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)

Dihydrodiol dehydrogenase(s) (DD) have been implicated in the detoxication of proximate (trans-dihydrodiol) and ultimate carcinogenic (anti-diol-epoxide) metabolites of polycyclic aromatic hydrocarbons (PAHs). These activities are catalyzed by soluble hydroxysteroid dehydrogenases and/or by aldehyde reductases. Molecular cloning indicates tha these enzymes have a high degree of sequence identity with members of the aldo-keto reductase super family. Substrate specificity studies indicate that non-K-region trans-dihydrodiols are the preferred substrates and that anti-dio-epoxides are not oxidized by the enzyme. The products of the DD reaction are transient catechols which auto-oxidize to PAH-o-quinones. As a consequence of this auto-oxidation superoxide anion, hydrogen peroxide and semiquinone radicals are generated. Studies on the biotransformation of (+/-)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene indicate that in subcellular fractions from uninduced rat liver, DD plays a significant role in the metabolism of this proximate carcinogen. Thus, the formation of benzo[a]pyrene-7,8-dione is only superseded by the formation of tetraols which are derived from the anti-diol epoxide of benzo[a]pyrene [anti-BPDE;(+/-)-anti-7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene]. PAH-o-quinones produced by DD can inactivate the enzyme. These PAH-o-quinones also vary in their reactivity towards cellular nucleophiles, their cytotoxicity and their genotoxicity. Non-bay region and methylated bay-region PAH-o-quinones generated by DD are the most reactive Michael acceptors, and are also the most cytotoxic in hepatoma cells. Cytotoxicity results from the 1e- redox-cycling of the PAH-o-quinone, concomittant production of superoxide anion and a subsequent alteration in redoxstate. PAH-o-quinones are also genotoxic thus [3H]-benzo[a]pyrene-7,8-dione readily forms deoxyguanosine-adducts with native calf-thymus DNA, i.e., to the same extent as anti-BPDE. The cytotoxic and genotoxic properties of PAH-o-quinones suggest that DD may initiate a hitherto unrecognized pathway of PAH activation.
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PMID:Dihydrodiol dehydrogenase and its role in polycyclic aromatic hydrocarbon metabolism. 822 64

The conformational peculiarities of DNA and histones of chromatins of different origin have been studied using circular dichroism (CD). The chromatins were isolated from pigeon brain, rat thymus and liver, ascitic hepatoma 22A, C3HA mouse liver, pigeon erythrocytes and sea urchin sperm. The functional peculiarities of the chromatins were found to correlate with their compactness and the nucleosomal DNA repeat length. Analysis of chromatin CD spectra made it possible to define the degree of DNA compactness in oligonucleosomes and the secondary structure of their linker histones of the H1 family. It was found that in low ionic strength solutions the structures of chromatosomes are formed in erythrocyte and thymus chromatins, but not in sea urchin sperm chromatin. The size of the compact part of the DNA in the nucleosomes of transcriptionally active chromatins of brain and ascitic hepatoma 22A are less than the length of the DNA of the core particles under identical conditions. The secondary structure of the H1 histone from sea urchin sperm chromatin, unlike other linker histones of the H1 family, contains an additional alpha-helical segment in the C-terminal part. Analysis of structural changes of the both chromatin components during condensation of their oligonucleosomal chains with an increase in the ionic strength has been carried out.
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PMID:[Features of structural organization of chromatin from various sources]. 826 3

