Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04040 (Catalase)
 3,577 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hyperplastic nodular cirrhosis was induced in rats by long-term (6 month) i.p. administration of thioacetamide at doses of 2.66 mmol/kg body wt, three times per week. The survival rate of animals at the end of the treatment was 90%. To follow the temporal changes samples at 0, 7, 15, 30, 45, 60, 90, 150 and 180 days from rats during thioacetamide intoxication and from chronological controls were obtained. The cirrhogenic ability of this treatment was assessed on the basis of morphological changes: the development of macronodular cirrhosis and the appearance of fibrous septa of collagen through portal spaces. Parameters of liver injury and cholestasis were obtained by assaying the serum activities of isocitrate dehydrogenase and gamma-glutamyltransferase. Enzymes and metabolites related to glutathione redox systems, as well as other antioxidant enzymes, were tested. Catalase and glutathione peroxidase, the two enzymes involved in the elimination of peroxides, and glutathione reductase decreased significantly at the end of the 6 months of intoxication, while Cu-Zn and Mn superoxide dismutases increased progressively during the long-term thioacetamide treatment. Protein thiol levels profile showed a biphasic change increasing from the 7th day and were insensitive to the 30% depletion of intracellular glutathione (GSH). To study the relationship of the intracellular thiols on the mechanisms of cell proliferation and differentiation during the cirrhogenic process, DNA content was assayed by flow cytometry in isolated hepatocytes, and DNA ploidy and distribution between G0-G1, S and G2 + M phases were determined. Remarkable changes in relation to a sharp increase in diploid population from 7 to 180 days (24.5%-->85.5%), a pronounced decrease in polyploid populations (tetraploid+octoploid) in the same period (73.7%-->12.3%), and elevations in the populations in S phase (S1 + S2) were observed in thioacetamide-treated rats. The results obtained indicate that hepatocytes isolated from thioacetamide-treated rats showed a marked tendency to diploidy, an enhancement in DNA replication parallel to the hepatic content of protein sulphydryl groups and a significant decline in antioxidant enzyme activities. The increase in protein thiols was independent of GSH level and of the thiol redox state.
Carcinogenesis 1995 Jul
PMID:Relationship between antioxidant systems, intracellular thiols and DNA ploidy in liver of rats during experimental cirrhogenesis. 761 93

The extent of DNA damage and lipid peroxidation induced by kaempferol, a polyphenolic flavonoid with a molecular structure similar to quercetin, was studied under aerobic conditions in isolated rat-liver nuclei. Kaempferol induced significant (P < 0.05) concentration-dependent nuclear DNA degradation concurrent with lipid peroxidation; these effects were enhanced by iron(III) or copper(II). Catalase, superoxide dismutase (SOD), mannitol, and sodium azide did not show any inhibitory effect on the kaempferol-induced nuclear DNA damage in the presence of iron(III) or copper(II). On the other hand, all stimulated the kaempferol-induced DNA damage in the presence of iron(III); in the presence of copper(II) only SOD and mannitol showed statistically significant stimulatory effects. The kaempferol induced lipid peroxidation was significantly stimulated by catalase and sodium azide in the presence of iron(III). These results demonstrate the pro-oxidant properties of polyphenolic flavonoids, which are generally considered as antioxidants and anticarcinogens, suggesting their possible dual role in mutagenesis and carcinogenesis.
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PMID:Kaempferol-induced nuclear DNA damage and lipid peroxidation. 795 31

