Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This investigation sought to characterize biochemically the tumor-specific transplantation antigens (TSTA) expressed on the cell surface of a panel of chemically induced fibrosarcomas of C3H/HeJ mice. Results suggest a uniform antigenic framework upon which individual specificities are superimposed. The antigens expressed by the 3-methylcholanthrene-induced fibrosarcomas MCA-D, MCA-F, and MCA-2A fulfill the requirements of a TSTA; namely, immunization of syngeneic hosts with irradiated cells or soluble extracts engenders a tumor-specific immune response such that animals resist challenge with the same, but not another, tumor. Brief incubation of intact tumor cells in single-phase aqueous solutions of 2.5% (v/v) 1-butanol extracts an immunoprotective TSTA, but not alloantigenic activity, from MCA-F cells. This extraction protocol was extended to the two other MCA-induced neoplasms. The butanol-extracted TSTA from the three tumors displayed isoelectric pHs of 6.4 to 6.6 following preparative isoelectric focusing. The tumor-specific immunoprotective activity from all three tumors displayed an apparent molecular weight of 150,000 (150 kDa) during high-performance gel permeation chromatography. The chromatographic properties of the 150 kDa antigens were unaffected by reduction using dithiothreitol, but incubation in acetate buffer, pH 3.0, dissociated the 150 kDa complex into at least two components with molecular weights of 70 to 100 kDa and 20 to 40 kDa. Only the smaller component displayed TSTA activity. The presence of two major components in the 150-kDa antigen was confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. TSTA activity was sensitive to digestion with pronase, papain, chymotrypsin, and alpha-mannosidase, but resistant to DNase, RNase, neuraminidase, trypsin, endoglycosidase H, and a mixed-function glycosidase. In addition, the TSTA activity was unaffected by heating. These data demonstrate that MCA carcinogenesis results in the expression of immunologically unique epitopes on biochemically related glycoproteins and suggest a unified mechanism for the generation of TSTA polymorphism.
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PMID:Biochemical characterization of 1-butanol-extracted murine tumor-specific transplantation antigens. 240 45

In this paper we describe an immunological method for the visualization of (+/-)7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10- tetrahydrobenzo[a]pyrene (BPDE-I) adducts in DNA by electron microscopy (EM). The immunoglobulin fraction of rabbit antiserum specific for BPDE-I adducts was digested with papain, the Fab fragments were purified by affinity chromatography on protein A-Sepharose and cross-linked to ferritin. The reactivity of the Fab fragments coupled to ferritin was determined by using anti-ferritin antibodies to precipitate the complexes formed between ferritin-labeled Fab fragments and BPDE-I-modified DNA that had been uniformly labeled with [14C]thymidine. DNA from cells treated with BPDE-I in culture was reacted with ferritin-labeled Fab fragments, separated from unreacted Fab using a Sepharose CL-4B column, and examined by EM. An aliquot of the same DNA was used to determine the level of BPDE-I adduction using an enzyme-linked immunosorbent assay (ELISA). Close agreement was found between the levels of adduction determined by ELISA and EM. A good correlation was also found between the level of adduction measured by EM and scintillation spectrometry when DNA was modified with [3H]BPDE-I in vitro. The EM method presents the following advantages: (i) it avoids cross-linking of separate adducts by the same IgG molecule; and (ii) it requires only one antigen-antibody reaction and a single purification step, allowing analysis of very small amounts of DNA.
Carcinogenesis 1989 Jan
PMID:Ferritin-labeled rabbit Fab fragments for the single-step detection of benzo[a]pyrene-diol-epoxide adducts in DNA by electron microscopy. 249 69

Adult rat liver gamma-glutamyltransferase (GGT) has been poorly characterized because of its very low concentration in the tissue. In contrast with the kidney, the liver enzyme is inducible by some xenobiotics, and its relationship to hepatic ontogeny and carcinogenesis seems to be important. Liver GGT polypeptides were identified by immunoblot analysis in subcellular fractions (rough endoplasmic reticulum, smooth endoplasmic reticulum, Golgi membranes and plasma membranes). Rat liver GGT appeared as a series of polypeptides corresponding to different maturation steps. Polypeptides related to the heavy subunit of GGT were detected in rough endoplasmic reticulum at 49, 53 and 55 kDa, and in Golgi membranes at 55, 60 and 66 kDa. Two polypeptides related to the light subunit of GGT were also observed in Golgi membranes. In plasma membranes GGT was composed of 100 kDa, 66 kDa and 31 kDa polypeptides. The 66 kDa component could correspond to the heavy subunit of the rat liver enzyme, and if so has a molecular mass higher than that of the purified rat kidney form of GGT (papain-treated). These data suggest different peptide backbones for the heavy subunits of liver GGT and kidney GGT.
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PMID:Electrophoretic mobility of gamma-glutamyltransferase in rat liver subcellular fractions. Evidence for structure difference from the kidney enzyme. 257 20