Four monoclonal antibodies were raised against crude gap junction fractions of rat liver to clarify the distribution of gap junctions during animal development and to analyze gap junction expression in vivo and the polarity of hepatocytes in vitro. Among the monoclonal antibodies obtained, HAM8 antibody recognized the 27-kDa rat liver gap junction protein connexin 32. This antibody recognized gap junctions at the contiguous faces of hepatocytes, and the antigen was also observed in exocrine pancreas and salivary gland but not in kidney, heart, esophagus, or thymus. HAM8 did not react with amphibian or fish liver, heart, esophagus, stomach, or intestine as assessed via the immunofluorescence method on frozen sections. A few hepatocytes and many hemopoietic cells were seen in rat fetal liver at 15 days of gestation. HAM8 antigen was expressed on some hepatocytes but not on any hemopoietic cells. As the fetus grew, the number of hepatocytes in the liver increased gradually, together with the amount of HAM8 antigen. The distribution of HAM8 antigen at 25 days after birth was similar to that in adult liver. When the expression of HAM8 antigen was examined in primary cultured hepatocytes using the immunofluorescence method, the antigen was observed clearly between the hepatocytes. However, most of the HAM8 antigen on the free surface of hepatocytes disappeared within 4 hr. HAM8 antigen was not expressed on AH-7974 rat hepatoma cells when they formed small islets in the rat peritoneal cavity or within the liver. When HAM8 IgG antibody was injected intravenously, the HAM8 signal was expressed in the liver.
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PMID:Immunohistochemical analysis of rat liver using a monoclonal antibody (HAM8) against gap junction. 838 23

Hepatomas tend to have a decreased glucose-6-phosphatase activity. We have observed phenotypic stability for this change in Morris hepatomas transplanted in rats. To determine if this decrease is selective for translocase functions or the hydrolase activity associated with glucose-6-phosphatase, we have compared activities in liver and hepatomas with glucose-6-phosphate or mannose-6-phosphate as substrates and with intact or histone-disrupted microsomes. In five out of seven subcutaneously transplanted rat hepatoma lines, the microsomal mannose-6-phosphatase activity was lower than in preparations from liver of normal or tumor-bearing rats. With liver microsomes and with most hepatoma microsomes, preincubation with calf thymus histones caused a greater increase in mannose-6-phosphatase than in glucose-6-phosphatase activity. In studies with liver and hepatoma microsomes there were similar increases in mannose-6-phosphatase activity with total calf thymus histones and arginine-rich histones. A smaller increase was seen with lysine-rich histones. The effect of polylysine was similar to the action of lysine-rich histones. There was only a small effect with protamine at the same concentration (1 mg/ml). Rat liver or hepatoma H1 histones gave only about half the activation seen with core nucleosomal histones. Our data suggested that microsomes of rat hepatomas tend to have decreased translocase and hydrolase functions of glucose-6-phosphatase relative to activities in untransformed liver.
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PMID:Changes in the glucose-6-phosphatase complex in hepatomas. 839 4

A human blood group B-active glycosphingolipid, belonging to the ganglio-series, was isolated from rat glioma cell line RG2 subcutaneous isografts. The oligosaccharide structure of the glycosphingolipid was completely characterized as Gal alpha 1-3(Fuc alpha 1-2)Gal beta 1-3GalNAc beta 1-4Gal beta 1-4Glc beta 1- 1'ceramide by NMR spectrometry, negative fast atom bombardment-mass spectrometry, sequential degradation by glycosidases and methylation analysis. Human blood group B antigenicity and the activity of this glycosphingolipid were confirmed by immunostaining on thin-layer chromatography and the inhibition of hemagglutination, respectively. Although the lipid has been detected in rat granuloma, bone marrow cells, spleen, thymus, ascites hepatoma cells and gastric mucosa, this is the first report of the occurrence of the B-active lipid in glioma.
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PMID:Human blood group B-active ganglio-glycosphingolipid in rat glioma. 839 23