The characteristics of the hepatocarcinogenesis induced by dehydroepiandrosterone (DHEA) were compared with that induced by other peroxisome proliferators such as [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio]acetic acid (Wy-14,643) and di(2-ethylhexyl)phthalate (DEHP). Male F-344 rats were given a diet containing DHEA at 0.5 or 1%, Wy-14,643 at 0.1% and DEHP at 2% for up to 78 weeks. In rats fed 0.5 or 1% DHEA the incidence of neoplasias was 20% after 52 weeks. At 78 weeks all rats treated with 1% DHEA had numerous grossly visible nodules and the incidence of hepatic neoplasia was dose-dependent. The magnitude of hepatocellular tumorigenicity after DHEA treatment was less potent than that after Wy-14,643, but more than that after DEHP treatment. Peroxisomal beta-oxidation activity increased three- or six-fold after a 10 week course of 0.5 or 1% DHEA respectively and this was significantly lower than that induced in Wy-14,643- or DEHP-fed rats. From 52 to 78 weeks these activities increased 3-9 times over that in controls. In both the group of rats treated with Wy-14,643 and those treated with DEHP, peroxisomal beta-oxidation constantly increased 11- to 15-fold during the experiment. Catalase activity increased 1.3- to 1.5-fold for the first 10 weeks of DHEA treatment and then recovered to the control level. The activities of glutathione peroxidase and glutathione S-transferase decreased markedly after 30 weeks in DHEA-treated rats and the decreases were sustained for up to 78 weeks. The profile of changes in enzyme activities in the rats fed DHEA was not significantly different from that of those fed Wy-14,643 or DEHP. There were no increases in 8-hydroxydeoxyguanosine, oxidative DNA damage or lipid peroxide level in the liver in any of the treated rats at 10 or 30 weeks. Since these results showed that the characteristics of hepatocarcinogenesis caused by DHEA were basically similar to those caused by Wy-14,643 and DEHP, typical peroxisome proliferators, hepatocarcinogenesis induced by DHEA is probably due to the same mechanisms as that induced by general peroxisome proliferators.
Carcinogenesis 1994 Oct
PMID:Characteristics of the hepatocarcinogenesis caused by dehydroepiandrosterone, a peroxisome proliferator, in male F-344 rats. 795 56

The role of reactive oxygen metabolites in the toxic effects of asbestos on pleural mesothelial cells is not well defined. We exposed rat pleural mesothelial cells (RPMC) to chrysotile and crocidolite fibers (0-40 micrograms/cm2) in the presence or absence of catalase and superoxide dismutase (SOD). Cell injury was measured using the colorimetric 3-4 (5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and DNA damage was evaluated in terms of unscheduled DNA synthesis (UDS). Catalase (100 U/ml) and SOD (250 U/ml) protected RPMC against asbestos-induced cytotoxicity and DNA damage. However, the inactivated enzymes and bovine serum albumin also showed some protection, suggesting that the effect of antioxidant enzymes may be partly related to their protein nature. These results suggest that oxygen derivatives are partly involved in the toxic effects of asbestos on cultures of RPMC. The presence of extracellular proteins may also decrease asbestos-produced toxicity by reducing the degree of RPMC-fiber interaction.
Carcinogenesis 1994 Jun
PMID:Role of oxygen derivatives in the cytotoxicity and DNA damage produced by asbestos on rat pleural mesothelial cells in vitro. 802 Jan 63

The extent of DNA damage and lipid peroxidation induced by myricetin, a polyphenolic flavonoid, were studied in isolated rat liver nuclei under aerobic conditions. Myricetin induced significant (P < 0.05) concentration-dependent nuclear DNA degradation concurrent with lipid peroxidation; these effects were enhanced by iron (III) or copper (II). Catalase, superoxide dismutase (SOD), mannitol and sodium azide did not inhibit myricetin-induced nuclear DNA damage in the presence of iron (III) or copper (II). However, all of these antioxidants stimulated myricetin-induced DNA damage in the presence of copper (II). Lipid peroxidation induced by myricetin was significantly inhibited only by SOD in the presence of copper (II), whereas it was enhanced by catalase and sodium azide in the presence of iron (III). These results demonstrate the pro-oxidant properties of polyphenolic flavonoids, which are generally considered to be antioxidants and anticarcinogens, and suggest a dual role for these flavonoids in mutagenesis and carcinogenesis.
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PMID:Interactions of flavonoids, trace metals, and oxygen: nuclear DNA damage and lipid peroxidation induced by myricetin. 833 Mar 5

