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 induced chemoluminescence in rat liver mitochondrial preparations was studied in the course of 2-acetylaminofluorene or N-nitrozodiethylamine induced hepatocarcinogenesis. As follows from the literature, the intensity of chemoluminescence is representative of catalase activity, i. e. of one of mitochondrial enzymes. Beginning from the stage of stimulation of pretumor cell proliferation, the course of carcinogenesis is caracterized by a progressive decrease in the intensity of chemoluminescence. An adrenomimetic noradrenaline induced a similar effect, whereas isoprenaline and alpha-adrenoblocator pirroxane stimulated chemoluminescence of mitochondria preparation in the intact rats. Ortobenzoquinone being oxidated with H2O2, noradrenaline and isoproteranol were deprived of oxidative activity. It is suggested that inhibition of mitochondrial catalase activity with endogeneous noradrenaline constitues a primary mechanism of the decrease in chemoluminescence intensity.
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PMID:[Primary mechanism of a reduction in the intensity of extremely weak mitochondrial luminescence in the process of chemical hepatic carcinogenesis]. 52 62

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.
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PMID:Carcinogenic and antitumor effects of aminotriazole on acatalasemic and normal catalase mice. 64 30

The factors-regulators of post-transcriptional regulation of the rate of catalase synthesis in the rat liver were studied under normal conditions and in carcinogenesis (the 2nd, 7th and the 14th days after the transplantation of Pliss lymphosarcoma). Factors Fact and Fing were purified from the supernatant and PH5-supernatant fractions of the rat liver by means of chromatography and rechromatography on DEAE-cellulose. A simple method of determination of the biological activity of these factors in vivo was proposed. Synthesis of catalase took place when (see article) (the 2nd and 14th days after the inosulation). The enzyme synthesis was absent when (see article) (7th day after the inoculation).
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PMID:[Factors of post-transcription regulation of the rate of liver catalase synthesis in tumor-bearing rats]. 98 27

Chromium(VI) and Cr(V) compounds increased the concentration of 8-hydroxydeoxyguanosine (oh8dG) in isolated DNA, whereas no such increase was seen with Cr(III). Furthermore, incubating DNA with H2O2 and Cr(VI) or Cr(V) potentiated the formation of oh8dG above levels observed with either chromium compound alone. In the presence of catalase, the increase in DNA oxidation observed with Cr(VI) was inhibited, the base oxidation observed being equivalent to background levels, and this indicated involvement of H2O2 in the mechanism. Glutathione did not enhance chromium-induced formation of this oxidized base. These results help to explain a mechanism of chromium-induced DNA oxidation involving H2O2 via a Fenton-type reaction.
Carcinogenesis 1992 Sep
PMID:Production of 8-hydroxydeoxyguanosine in isolated DNA by chromium(VI) and chromium(V). 132 73

Forty-eight human squamous cell lung carcinomas of previously untreated patients were analyzed for resistance to doxorubicin and for the presence of topoisomerase II (Topo II), metallothionein (MT), thymidylate synthase (TS) and catalase (Cat). Significant correlations exist between resistance to doxorubicin measured by the in vitro short-term test and overexpression of MT and TS measured by immunohistochemistry. No significant correlation was found between resistance and expression of Topo II or Cat. No significant interrelationship between smoking habits of patients and expression of Topo II, MT, TS or Cat was found.
Carcinogenesis 1992 Nov
PMID:Expression of topoisomerase II, catalase, metallothionein and thymidylate-synthase in human squamous cell lung carcinomas and their correlation with doxorubicin resistance and with patients' smoking habits. 133 Mar 47

Pulsed field gel electrophoresis showed that caffeic acid induced DNA strand breaks in cultured human cells in the presence of Mn(II). With alkali treatment, DNA single-strand breaks were observed. The strand breakage was increased by the treatment of buthionine sulphoximine (a GSH synthesis inhibitor) and 3-aminotriazol (a catalase inhibitor) and decreased by catalase, indicating the involvement of H2O2. The DNA damage was decreased by o-phenanthroline, indicating the involvement of transition metal ion. Damage to isolated DNA from c-Ha-ras-1 protooncogene was investigated by a DNA sequencing technique. Caffeic acid caused DNA damage in the presence of Cu(II) but not in the presence of either Mn(II) or Fe(III). Caffeic acid plus Cu(II) induced piperidine-labile sites frequently at thymine residues, especially of the 5'-GTC-3' and 5'-CTG-3' sequences. Typical OH scavengers showed no inhibitory effects. The inhibitory effects of bathocuproine and catalase on Cu(II)-mediated DNA damage suggest that Cu(I) and H2O2 have important roles in the production of active species causing DNA damage. The Cu(II)-mediated DNA damage was enhanced by pre-incubation of caffeic acid with Mn(II). Mn(II)- or Cu(II)-catalyzed autoxidation of caffeic acid produced H2O2 with efficiency of Mn(II) greater than Cu(II). These results suggest that in the presence of Mn(II) or Cu(II), caffeic acid produces H2O2, which is activated by transition metals to cause damage to DNA in vitro and probably in cultured cells.
Carcinogenesis 1992 Sep
PMID:Caffeic acid causes metal-dependent damage to cellular and isolated DNA through H2O2 formation. 139 30