The aim of this study was to survey the expression of an embryonic cytokine gene, MK, in the normal organs and neoplastic tissues of adults. Northern analysis showed that MK mRNA was exclusively expressed in the kidney among murine organs including thymus, lung, heart, spleen, liver, and kidney. In situ hybridization analysis revealed that MK expression was localized in the proximal tubules and metaplastic Bowman's epithelium, but not in other nephron segments such as glomeruli, loop of Henle, distal tubules, and collecting ducts. To investigate whether MK expression is a marker of tubular cell lineage, several cell lines originating from renal tubules were tested. No expression of MK was detected in PtK1 and LLC-PK1 cells derived from marsupial and porcine proximal tubules or in MDBK and MDCK cells from bovine and canine distal/collecting tubules. Unexpectedly, the MK gene was expressed in a human renal cell carcinoma line, VMRC-RCW, and the expression was up-regulated in the presence of retinoic acid. To elucidate the involvement of MK in the development of tumors, we further examined its expression in a variety of human neoplastic cell lines: YMB-1-C (breast cancer), EBC-1 (lung squamous cell carcinoma), RERF-LC-OK (lung adenocarcinoma), SBC-3 (lung small cell carcinoma), HSC-2 (mouth squamous cell carcinoma), NUGC-2 (gastric cancer), COLO201 (colon cancer), HepG2 (hepatoma), MIA PaCa-2 (pancreatic cancer), MCAS (ovarian cancer), HeLa (cervical cancer), BeWo (chorionic carcinoma), ITO-II (testicular tumor), T24 (urinary bladder tumor), and G-401 (Wilms' tumor). Strong signals were detected in COLO201, HepG2, ITO-II, T24, G-401, and weaker but distinct signals were detected in YMB-1-C, HSC-2, and MCAS cells. The MK gene was, therefore, widely expressed in neoplastic cells originating from genital organs, intestinal tract, liver, mammary gland, and urinary tract, and the expression was not restricted to adenocarcinomas, but was also observed in other types of tumor cells. These findings suggest that a retinoic acid responsive gene, MK, may play a role in the pathophysiology of renal proximal tubules and tumorigenesis in many types of neoplasms.
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PMID:A retinoid responsive cytokine gene, MK, is preferentially expressed in the proximal tubules of the kidney and human tumor cell lines. 843 39

To further define the hierarchy of human hematopoietic progenitor cells, we have attempted to identify antibodies to cell-surface molecules expressed on CD34+ progenitor cell subsets. Herein we describe the utility of a new monoclonal antibody, HCC-1, which binds to a novel epitope of CD59 differentially expressed among CD34+ progenitor cells. HCC-1 subdivides the adult marrow CD34+ population into HCC-1high and HCC-1low/- fractions of approximately equal size. Cobblestone area-forming cells (CAFC) in long-term bone marrow culture were enriched 10-30-fold in CD34+HCC-1high cells compared with CD34+HCC1-low/- cells and two-fold compared with CD34+ cells. When injected into fetal human bone fragments implanted in SCID mice, the CD34+HCC-1high population showed potent engrafting activity leading to the production of myeloid, lymphoid, and erythroid elements, as well as the retention of progenitor cell phenotype. These studies demonstrate that the CD34+HCC-1high population contains primitive pluripotent hematopoietic stem cells. No hematopoietic engrafting activity was detected in the CD34+HCC-1low/- population. Consistent with this finding, simultaneous five-color flow cytometric analysis revealed that HCC-1high cells include virtually all CD34+Thy-1+Lin- cells, a cell population previously characterized as highly enriched for primitive pluripotent hematopoietic stem cells. The ability of CD34+ cells divided into subsets by HCC-1 to produce T cells was assessed by transplantation of sorted cells into human fetal thymus implanted into SCID mice. A higher frequency of thymus-engrafting activity was observed in the CD34+HCC-1high than in the CD34+HCC-1low/- population. Consistent with the limited ability to engraft in the SCID-hu thymus model, the CD34+HCC-1low/- population was shown to contain a low frequency of CD34+CD10+ lymphoid progenitor cells. We conclude that the HCC-1 epitope is expressed at high levels on a subset of CD34+ cells that contain virtually all primitive pluripotent hematopoietic stem cells and that the population of CD59 molecules expressed on CD34+ cells is not homogeneous.
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PMID:High-level expression of a novel epitope of CD59 identifies a subset of CD34+ bone marrow cells highly enriched for pluripotent stem cells. 869 53