Highly specific antibodies bound to carcinogen adducts in DNA modified with (+/-)7 beta,8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE I) were quantitated by electron microscopy (EM) visualization and these observations were compared with quantitation of adducts by enzyme-linked immunosorbent assay (ELISA). The antiserum, elicited in rabbits following inoculation with BPDE I-modified DNA, has been found to be highly specific in its recognition of BPDE I-deoxyguanosine moieties. Parallel DNA samples prepared for analysis by ELISA and EM quantitation were randomized, encoded, and analyzed to determine extents of carcinogen modification in double-blind studies. After levels of modification were determined by immunoassays, DNA samples were prepared for EM analysis by incubation with amounts of anti-BPdG-DNA serum in excess of that necessary for complete binding of antibody to antigenic sites. At equilibrium, samples were enzymatically digested with papain in order to cleave anti-BPdG-DNA IgG molecules into Fab fragments in situ. Following column exclusion chromatography, BPdG-DNA-Fab complexes were incubated with ferritin-labeled Fab' fragments of goat [anti-rabbit F(ab')2] IgG in amounts in excess of those necessary for complete binding. When DNA samples were modified to between 0 and 40 fmol adduct/micrograms DNA, excellent agreement was obtained between ELISA quantitation and visualization by EM of antibodies bound to adducts.
Carcinogenesis 1985 Feb
PMID:Quantitation by electron microscopy of the binding of highly specific antibodies to benzo[a]pyrene-DNA adducts. 391 1

Six large hepatic nodules obtained 46 to 74 weeks after a single dose of diethylnitrosamine (0.625 or 1.25 micrograms/gm) in infant C57BLxC3H F1 male mice were studied to elucidate the nature of intracytoplasmic inclusions in the hepatic cells of these nodules. By light microscopy, the nodules constituted a spectrum of lesions ranging from some which were well differentiated adenomas to others which were frank carcinomas. Round or oval eosinophilic intracytoplasmic inclusions were consistently seen in the well differentiated adenomatous lesions. Some of these inclusions were PAS positive and resisted diastase digestion while others were either negative or only weakly PAS positive. By electron microscopy, they were most commonly crystalline, contained a reticulated electron dense material and were located in the distended rough endoplasmic reticulum. On immunofluorescence the inclusions showed marked specific reactivity with antisera against human alpha-1-antitrypsin. The presence of alpha-1-antitrypsin in these inclusions was further supported by the resistance of these inclusions to digestion by trypsin or papain but not by the pepsin or pronase.
Carcinogenesis 1980 Jun
PMID:Alpha-1-antitrypsin in intracellular inclusions of diethylnitrosamine induced hepatomas of C57BLxC3H F1 mice. 626 19

Free radicals have been suggested to be widely implicated as the species responsible for harmful biological processes, such as aging, carcinogenesis and numerous other diseases. The mechanism of biological damage produced in such processes has been investigated in a wide variety of systems, including studies on proteins, enzymes, nucleic acids and carbohydrates. In the present study we selected an ascorbic acid-transition-metal ion (ASA-Cu(2+)) system in order to understand the mechanism of soluble and membrane-bound enzyme inactivation by generating free radicals. Papain, a thiol protease, was immobilized on an immobilized-metal-ion carrier and used as a model to examine the inactivation behaviour of membrane-bound enzymes. A comparison was made between the inactivation of soluble and immobilized papain by free radicals, and the potential of different radical scavengers to prevent the inactivation of enzyme was examined.
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PMID:Studies on the inactivation of soluble and immobilized papain by the ascorbic acid-Cu2+ system: a model to propose the effect of free radicals on membrane-bound enzymes in vivo. 1173 Apr 89

Extensive efforts are exerted looking for safe and effective chemotherapy for hepatocellular carcinoma (HCC). Specific and sensitive early biomarkers for HCC still in query. Present work to study proteolytic activity and lysosomal membrane integrity by hepatocarcinogen, trichloroacetic acid (TCA), in Wistar rats against aqueous olive leaf extract (AOLE).TCA showed neoplastic changes as oval- or irregular-shaped hepatocytes and transformed, vesiculated, and binucleated liver cells. The nuclei were pleomorphic and hyperchromatic. These changes were considerably reduced by AOLE. The results added, probably for the first time, that TCA-induced HCC through disruption of hepatocellular proteolytic enzymes as upregulation of papain, free cathepsin-D and nonsignificant destabilization of lysosomal membrane integrity, a prerequisite for cancer invasion and metastasis. AOLE introduced a promising therapeutic value in liver cancer, mostly through elevating lysosomal membrane integrity. The study substantiated four main points: (1) the usefulness of proteolysis and lysosomalmembrane integrity in early prediction of HCC. (2) TCA carcinogenesis is possibly mediated by lysosomal membrane destabilization, through cathepsin-D disruption, which could be reversed by AOLE administration. (3) A new strategy for management of HCC, using dietary olive leaf system may be a helpful phytotherapeutic trend. (4) A prospective study on serum proteolytic enzyme activity may introduce novel diagnostic tools.
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PMID:Hepatocyte Lysosomal Membrane Stabilization by Olive Leaves against Chemically Induced Hepatocellular Neoplasia in Rats. 2199 69