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)

The binding patterns of the lectin Ulex Europaeus-I (UEA-I) to pancreatic cells of Wistar rats from TNO, in azaserine-induced acinar cell lesions, was examined by peroxidase-conjugated UEA-I. In the normal rat, acinar cells showed this lectin binding to luminal and intracytoplasmic cell membranes. Four different types of acinar cell nodules could be distinguished in this rat treated with azaserine. Acinar cell lesions, types 1-3, showed stronger lectin binding than was seen in normal tissue, whereas in type 4 lesions acinar cells showed similar or weaker binding than did the normal cells. In type 1 lesions, UEA-I binding was restricted to the luminal and intracytoplasmic cell membranes. Strong basolateral cell membrane binding not seen in the normal and type 1 or type 4 lesions was characteristic for type 2 lesions. Type 3 lesions were considered as the intermediate between type 1 and type 2. Comparison of histocytologic and UEA-I binding patterns demonstrated that type 1 lesions correspond to 'acidophilic nodules', type 2 to 'well- to moderately differentiated carcinoma', type 3 to 'in situ carcinoma' and type 4 to 'basophilic nodules'. Based on this classification, all 'nodules within nodules' observed in the pancreases of azaserine-treated rats were of malignant types. The present study indicates that UEA-I binding is a useful marker to differentiate between the benign and malignant lesions induced in rat pancreas by azaserine.
Carcinogenesis 1988 Nov
PMID:Ulex Europaeus-I: a marker for differentiation of (pre)cancerous lesions induced in the rat pancreas by azaserine. 318 Mar 43

Ram seminal vesicle (RSV) microsomal preparations activate benzidine and other arylamines to mutagenic species in a modified Ames assay. We have examined the mechanism of this activation process in more detail. The mutagenic effect was neither arachidonic acid-dependent nor indomethacin inhibitable. The mutagenic species was stable for at least 30 min in experiments in which addition of bacteria was delayed. Acetylbenzidine was a much more potent mutagen than benzidine in this system. Substitution of the acetylase-deficient tester strain TA98/1,8-DNP6 for strain TA98 markedly reduced the mutagenicity of acetylbenzidine and completely eliminated the mutagenicity of benzidine. Benzidine analogues 3,3'-dimethoxybenzidine (o-dianisidine), o-tolidine and 3,3',-5,5'-tetramethylbenzidine were not mutagenic in the RSV activation system. RSV-dependent activation of all radiolabeled congeners examined resulted in covalent binding to calfthymus DNA. The rank order of binding was: 3,3'-dichlorobenzidine greater than benzidine greater than o-dianisidine greater than acetylbenzidine greater than tetramethylbenzidine. This binding required active enzyme and arachidonic acid or hydrogen peroxide. The reactive species was short-lived: delayed addition of DNA reduced the level of binding nearly to zero. Binding was inhibitable by indomethacin, but this inhibition was incomplete in the cases of dichlorobenzidine and acetylbenizidine. We conclude that the extracellular generation of peroxidase-catalyzed oxidation products does not explain the RSV microsome-dependent mutagenicity observed with these compounds.
Carcinogenesis 1988 Jan
PMID:Ram seminal vesicle microsome-catalyzed activation of benzidine and related compounds: dissociation of mutagenesis from peroxidase-catalyzed formation of DNA-reactive material. 333 47

Mice were given i.v. injections of various tumor cell lines and, beginning 24 h later exposed for 3 weeks to 70% oxygen. Hyperoxia reduced the number of lung colonies derived from MT-7 cells (originally a mammary carcinoma) and of the lung-tumor derived cell lines 498 and Line-1 early passage. Lung colonies derived from Line-1 late passage, lines M109, B16-F10 and Lewis lung carcinoma were oxygen resistant. Lung metastases following i.m. injection of MT-7 cells were oxygen-sensitive and metastases derived from B16-F10 cells or Lewis lung carcinoma were oxygen resistant. Pre-exposure of mice for 48 h to 100% oxygen enhanced colony formation for all cell lines examined whereas exposure to 100% oxygen after i.v. injection only curtailed the growth of the cell lines previously shown to be sensitive to 70% oxygen. There was no correlation between oxygen sensitivity or resistance and the levels of total glutathione or activities of superoxide dismutase (SOD), glutathione reductase or peroxidase or glucose 6-phosphate dehydrogenase in the cell lines. However, upon injection in mice a resistant cell line increased its anti-oxidant defense mechanisms while growing in vivo whereas a sensitive cell line failed to show such adaptation.
Carcinogenesis 1988 Mar
PMID:Effects of hyperoxia on growth of experimental lung metastasis. 334 81