Highly reactive oxyradicals can be generated in vitro by iron-catalyzed aerobic oxidation of synthetic and naturally occurring substances capable of enolization in aqueous medium. Of biological interest are alpha-hydroxy- and alpha-aminocarbonyls such as carbohydrates, 5-aminolevulinic acid, and aminoacetone which tautomerize to the corresponding enediols and enolamines and yield oxyradicals initiated by electron transfer to dioxygen. Free radicals have been implicated in several normal and pathological processes. We briefly review our hypothesis of an in vivo prooxidant role of 5-aminolevulinic acid (ALA), the heme precursor accumulated in several porphyric disorders (e.g., lead poisoning, acute intermittent porphyria (AIP), tyrosinosis). Accordingly, i) ALA undergoes transition metal-catalyzed oxidation to give O-2, H2O2 and HO.; ii) ALA induces iron release from ferritin, lipid peroxidation of cardiolipin-rich vesicles, single strand breaks in plasmid DNA, and guanosine oxidation in calf thymus DNA; iii) ALA causes Ca(2+)-mediated rat liver mitochondria permeabilization; iv) rats chronically treated with ALA exhibit increased glycolytic metabolism; v) brain extracts of ALA-treated rats reveal increased levels of thiobarbituric acid reactive substances, direct chemiluminescence intensity, carbonyl proteins, ferritin, and "free iron" and gamma-aminobutyric acid-receptor dissociation constant, and vi) patients with AIP and lead-exposed workers present augmented erythrocytic levels of the antioxidant enzymes superoxide dismutase and glutathione peroxidase. These data indicate the involvement of ALA-generated reactive species in the clinical manifestations (neuropathy, mental changes, muscle weakness, hepatoma) shared by the aforementioned inherited and acquired porphyric diseases.
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PMID:Oxidative stress in acute intermittent porphyria and lead poisoning may be triggered by 5-aminolevulinic acid. 907 Mar 73

Rat AgB transplantation antigens were isolated after papain digestion of spleens from the inbred strain Hooded Lister. Both subunits of the AgB antigens were present in the purified material. Some physical characteristics of the antigens have been determined. An antiserum, raised in a rabbit, against the purified material reacted exclusively with AgB antigens on splenocytes but detected novel structures on both adult and embryonic fibroblasts. These structures, antigenically related to AgB antigens, were not detected on plasmacytoma or hepatoma cells, nor did they display any antigenic similarity with rat beta 2-microglobulin. Radioimmunoassays specific for the AgB antigen heavy chain and for beta 2-microglobulin, respectively, were used to estimate the contents of these antigens in several tissues. Spleen and thymus exhibit the largest density, while brain is almost devoid of these antigens.
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PMID:Properties of purified papain-solubilized rat AgB antigens and reactivity of a xenoantiserum against the isolated antigens. 953 30

There is currently little information concerning the time-dependent relationship between 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure and aryl hydrocarbon receptor (AHR) and aryl hydrocarbon receptor nuclear translocator (ARNT) protein concentration in vivo. Therefore, female Sprague-Dawley rats were given a single oral dose of TCDD (10 micrograms/kg), and the AHR and ARNT protein concentrations in liver, spleen, thymus, and lung determined by Western blotting. In liver, the concentration of AHR protein was significantly reduced 8 and 24 h postdosing as compared to time-matched controls. In spleen and lung, the concentration of AHR protein was reduced 3, 8, 24, and 168 h posttreatment compared to time-matched controls but returned to control levels by 336 h. In thymus, reductions in AHR protein concentration were observed 8, 24, 168, and 336 h postdosing as compared to time-matched controls. Significant reductions in the concentration of ARNT protein were not observed in any of the TCDD-exposed tissues. Functional studies in cell culture showed that exposure of a mouse hepatoma cell line (Hepa-1c1c7) and a rat smooth muscle cell line (A-7) to TCDD (1 nM) for 12 days resulted in a 50% reduction in TCDD-inducible reporter gene expression following subsequent challenge by an additional dose of TCDD (1 nM). Collectively, these results show that (i) TCDD-mediated depletion of AHR occurs in vivo, (ii) AHR protein does not rapidly recover to pretreatment levels even though the tissue concentration of TCDD has fallen, and (iii) reduction in AHR protein concentration correlates with reduction in TCDD-mediated reporter gene expression in mammalian culture cells.
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PMID:Female Sprague-Dawley rats exposed to a single oral dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin exhibit sustained depletion of aryl hydrocarbon receptor protein in liver, spleen, thymus, and lung. 957 24


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