Fanconi's anemia (FA) cells are highly susceptible to both reactive oxygen species and mitomycin C (MMC), a DNA cross-linking agent. In this study we have determined the amounts of 8-hydroxydeoxyguanosine (8OHdG), typical of oxidative DNA damage, in Epstein-Barr virus transformed lymphoblasts from FA patients and normal controls by the use of HPLC combined with electrochemical detection. FA cells (HSC72 and 99 cells being assigned to FA complementation group A) formed 2-3 times more 8OHdG than control cells after incubation with 20 mM H2O2 at 37 degrees C for 30 min. FA cells also formed more 8-hydroxyguanosine, typical of oxidative RNA damage, than control cells. FA cells showed decreased activity to decompose H2O2. Although the activity in FA cells was only 20-30% less than control cells, the remaining, undecomposed H2O2 concentration was almost twice as much in FA cells as in control cells, and the remaining H2O2 concentration correlated well with the amounts of 8OHdG formation. The H2O2 decomposing activity was almost completely inhibited by sodium azide (NaN3) or aminotriazole, both catalase inhibitors. With these inhibitors the amounts of 8OHdG formation were much higher than in those cells without inhibitors, and were almost the same in control cells as in FA cells. Catalase activity in FA cell lysates was 70-80% of controls. MMC also increased 8OHdG formation in FA cells only at ED100 but not at ED50. These results indicate that FA cells, at least FA complementation group A cells, have increased susceptibility to oxidative DNA damage, and that this increased susceptibility is possibly due to decreased catalase activity. These results also suggest that catalase plays an important role in protecting DNA from oxidative damage. However, this increased susceptibility to oxidative DNA damage is considered not to be the major cause of the increased susceptibility to MMC.
Carcinogenesis 1993 Jun
PMID:Increased formation of 8-hydroxydeoxyguanosine, an oxidative DNA damage, in lymphoblasts from Fanconi's anemia patients due to possible catalase deficiency. 838 71

Benzene is a widely recognized human carcinogen. The mechanism of DNA damage induced by major benzene metabolites 1,4-benzoquinone (1,4-BQ) and hydroquinone (1,4-HQ) was investigated in relation to apoptosis and carcinogenesis. Pulsed-field gel electrophoresis showed that cellular DNA strand breakage was induced by benzene metabolites. Internucleosomal DNA fragmentation and morphological changes of apoptotic cells were observed at higher concentrations of benzene metabolites. Flow cytometry showed an increase of peroxides in cultured cells treated with benzene metabolites. 1,4-BQ induced these changes at a much lower concentration than 1,4-HQ. Damage to DNA fragments obtained from the c-Ha-ras-1 proto-oncogene was investigated by a DNA sequencing technique. 1,4-BQ + NADH and 1,4-HQ induced piperidine-labile sites frequently at thymine residues in the presence of Cu(II). Catalase and bathocuproine inhibited DNA damage, suggesting that H2O2 reacts with Cu(I) to produce active species causing DNA damage. Electron spin resonance studies showed that semiquinone radical was produced by NADH-mediated reduction of 1,4-BQ and autoxidation of 1,4-HQ, suggesting that benzene metabolites produce O2- and H2O2 via the formation of semiquinone radical. These results suggest that these benzene metabolites cause DNA damage through H2O2 generation in cells, preceding internucleosomal DNA fragmentation leading to apoptosis. The fates of the cells to apoptosis or mutation might be dependent on the intensity of DNA damage and the ability to repair DNA.
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PMID:Oxidative DNA damage and apoptosis induced by benzene metabolites. 891 53

Reaction of chromium(VI) with alpha-lipoic acid (reduced form, also called 1,2-dithiolane-3-pentanoic acid) generated Cr(V) and hydroxyl radical (*OH) as measured by electron spin resonance and ESR spin trapping. 5,5-Dimethyl-1-pyrroline was used as a spin trapping agent. Catalase inhibited the *OH generation and enhanced the Cr(V) formation. Superoxide dismutase had an opposite effect. H2O2 enhanced the *OH generation and decreased the Cr(V) formation in a dose-dependent manner. Metal chelators, EDTA, diethylenetriaminepentaacetic acid, deferoxamine, and 1, 10-phenanthroline inhibited *OH radical generation in the order of EDTA > 1,10-phenanthroline > DTPA > deferoxamine. Oxygen consumption measurements indicated that molecular oxygen was used to generate *OH radical in the mixture of Cr(VI) and alpha-lipoic acid. H2O2 and superoxide radical (O2-) were involved as reactive intermediates. The *OH radical was generated via Cr(V)-mediated Fenton-like reaction (Cr(V) + H2O2 --> Cr(VI) + OH- + *OH). HPLC measurements show that the *OH radical generated by this reaction is capable of generating 8-hydroxyl-2'-deoxyguanosine from 2-deoxyguanosine. Incubation of Cr(VI) with cultured Jurkat cells resulted in an activation of DNA binding activity of the nuclear factor (NF)-kappaB. Addition of alpha-lipoic acid enhanced the NF-kappaB activation, while the *OH radical scavenger, sodium formate, inhibited it, showing that alpha-lipoic acid enhanced Cr(VI)-induced NF-kappaB activation via free radical reactions. The results indicate that while alpha-lipoic acid is considered to be an antioxidant, it may be a cellular one-electron Cr(VI) reductant and could be involved in the mechanism of Cr(VI)-induced carcinogenesis.
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PMID:One-electron reduction of chromium(VI) by alpha-lipoic acid and related hydroxyl radical generation, dG hydroxylation and nuclear transcription factor-kappaB activation. 902 68