Histological studies using paired immunofluorescence staining and peroxidase-anti-peroxidase staining were performed on sections of rat livers with an antiserum specific for the 2-acetylaminofluorene (AAF)-DNA adduct N-deoxyguanosin-(8-yl)-aminofluorene (dG-8-AF). This is the predominant adduct in rat liver DNA at 5 (80%) and 28 (100%) days of AAF feeding. Nuclear staining was observed in livers of male Fischer rats fed 0.02% AAF for these time periods, and was not present in livers of animals fed control diet or detected when specific antiserum, first absorbed with the immunogen adduct, was utilized. In addition, nuclear staining was unchanged after incubation with RNase and abolished after incubation with DNase. Adducts were not readily detectable when whole-liver adduct concentrations were less than an average of 10(5) adducts per cell (30-50 fmol/micrograms DNA). The overall pattern of adduct distribution in livers of AAF-fed animals was distinctly non-uniform. A predominance of nuclear staining was found in the periportal areas by both immunofluorescence and immunoperoxidase procedures. In contrast, staining was very weak in the centrilobular areas. When animals were fed AAF for 28 days and control diet subsequently for 7, 14, 21 or 28 days, the overall intensity of the immunohistochemical staining decreased with time on control diet. However, the pattern of localization remained the same as in livers of rats fed AAF for 28 days, with the predominance of adducts being in the periportal areas. In male rats fed 0.02% AAF for 8 weeks, foci positive for gamma-glutamyltranspeptidase (GGT) became apparent, and the nuclei in these areas showed no immunofluorescence, indicating the absence of detectable levels of the dG-8-AF adduct. Twenty adduct-negative areas in the median lobes of three rat livers were positive for GGT, which suggests that loss of ability to form adducts in these regions occurs concomitantly with early phenotypic changes.
Carcinogenesis 1986 Jan
PMID:Immunohistochemical localization of DNA adducts in rat liver tissue and phenotypically altered foci during oral administration of 2-acetylaminofluorene. 351 Jul 47

An affinity purified sheep IgG antibody to a 20 amino acid peptide from the carboxyterminal end of RasHa p21 was used to localize RasHa p21 on fixed tissue sections of Harvey sarcoma (HaSV) virus-infected mice by the avidin-biotin-peroxidase immunocytochemical technique. Control sera included immune sheep sera absorbed with the peptide, preimmune sheep sera and a goat polyclonal antibody to Rauscher leukemia virus p30. Neonatal BALB/c mice were injected with HaSV/Moloney leukemia virus (MoLV), MoLV alone or buffer. Short-term fixation in Bouin's fixative was found to be the most effective method for demonstrating p21 in fixed tissue sections. RasHa p21 was found in 5-80% of the induced sarcoma cells, depending on the tissue fixative and antibody dilution. The antigen was localized to the cell membrane and in the cytoplasm. Tumors induced by NIH 3T3 cells transformed with cellular Ha-ras oncogenes had less than 1% immunoreactive tumor cells. Splenic erythroblasts in HaSV-induced erythroblastosis contained membrane antigen as did some reticular cells in lymph nodes draining the sarcomas. Normal tissues of virus-inoculated mice, uninoculated controls or fetuses and selected naturally occurring or induced liver tumors of mice, chemically induced skin tumors of mice, N-nitrosomethylurea-induced mammary tumors of rats, and naturally occurring tumors of F344/NCr rats did not contain immunoreactive p21. Thus, with the use of affinity purified IgG sheep polyclonal antibody to a peptide in RasHa p21, we were able to demonstrate RasHa p21 in tumors and other cells. The degree of immunoreactivity was related to the expected level of p21 expression.
Carcinogenesis 1986 Apr
PMID:Immunocytochemical localization of RasHa p21 in normal and neoplastic cells in fixed tissue sections from Harvey sarcoma virus-infected mice. 351 33

