolase activity. Patients with this disease are associated with a number of abnormalities, including aminoaciduria, proteinuria, liver failure, commonly hepatoma, and decreased GSH concentration in the liver. In the course of our studies of tyrosinemia, we found that the urine of patients with this disorder contains material(s) that absorbs light at 315 nm. We investigated the nature of the 315 nm material in detail. SA was found to react with amino acids and protein nonenzymatically, to form stable adducts at physiological temperature and pH. All SA adducts with amino acids and/or proteins exhibited an absorption peak at 315 nm. Although all amino acids reacted with SA, the most reactive amino acid was lysine (Lys), followed, in order, by glycine, methionine, phenylalanine, serine, alanine, and glutamine. SA-adducts were unstable at pH below 6, while they were made considerably more stable after reduction with NaBH4, suggesting that SA forms an adduct via Schiff base formation. High-performance liquid chromatography (HPLC) analysis of urines from patients with tyrosinemia revealed the existence of SA-glycine, SA-methionine, SA-tyrosine, and SA-phenylalanine. After digestion of urines with proteinase K, three more HPLC peaks appeared, which all corresponded to SA-Lys adducts. TLC analysis of SA-Lys showed that SA-Lys could form as many as seven different adducts. No SA-adduct peaks were observed in HPLC in urines from normal subjects, patients with other forms of aminoaciduria, or patients with the nephrotic syndrome. In addition to amino acids and proteins, SA reacted with reduced glutathione (GSH) and formed a stable adduct. These findings suggest that SA adduct formation with amino acids, GSH, and proteins is a significant process occurring in tyrosinemia, and may account for certain of the pathologic findings in this hereditary disorder.
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PMID:Hereditary tyrosinemia. Formation of succinylacetone-amino acid adducts. 392 1

A glutathione conjugate of aflatoxin B1 (AFB1) which has previously been identified as 8,9-dihydro-8-(S-glutathionyl)-9-hydroxy aflatoxin B1 (AFB1-GSH) (E.J. Moss, D.J. Judah, M. Przybylski and G.E. Neal, Biochem. J., 210 (1983) 227-233) has been degraded in vitro to all of the intermediates of the mercapturic acid pathway (MAP) and the chromatographic and spectral characteristics of each of these compounds investigated. The cysteinylglycyl conjugate (AFB1-Cys.Gly) was prepared by incubating the AFB1-GSH conjugate with a rat hepatoma cell line rich in gamma-glutamyl-transpeptidase (GGT). Incubations of the AFB1-Cys.Gly conjugate with dipeptidase produced a metabolite, which was purified and characterized by 1H-NMR spectroscopy as 8,9-dihydro-8-(S-cysteinyl)-9-hydroxy aflatoxin B1 (AFB1-Cys). The N-acetyl derivative of the AFB1-Cys conjugate resulted from the incubation of the AFB1-GSH conjugate in vitro with isolated rat kidney cells. Mass spectral data were consistent with the compound being 8,9-dihydro-8-(S-cysteinyl-(N-acetyl))-9-hydroxy aflatoxin B1 (AFB1-Nac.Cys). A chromatographically identical compound was obtained by the chemical acetylation of AFB1-Cys.
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PMID:The mercapturic acid pathway metabolites of a glutathione conjugate of aflatoxin B1. 393 41

Total homogenates from liver tissues, as well from Morris 3924 A and Yoshida AH-I30 hepatomas display a different degree of thiobarbituric acid reacting substances (TBArs) when incubated "in vitro". It is well known that carbonyl compounds arising from lipoperoxidative decomposition of unsaturated fatty acids can easily react with reduced glutathione (GSH). So, the decay in GSH we have shown in previous experiments could be accounted for GSH trapping by the formed aldehydes. Some discrepancies were, however, seen when the decay in GSH and the increase in GSSG were compared, both in normal and in tumour tissues. It is known that GSH can be destroyed not only through oxidative process, but also through the action of gamma-glutamyl-transpeptidase. In the present paper the decrease of total (TG) and reduced (GSH) glutathione was followed and compared with both the increase in GSSG and the increase in the production of TBArs, during "in vitro" incubation. In normal liver, increase in TBArs production parallels the decay in GSH concentration; GSSG, on the contrary, increases. In AH-I30 Yoshida hepatoma cells, TBArs production is lower and GSSG is also decreased. In 3924 A Morris hepatoma GSH decrease is similar to that observed in the liver, while TBArs production is lower and GSSG is also decreased. Analysis of TG content during the incubation-time suggests that GSH decay in both hepatoma types is essentially due to gamma-glutamyl-transpeptidase action, whilst GSH oxidation to GSSG is decreased.
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PMID:[Differences in glutathione oxidation and transpeptidylation between normal liver and hepatomas (author's transl)]. 612 64

Lipid peroxidation rate in four different hepatomas is quite different and seems to be related to their degree of deviation, low deviation tumours displaying higher peroxidative ability. Moreover, the supernatant of the highly anaplastic Yoshida hepatoma is able to decrease the peroxidation rate in normal liver microsomes. This antioxidant ability is not dependent upon an increased level of glutathione. The concentration of reduced glutathione (GSH) declines strongly during incubation in conditions favouring lipid peroxidation. Unlike normal liver homogenates, this decline of GSH in hepatomas is not due to the transformation of GSH into oxidized glutathione (GSSG) but mostly to the increased activity of the gamma-glutamyl-transpeptidase pathway.
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PMID:Lipid peroxidation in hepatomas of different degrees of deviation. 614 7

Qualitative and quantitative changes in glutathione S-transferase (GSH-T) were studied in human hepatocellular carcinoma. GSH-T specific activity (mumoles per min per mg protein) was variably reduced in hepatocellular carcinoma. Similar changes were seen in "cationic" GSH-T (ligandin) concentration determined by radioimmunoassay. Immunohistochemical studies with antihuman liver ligandin suggest that positive staining was more frequently found in well-differentiated tumors. The relative activities of "cationic," "neutral," and "anionic" transferases (pI greater than 7.5) activity ranged from virtually absent to near normal values. "Neutral" (pI 6 to 6.5) and "anionic" (pI less than 5.4) species were present more often in tumors than in normal liver. In two cases, normal liver tissue and tumor were obtained from the same patient. In one, only quantitative differences were present, while in the other "cationic" and "neutral" GSH-Ts were present in the normal liver tissue while both "cationic" and "anionic" species were found in the tumor. Our studies indicate that qualitative as well as quantitative changes of GSH-T occur in human hepatocellular carcinoma.
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PMID:Glutathione S-transferase in human hepatocellular carcinoma. 618 52


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