Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006826 (cancer)
 1,092,456 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Reducing agents and cysteine, cysteamine, glutathione, ascorbic acid and H2O2 with and without the addition of Cu2+ did not increase significantly the frequency of mutations in the Salmonella test at non-toxic concentrations but triggered a marked DNA repair synthesis and induced a relatively high frequency of chromosome aberrations in cultured mammalian cells. Both latter effects were reduced by the addition of catalase to solutions of the reducing agents plus Cu2+. To avoid 'False Negatives' in mutagenicity screening the use of several test subjects including mammalian cells seems to be required.
Cancer Lett 1978 Oct
PMID:The need for a mammalian test system for mutagens: action of some reducing agents. 35 61

Tryptophan-p-1 (trp-p-1) and p-2, which have high mutagenic and carcinogenic potential, are oxidized by catalase- and horseradish peroxidase (HRP)-H2O2 intermediates with optimum pH 5.9 (0.2 M-acetate) in catalase and pH 5.0 (0.2 M-acetate), 8.0 (0.01 M-phosphate) in HRP. The rate constants (k4) of the oxidation in the catalase at pH 5.9 (0.2 M-acetate) were 2965 M-1 x sec-1 for trp-p-1 and 576 M-1 x sec-1 for trp-p-2. In the case of HRP, 1894 M-1 x sec-1, (pH 5.0, 0.2 M-acetate) for trp-p-1 and 705 M-1 x sec-1 (pH 8.0, 0.001 M-phosphate) for trp-p-2 under each optimum condition. The oxidation products of trp-p-1 and p-2 by catalase or HRP lost completely their mutagenic potential in the mutation assay.
Cancer Biochem Biophys 1979
PMID:Oxidation of tryptophan-P-1 and P-2 by beef liver catalase-H2O2 intermediate: comparison with horseradish peroxidase. 39 46

Exposure of mouse cells in culture to fluorescent light has been shown to produce chromatid breaks and exchanges. Hydrogen peroxide formed in the cell during illumination has been implicated as the causative agent. The present results indicate that susceptibility to light-induced chromosome damage increases with time in culture and seems to be associated with or requisite for the spontaneous malignant transformation of mouse cells. All three cell lines followed during long-term culture that either became tumorigenic or showed cytological evidence of neoplastic transformation developed a concomitant increase in susceptibility. In three additional cell lines, susceptibility to light-induced chromatid damage was significantly increased in the spontaneously transformed malignant cells as compared with their nonneoplastic precursors. The increased susceptibility is not simply the result of long-term culture, since three other nonneoplastic cell lines after prolonged culture were significantly less susceptible than their malignant counterparts. Increased susceptibility to light-induced chromatid damage could result from impaired DNA repair or from the loss of defense mechanisms for destroying H2O2 or scavenging free radicals.
Cancer Res 1979 Mar
PMID:Increased susceptibility of mouse cells to fluorescent light-induced chromosome damage after long-term culture and malignant transformation. 42 81

Freshly prepared ascorbate inhibited mitosis and induced chromosome aberrations in cultured Chinese hamster ovary cells. Cu(II) and Mn(II) (10(-4) or 10(-5) M) enhanced both actions. Fe(II) and Fe(III) (10(-4) or 10(-5) M) reduced or abolished the mitosis-inhibiting action of ascorbate. At 10(-4) M, Fe(II) and Fe(III) strongly enhanced the chromosome-damaging capacity of ascorbate. Up to 100% of all examined metaphase plates had multiple chromosome exchanges or breaks. Since the cytostatic and clastogenic effect of ascorbate of H2O2 to induce chromosome aberrations was examined. H2O2 and a H2O2: Fe(II) mixture (Fenton reagent) induced chromosome breaks and exchanges but to a lesser degree than did ascorbate: Cu(II), Mn(II), Fe(II), or Fe(III) mixtures. Whether the strong chromosome damaging capacity of ascorbate plus transition metals as seen in the in vitro test system poses a health hazard only properly designed in vivo studies can reveal.
Cancer Res 1979 Oct
PMID:Enhancement of the chromosome-damaging action of ascorbate by transition metals. 47 51

(1) Oxygen uptake and lactate production of different strains of ascites tumor cells were assayed after exposure to an extracellular photochemical system known to produce reactive oxygen derivatives. The various cells tested showed differential sensitivity to the treatment, ranging from nearly full inactivation of Ehrlich cells to nearly full resistance of Yoshida cells. (2) Glucose plus succinate added after the treatment reestablished basal oxygen uptake capacity suggesting that the cell membrane was the primary site of damage. This was confirmed by dye-permeabilization and protein leakage in sensitive cells. (3) H2O2 was shown to be the only relevant oxygen derivative in the production of cell damage: catalase was the only externally added agent that protected sensitive cells, and H2O2 (congruent to 10(-3) M) had the same effects as the photochemical treatment. (4) While the absence of catalase is a feature common to all tumors tested, sensitivity to H2O2 appears to be related to cellular levels of glutathione peroxidase and of its subsidiary enzymes glucose-6-phosphate dehydrogenase, glutathione reductase and glutathione synthetase.
Cancer Biochem Biophys 1979
PMID:Differential sensitivity of tumor cells to externally generated hydrogen peroxide. Role of glutathione and related enzymes. 55 3