Current models of Cr(VI) carcinogenesis suggest an important role for Cr(IV) as an intermediate, toxic, carcinogenic species, but direct chemical evidence has been lacking. This is because Cr(IV) is a highly reactive oxidation state of Cr and few Cr(IV)-based compounds are known that can be used as a model compound containing a biological ligand. This study reports the isolation of such a stable Cr(IV) complex. The Cr(IV)-GSH complex has been synthesized through the reaction of Cr(VI) with GSH. Its electron paramagnetic resonance (EPR) spectrum exhibits g = 1.9629 and a peak-to-peak line width of 480 G in aqueous medium as well as in the powder form. Magnetic susceptibility measurements showed that the compound has a magnetic moment of 2.53 Bohr magneton per Cr, establishing that the Cr ion has two unpaired electrons, hence its identity as Cr(IV). The Cr(IV)-GSH complex is able to generate hydroxyl (.OH) radical in the presence of molecular oxygen in aqueous medium. Catalase inhibited the .OH radical generation while H2O2 enhanced it, indicating that the .OH radical was generated via a Fenton-like reaction, H2O2 being generated as an intermediate in the reduction of molecular oxygen. Metal ion chelators, deferoxamine and 1,10-phenanthroline, attenuated the generation of Cr(IV)-mediated .OH radical. In the case of deferoxamine, a deferoxamine-derived free radical was generated as shown by EPR measurements. The results imply that Cr(IV) may play an important role in the mechanism of Cr(VI)-induced carcinogenesis and Cr(IV)-GSH can be used as a model compound to study the role of Cr(IV) in this mechanism.
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PMID:Synthesis of Cr(IV)-GSH, its identification and its free hydroxyl radical generation: a model compound for Cr(VI) carcinogenicity. 919 34

To clarify the mechanism of carcinogenesis by hair dyes, we compared the extent of DNA damage induced by mutagenic m-phenylenediamine and 4-methoxy-m-phenylenediamine, using 32P-5'-end-labeled DNA fragments obtained from the human c-Ha-ras-1 protooncogene and the p53 tumor suppressor gene. Carcinogenic 4-methoxy-m-phenylenediamine caused DNA damage at thymine and cytosine residues in the presence of Cu(II). Catalase and bathocuproine, a Cu(I)-specific chelator, inhibited 4-methoxy-m-phenylenediamine-induced DNA damage, suggesting the involvement of H2O2 and Cu(I). Superoxide dismutase (SOD) enhanced the DNA damage. Formation of 8-hydroxy-2'-deoxyguanosine (8-OH-dG) was induced by 4-methoxy-m-phenylenediamine in the presence of Cu(II). UV-visible spectroscopic studies have shown that Cu(II) mediated autoxidation of 4-methoxy-m-phenylenediamine and SOD accelerated the autoxidation. On the other hand, non-carcinogenic m-phenylenediamine did not cause clear DNA damage and significant autoxidation even in the presence of Cu(II). These results suggest that carcinogenicity of m-phenylenediamines is associated with ability to cause oxidative DNA damage rather than bacterial mutagenicity.
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PMID:DNA damage induced by m-phenylenediamine and its derivative in the presence of copper ion. 980 51


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