Oxidative DNA damage is involved in mutagenesis, carcinogenesis, aging, radiation effects, and the action of several anticancer drugs. Accumulated evidence indicates that iron may play an important role in those processes. We studied the in vitro effect of low concentrations of Fe(II) alone or Fe(III) in the presence of reducing agents on supercoiled plasmid DNA. The assay, based on the relaxation and linearization of supercoiled DNA, is simple yet sensitive and quantitative. Iron mediated the production of single and double strand breaks in supercoiled DNA. Iron chelators, free radical scavengers, and enzymes of the oxygen reduction pathways modulated the DNA damage. Fe(III)-nitrilotriacetate (NTA) plus either H2O2, L-ascorbate, or L-cysteine produced single and double strand breaks as a function of reductant concentration. A combination of 0.1 microM Fe(III)-NTA and 100 microM L-ascorbate induced detectable DNA strand breaks after 30 min at 24 degrees C. Whereas superoxide dismutase was inhibitory only in systems containing H2O2 as reductant, catalase inhibited DNA breakage in all the iron-mediated systems studied. The effect of scavengers and enzymes indicates that H2O2 and .OH are involved in the DNA damaging process. These reactions may account for the toxicity and carcinogenicity associated with iron overload.
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PMID:Iron-mediated DNA damage: sensitive detection of DNA strand breakage catalyzed by iron. 143 83

Caloric restriction increases maximum achievable lifespan and offsets the time to development of degenerative disease. Part of these desirable effects may result from positive modulation of toxic events. We have shown that when rodents are placed on a diet that is reduced in total calories by 40%, several beneficial changes on biochemical systems which impact on toxicologic processes are positively enhanced. Lipid metabolism is reduced and, therefore, the potential for lipoperoxidation is reduced. Additionally, activity of enzymes that produce free radicals as byproducts (cytochrome P4502C11) are also reduced. Concurrently, we have shown that the "effective" activity of catalase and the activity of superoxide dismutase (which are required for the detoxification of toxic oxygen radicals) are significantly increased by caloric restriction. The activities of enzymes of drug and xenobiotic metabolism are also altered by caloric restriction. The effect upon activity may be to either decrease or increase activity, dependent upon whether the enzyme activates compounds to intermediates which may be more toxic or whether the enzyme acts to reduce toxicity. We have also shown that caloric restriction may affect the initiation stage of carcinogenesis. Aflatoxin B1 binding to hepatic nuclear DNA was reduced by caloric restriction (caloric restriction reduced both major adducts that are formed upon exposure to aflatoxin B1). caloric restriction also reduced cytochrome P4502C11 which converts aflatoxin B1 to its toxic epoxide, and may partly explain the reduction in binding. These results suggest that caloric restriction may, in part, extend the time to development of degenerative disease by altering basic biochemical mechanisms of toxicity.
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PMID:Modulation of chemical toxicity by modification of caloric intake. 144 3

Treatment of rats with a single carcinogenic dose of CdCl2 (i.e., 30 mumol/kg) caused severe hemorrhagic damage in the testis within the first 12 h after the metal. Subsequently, atrophy with calcification developed in the next 2-3 mo. Atrophied tissues regenerated during the 1 yr after exposure. Twelve hours after exposure to the Cd treatment, lipid peroxidation levels, Fe content, and cellular production of H2O2 were remarkably elevated in testicular Leydig cells, the target cell population for Cd carcinogenesis. At the same time, glutathione peroxidase activity rose, glutathione reductase and catalase activities were reduced, and superoxide dismutase activity was unchanged. Xanthine oxidase activity in Leydig cells was also elevated at 6 and 9 h after the Cd treatment. Reduced glutathione in testes was decreased and oxidized glutathione was increased 12 h after exposure to the metal. These facts suggest that the carcinogenic doses of Cd induced oxidative stress while compromising cellular defense mechanisms against such stress. Therefore, active oxygen species such as H2O2 may have an important role in the initiation of carcinogenesis within the target cell population.
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PMID:Role of oxidative stress in single-dose, cadmium-induced testicular cancer. 152 11

Increases in acyl coenzyme A (CoA) oxidase activity due to peroxisome proliferation are postulated to cause oxidative stress via elevated production of H2O2, leading to DNA damage. These changes are suspected to be responsible for tumor formation caused by non-genotoxic carcinogens which do not bind to DNA but cause proliferation of peroxisomes. However, the activity of the peroxisomal enzyme acyl CoA oxidase assayed in vitro in the presence of excess fatty acyl CoA substrate may not reflect rates of H2O2 generation in intact liver where fatty acid supply is carefully controlled in part by delivery of substrate. The purpose of this work was to determine if rates of hepatic H2O2 generation were altered in perfused liver and in vivo following induction of H2O2-generating acyl CoA oxidase activity. Injection of the potent peroxisome proliferating agent perfluorooctanoate into rats 5 days prior to sacrifice caused an expected 4-fold increase of H2O2-generating acyl CoA oxidase activity measured in hepatic homogenates. In contrast, rates of H2O2 generation in perfused liver measured spectrophotometrically (660-640 nm) through a lobe of the liver were not altered by perfluorooctanoate treatment (7.3 +/- 1.5 vs. 7.8 +/- 0.5 mumol/g/h in livers from untreated control rats). Similar treatment with perfluorooctanoate also increased in vitro acyl CoA oxidase activity 9-fold in livers from deermice; however, rates of elimination of methanol, a selective substrate for catalase in rodents whose oxidation is limited by the supply of H2O2, were not altered significantly in vivo (control, 110 +/- 11 mumol/g/h vs. perfluorooctanoate, 112 +/- 32 mumol/g/h). Taken together, these data demonstrate that elevation of H2O2 formation by acyl CoA oxidase activity measured in vitro is not necessarily associated with increases in rates of H2O2 generation in intact perfused liver or in vivo, most likely due to rate-limitation in intact cells by fatty acid supply. These data do not support the hypothesis that the induction of peroxisomes leads to excessive H2O2 production and oxidative stress. It follows that alternative hypotheses to explain carcinogenesis caused by peroxisome-proliferating agents need to be considered.
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PMID:Induction of peroxisomes by treatment with perfluorooctanoate does not increase rates of H2O2 production in intact liver. 153 82


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