We have shown that N-hydroxy-2-acetylaminofluorene, a metabolite of 2-acetylaminofluorene, is converted via a nitroxide free radical into N-acetylaminofluorene and 2-nitrosofluorene by H2O2 in the presence of methemoglobin. Utilizing optical methods, we have demonstrated that the rate of 2-nitrosofluorene production parallels that of N-hydroxy-2-acetylaminofluorene oxidation. This evidence is consistent with a model whereby two molecules of N-hydroxy-2-acetylaminofluorene yield two nitroxide free radicals which then dismutate to form one molecule of N-acetoxy-2-acetylaminofluorene and one molecule of 2-nitrosofluorene. The Km of N-hydroxy-2-acetylaminofluorene for this reaction is 114 microM with a Vmax of 50 microM/min.
Cancer Biochem Biophys 1979
PMID:Free radical activation of N-hydroxy-2-acetylaminofluorene by methemoglobin and hydrogen peroxide. 55 9

Dietary 3-amino-1H-1,2,4-triazole (AT), although carcinogenic when administered alone, was an antitumor agent when combined with certain other carconogenic stimuli. The carcinogenic effect was prominent in the livers of C3H mice; thyroid tumors were less common because they required a longer period of development, and the life-span of the animal was shortened by the AT diet. The antitumor effects of AT included: delay in appearance of mammary tumors, striking reduction in gamma-radiation-induced lymphomas, and sharp reduction in neutron radiation-induced harderian gland and ovarian tumors. On an AT diet, the inbred C3H acatalasemic mouse substrain developed more liver tumors, starting earlier, than did the C3H normal catalase substrain. We suggest that our findings pointed to a possible relevance of catalase and H2O2 in carcinogenesis. The most probable mechanism for the increased incidence of liver tumors in AT-treated acatalasemic mice was the diminished rate of degradation of endogenous H2O2.
J Natl Cancer Inst 1978 May
PMID:Carcinogenic and antitumor effects of aminotriazole on acatalasemic and normal catalase mice. 64 30

Horseradish peroxidase and H2O2 mediate N-hydroxy-N-acetyl-2-aminofluorene (N-OH-AAF) conversion into two more potent carcinogens, 2-nitrosofluorene and N-acetoxy-N-acetyl-2-aminofluorene. Optical studies of this system indicate that horseradish peroxidase is operating as a peroxidase with N-OH-AAF as the electron donor. Our studies confirm the earlier finding that 2-nitrosofluorene and N-acetoxy-N-acetyl-2-aminofluorene are the products of the type II enzyme-mediated oxidation of N-OH-AAF, but surprisingly, the results with the type VI enzyme indicate that more 2-nitrosofluorene was formed and, in addition, another product absorbing at 245 nm was formed. If ascorbate is present in the N-OH-AAF/horseradish peroxidase/H2O2 system, ascorbate is oxidized preferentially. Cyanide, a known inhibitor of the peroxidase, does not inhibit when N-OH-AAF is the electron donor. The reaction products are the same in the presence or absence of cyanide.
Cancer Res 1976 Apr
PMID:Horseradish peroxidase/hydrogen peroxide-catalyzed oxidation of the carcinogen N-hydroxy-N-acetyl-2-aminofluorene as effected by cyanide and ascorbate. 126 Jul 68

Carcinogenic N-nitrosomethylaniline is oxidized in vitro by horseradish peroxidase in the presence of H2O2 to ultimate carcinogens, which bind to DNA and transfer RNA (tRNA). tRNA is more accessible for modification by the activated carcinogen studied. The modification of nucleic acid by N-nitrosomethylaniline metabolite(s) formed by peroxidase is inhibited by some compounds of physiological importance (ascorbate, glutathine) and by radical trapping agents (nitrosobenzene, methyl viologen). 32P-postlabeling assay of DNA and tRNA modified by N-nitrosomethylaniline activated by peroxidase shows covalent adduct formation with nucleic acids. The role of peroxidases in the activation of N-nitrosamines leading to organ and/or cell specificity of these carcinogens is discussed.
Cancer Lett 1992 Mar 31
PMID:Peroxidase oxidizes N-nitrosomethylaniline to ultimate carcinogens(s) binding to DNA and transfer RNA in vitro. 131 33

We have previously shown that RSV-SR-transformed hamster cells acquire high resistance to H2O2, i.e. the cytotoxic product of activated macrophages (H2O2R) and that they begin to secrete PGE (PGES), thus inactivating the CTA of NK cells. Among normal cells, the same phenotype is expressed in activated macrophages. In all our RSV-transformed cells these 2 properties were jointly expressed and correlated with high tumorigenicity and experimental metastasizing of these cells. We now show that transfection of 3 RSV-SR-transformed cell strains with activated N-ras leads either to complete inhibition of the H2O2R + PGES phenotype in all clones of one strain, or to inhibition of PGES only in the majority of clones of 2 other strains. Unexpectedly, the complete or partial inhibition of this phenotype did not alter the high tumorigenicity of 2 strains of these cells, but lower tumorigenicity was evident in almost all clones of the third strain (as well as in some gene-neo-transfected clones of these strains). The loss of PGES made these cells susceptible to the CTA of NK cells, while the loss of H2O2R did not alter their resistance to the CTA of macrophages. Expression of the H2O2R + PGES phenotype was retained in all cloned variants of control, gene-neo-transfected cells. The possible relation of the N-ras gene to regulation of src gene activities in RSV-SR-transformed cells is discussed.
Int J Cancer 1992 Jul 30
PMID:Clustering of discrete cell properties essential for tumorigenicity and metastasis. III. Dissociation of the properties in N-ras-transfected RSV-SR-transformed cells. 132 77


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