The effects of magnesium carbonate (MgCarb) on carcinogenesis and natural killer (NK) cell modulation by nickel subsulfide (Ni3S2) were studied. Male Fischer F344/NCr rats, 50-90 g body wt, 20 rats per group, received single i.m. injections into both thigh muscles of 2.5 mg Ni3S2 alone or combined with different proportions of MgCarb; the Mg/Ni molar ratio ranged from 0.25 to 4.0. Control rats received i.m. injections of normal saline or magnesium acetate (MgAcet), or s.c. MgCarb at a site distant from Ni3S2. The animals were observed over 79 weeks for the development of tumors. The NK cell activity was determined over the first 3 weeks of the experiment in separate groups of rats treated as above, with the use of the 51Cr/YAC-1 release assay for blood and spleen cells and the peroxidase localization of Ox-8-immunoreactive lymphocytes at the injection site. I.m. administration of MgCarb mixed with Ni3S2 up to the Mg/Ni molar ratio of 1.0 inhibited the carcinogenicity of Ni3S2 in a dose-related manner; final incidence of sarcomas decreased from 100 to 55% and the appearance of first tumors was delayed from 25 to 39 weeks. Higher doses of MgCarb did not exert further effect. Distant s.c. injection of MgCarb or local i.m. application of MgAcet did not change the carcinogenic potency of i.m. Ni3S2. MgCarb or saline alone did not produce any tumors. I.m. Ni3S2 had no significant influence on the activity of NK cells in blood and spleen, while i.m. MgCarb alone did not affect the NK activity in blood but doubled it transiently in the spleen 24 h after injection. In the injected muscle, Ox-8-positive cells became abundant around MgCarb but could not be found close to Ni3S2. This inhibitory effect of Ni3S2 was partially reversed by MgCarb. Also, numerous multinucleated giant cells infiltrated the sites of injection of MgCarb alone and MgCarb + Ni3S2 but not Ni3S2 alone. The results indicate a dose-dependent and strictly local character of the inhibition by MgCarb of Ni3S2 carcinogenesis, as well as a possible involvement of NK and phagocytic cells in this inhibition.
Carcinogenesis 1987 Jul
PMID:Nickel--magnesium interactions in carcinogenesis: dose effects and involvement of natural killer cells. 359 18

The interaction of plasmid DNA and metabolites of benzidine produced by the action of horseradish peroxidase and hydrogen peroxide was investigated by a combination of agarose gel electrophoresis and autofluorography. Benzidine becomes irreversibly bound to the DNA to form a macromolecular structure that can no longer penetrate a 0.8% agarose gel. Other carcinogens such as o-dianisidine, o-tolidine and amino-fluorene also reacted in this way but N4-tetramethylbenzidine and the non-carcinogenic 3,5,3',5',tetramethylbenzidine did not.
Carcinogenesis 1986 Sep
PMID:Peroxidase catalyzed aggregation of plasmid pBR322 DNA by benzidine metabolites in vitro. 374 27

A cytoplasmic polypeptide with a molecular weight of 14,000 (p14) was previously found to be the principal covalent target protein of the carcinogen, N-2-fluorenylacetamide (2-acetylaminofluorene), early during carcinogenesis in rat liver. The level of immunodetected p14 was markedly increased specifically during all stages of mitosis of hepatocytes in normal and regenerating partially hepatectomized livers. In addition, the polypeptide appeared to be immunologically and behaviorally related to a polypeptide with a molecular weight of 17,500 that is tightly bound to nucleosomes of chromatin in hepatocytes. This report describes the actions of the two polypeptides during hepatocarcinogenesis induced by ingestion of 3'-methyl-4-dimethylaminoazobenzene or N-2-fluorenylacetamide. Both carcinogens acted similarly in bringing about characteristic responses of the two polypeptides, detected immunohistochemically with specific rabbit antiserum and peroxidase-antiperoxidase complex. Four types of discrete hepatocytic lesions were observed. The earliest and least aberrant were hyperplastic foci of proliferating hepatocytes, which generally displayed markedly higher levels of immunostained p14 in cytoplasm, compared to levels in normal diploid hepatocytes. Furthermore, the very high concentrations of p14 were continuously present during cell interphase, in contrast to those in normal and regenerating hepatocytes, in which the elevation is restricted to the period of mitosis. Later-arising lesions were acidophilic adenomas of hepatocytes, which were characterized by quiescent morphology, fairly uniform and bulky eosinophilic cytoplasm, high levels of glycogen, and small delicate nuclei. These cells usually displayed little cytoplasmic p14. Coexistent hepatocytic lesions, i.e., mixed basophilic adenomas, exhibited considerable morphological heterogeneity, often slightly basophilic cytoplasm, and variable immunostain of cytoplasmic p14 during interphase. The fourth lesions were hepatocellular carcinomas, which continuously demonstrated much higher than normal levels of cytoplasmic p14 during cell interphase. During mitosis in the four types of hepatocytic lesions, the levels of immunostained p14 were usually further elevated above those in interphase, regardless of whether they were already very high during interphase in hyperplasia and malignancy, or low in acidophilic adenomas. All four kinds of carcinogen-altered lesions usually displayed little of the detectable Mr 17,500 polypeptide in nuclei.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Elevated expression and cell cycle deregulation of a mitosis-associated target polypeptide of a carcinogen in hyperplastic and malignant rat hepatocytes. 379 Dec 7

