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)

Delta-Aminolevulinic acid (ALA) is a heme precursor accumulated in lead poisoning and acute intermittent porphyria. ALA-induced DNA damage in the presence of metal ions was investigated with a DNA sequencing technique and a high-performance liquid chromatograph equipped with an electrochemical detector. ALA caused damage to DNA fragments obtained from c-Ha-ras proto-oncogene in the presence of Cu(II), but only slightly in the presence of Fe(II). ALA + Cu(II) induced piperidine-labile sites at thymine residues, especially in the 5'-GTC-3' and 5'-CTG-3' sequences of double-stranded DNA. Catalase and bathocuproine inhibited DNA damage induced by ALA + Cu(II). Typical .OH scavengers did not inhibit DNA damage, suggesting that active species other than .OH play a more important role in DNA damage. 8-Hydroxy-2'-deoxyguanosine formation by ALA increased with ALA concentration in the presence of Cu(II). Electron spin resonance studies using alpha-(1-oxy-4-pyridyl)-N-tert-butylnitrone as spin trap showed that carbon-centered radicals were generated during Cu(II)-catalyzed autoxidation of ALA. The major pathway of ALA autoxidation consists for the formation of 4,5-dioxovaleric acid and NH(4)+. Formation of a pyrazine derivative through ALA autocondensation was also observed. Concomitantly, O2- and H2O2 were generated during the Cu(II)-catalyzed ALA autoxidation. These results indicate that H2O2 reacts with Cu(I) to form a crypto-OH radical, such as the Cu(I)-peroxide complex, causing DNA damage. The possible mechanism for metal-dependent DNA damage by ALA is discussed in relation to the carcinogenicity of lead compounds and the increased frequency of liver cancer in acute intermittent porphyria.
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PMID:Mechanism of oxidative DNA damage induced by delta-aminolevulinic acid in the presence of copper ion. 862 Apr 94

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

DNA damage by metabolites of a food additive, butylated hydroxytoluene (BHT), was investigated as a potential mechanism of carcinogenicity. The mechanism of DNA damage by 2,6-di-tert-butyl-p-benzoquinone (BHT-quinone), 2,6-di-tert-butyl-4-hydroperoxyl-4-methyl-2,5-cyclohexadienone (BHT-OOH), and 3,5-di-tert-butyl-4-hydroxybenzaldehyde (BHT-CHO) in the presence of metal ions was investigated by using 32P-labeled DNA fragments obtained from the c-Ha-ras-1 proto-oncogene and the p53 tumor suppressor gene. BHT-OOH caused DNA damage in the presence of Cu(II), whereas BHT-quinone and BHT-CHO did not. However, BHT-quinone did induce DNA damage in the presence of NADH and Cu(II). Bathocuproine inhibited Cu(II)-mediated DNA damage, indicating the participation of Cu(I) in the process. Catalase also inhibited DNA damage induced by BHT-quinone, but not that induced by BHT-OOH. The DNA cleavage pattern observed with BHT-quinone plus NADH was different from that seen with BHT-OOH. With BHT-quinone plus NADH, piperidine-labile sites could be generated at nucleotides other than adenine residue. BHT-OOH caused cleavage specifically at guanine residues. Pulsed field gel electrophoresis showed that BHT-OOH and BHT-quinone induced DNA strand breaks in cultured cells, whereas BHT-CHO did not. Both BHT-quinone and BHT-OOH induced internucleosomal DNA fragmentation, which is the characteristic of apoptosis. Furthermore, flow cytometry analysis revealed an increase of peroxides in cultured cells treated with BHT-OOH or BHT-quinone. These results suggest that BHT-OOH participates in oxidative DNA damage directly, whereas BHT-quinone causes DNA damage through H2O2 generation, which leads to internucleosomal DNA fragmentation.
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PMID:Oxidative DNA damage and apoptosis induced by metabolites of butylated hydroxytoluene. 974 74

Homocysteine is considered to be an important risk factor for cancer as well as cardiovascular diseases. To clarify whether homocysteine has potential carcinogenicity, we investigated formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), which is known to be correlated with the incidence of cancer, induced by homocysteine in human cultured cell lines. Homocysteine increased the amount of 8-oxodG in human leukemia cell line HL-60, whereas the amount of 8-oxodG in its hydrogen peroxide (H(2)O(2))-resistant clone HP100 was not increased. We investigated the mechanism for oxidative DNA damage by homocysteine using (32)P-labeled DNA fragments obtained from human tumor suppressor genes and a proto-oncogene. There were two mechanisms by which homocysteine caused DNA damage in the presence of Cu(II). A low concentration of homocysteine (20 microM) frequently induced piperidine-labile sites at thymine residues, whereas a high concentration of homocysteine (100 microM) resulted in damage principally to guanine residues. Catalase inhibited DNA damage by 20 microM homocysteine, indicating the participation of H(2)O(2), but was ineffective in preventing DNA damage by 100 microM homocysteine. Experiments using a singlet oxygen probe showed that 100 microM homocysteine enhanced chemiluminescence intensity in deuterium oxide more than that in H(2)O. These results indicated that the metal-dependent DNA damage through H(2)O(2) is likely to be a more relevant mechanism for homocysteine carcinogenicity.
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PMID:Oxidative damage to cellular and isolated DNA by homocysteine: implications for carcinogenesis. 1278 61