Incubation of human leukocytes with the synthetic estrogen and known human carcinogen, diethylstilbestrol (DES), for 40 min caused extensive DNA strand breakage (clastogenesis), as measured by a fluorometric assay. The level of DNA clastogenesis was dose dependent above an apparent threshold of 10 microM. Clastogenesis was increased by addition of cysteamine, a reducing agent and hydroxyl radical scavenger, and was blocked by low concentrations of plasma. DES epoxide, a weakly estrogenic derivative, was about one-tenth as potent as a DNA clastogen. Unexpected and paradoxical findings were observed when cells were treated with DES in the presence of a hydrogen peroxide-generating system plus a peroxidase. At the subthreshold concentration of 10 microM DES, the oxidizing system increased DNA clastogenicity, yet at 30 microM DES the oxidizing system decreased clastogenicity. The addition of superoxide dismutase to the oxidizing system increased clastogenicity at both concentrations of DES. DNA damage was largely blocked by arsenite, N-ethylmaleimide, iodoacetamide and bromophenacyl bromide. These experiments provide further indication of the complex nature of reactions involving DES which can lead to DNA damage and which may be relevant to DES-induced carcinogenesis.
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PMID:DNA clastogenic activity of diethylstilbestrol. 387 97

Antibodies raised in rabbits against the bovine serum albumin conjugates of O6-ethylguanosine (O6-EtGuo) and N-(guanosin-8-yl)-N-acetyl-2-aminofluorene (Guo-8-AAF) have been used in a double peroxidase-antiperoxidase staining assay to visualize the localization of DNA-O6-ethyldeoxyguanosine (O6-EtdGuo) and some of the interaction products of N-acetyl-2-aminofluorene (AAF) with DNA guanine in liver sections of rats treated with diethylnitrosamine (DEN), ethylnitrosourea (ENU), or AAF respectively. O6-EtdGuo could be detected in nuclei of parenchymal cells after injection of DEN (12-50 mg/kg) or ENU (140 mg/kg). Clear time and dose dependencies were observed. The lowest dose of DEN which, at 5 h after injection, resulted in immunohistochemically detectable levels of O6-EtdGuo, was 12 mg/kg; 5 h after 6 mg/kg no consistent difference between treated and untreated rats could be observed. A striking heterogeneity in staining pattern was observed after DEN: centrilobular regions were stained much more than peripheral zones. At 7 days after a single DEN injection of 50 mg/kg small rims of significantly stained hepatocytes could still be observed around the central veins. No heterogeneity of staining pattern was observed 2 h after ENU. ENU, in contrast with DEN, also resulted in a significant staining of nonparenchymal cells. At 24 h after ENU no significant staining of hepatocytes could be detected, but positive staining was still present in bile duct cells, vascular endothelial cells and sinusoidal cells. The results indicate a detection level of approximately 5 mumol O6-EtdGuo/mol DNA-P, i.e., 5 X 10(4) O6-EtdGuo residues per diploid genome. Using the anti-Guo-8-AAF antiserum, positive results were obtained 6 days after a single AAF dose of 0.5-10 mg/kg, corresponding to a detection limit of less than or equal to 0.4 mumol dGuo-8-(A)AF/mol DNA-P. Staining was rather homogenously distributed over the liver lobules. Persistency of the AAF-DNA interaction products was investigated both after 10 and 2 mg/kg AAF. Increased nuclear staining could be observed up to 8 weeks after 10 mg/kg and 4 weeks after 2 mg/kg.
Carcinogenesis 1985 Feb
PMID:Immunohistochemical localization of O6-ethyldeoxyguanosine and deoxyguanosin-8-yl-(acetyl)aminofluorene in liver sections of rats treated with diethylnitrosamine, ethylnitrosourea or N-acetylaminofluorene. 388 58


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