Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.11.1.7 (peroxidase)
 65,474 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Contribution of various hemoproteins to peroxidase oxidation of benzidine and its derivatives as well as effects of these substances on functional state of hepatocytes are discussed. Benzidine and its derivatives were shown to induce those forms of cytochrome P-450 which were involved in accelerated oxidation of the carcinogenic drugs studied as well as affected the glutathione transferase, NADPH-dependent glutathione reductase activities and the activity of antioxidant system enzymes. Increase in content of cytochrome P-450, glutathione-dependent enzymes and other effects specific for adult hepatocytes, which occurred in presence of aminobiphenyls, were accompanied by decrease in content of receptors to epidermal factor of growth regulating the hepatocytes proliferation.
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PMID:[The role of carcinogenic aminobiphenyls in hepatocyte differentiation]. 181 15

Authors have studied the application of benzidine and its derivatives for the demonstration of the marker enzyme horseradish peroxidase. Benzidine compounds are known to be in a blueish dimeric form under oxidative circumstances, while after polymerization they yield a dark brown end product. If the dimeric state is stabilized, the 3,3'-dimethoxy benzidine (o-dianisidin) appears to be the most suitable to demonstrate peroxidase. The o-dianisidin reaction has the advantage of high sensitivity and that the end product shows a birefringence in polarized light. Upon mounting with organic media the end product is stable.
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PMID:[Benzidine and its derivatives in the immunohistochemical analysis of peroxidase]. 250 6

Benzidine and several derivatives are activated to mutagenic species in an H2O2-dependent Ames test system. Optical and electron paramagnetic resonance (EPR) spectroscopy are employed in studies of the H2O2-dependent oxidation of benzidine and 3,5,3',5'-tetramethylbenzidine (TMB) catalyzed by intact bacteria, and provide direct evidence for peroxidase activity in Salmonella typhimurium. The acetylase-proficient Ames tester strain TA98 and its acetylase-deficient derivative TA98/1,8-DNP6 are equally responsive to H2O2-dependent mutagenicity; enzymatic acetylation appears not to be involved in activation of benzidine, in this system. The H2O2-dependent mutagenicity of benzidine and oxidation of TMB are observed when the assays are carried out in acetate buffer (pH 5.5), but not in 2-[N-morpholino]ethane sulfonic acid (MES) buffer, at the same pH. This difference is interpreted in terms of the effects of these buffers on the intracellular pH of the bacteria. The H2O2-dependent mutagenicity of several benzidine congeners is also described.
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PMID:Peroxidative metabolism of benzidine derivatives by Salmonella typhimurium. 282 24

Benzidine oxidative activation may proceed by peroxidase-catalyzed one-electron oxidation via free radical intermediates, or by N-acetylation followed by monooxygenase-catalyzed N-hydroxylation. The peroxidase route has been examined by using horseradish peroxidase or prostaglandin H synthase in vitro. In the presence of nucleophiles such as phenols, thiols, or nucleic acids, isolable adducts are formed. The structures of these adducts have been elucidated by spectroscopic methods. The Ames test provides a useful system for studying benzidine bioactivation to mutagenic intermediates. An endogenous bacterial acetylase plays an important auxiliary role in the hepatic S9-dependent activation of benzidine. Bacterial peroxidases may also support benzidine oxidation in the Ames test.
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PMID:Benzidine: mechanisms of oxidative activation and mutagenesis. 309 4

The ability of eight different aromatic amines to serve as reducing substrates for the conversion of 5-phenyl-4-pentenyl-hydroperoxide to 5-phenyl-4-pentenylalcohol by prostaglandin H synthase (PHS) was studied. The methodology used a direct assay for the reduction of hydroperoxide to alcohol and allowed an assessment of the reducing substrates' efficiency as a donor of electrons to the peroxidase component of highly purified PHS. The eight amines tested include, 1-naphthylamine, 2-naphthylamine, 2,4-diaminoanisole, 2,5-diaminoanisole, 2-aminofluorene, 2-acetylaminofluorene, 2-amino-anthracene and benzidine. The compounds tested were either very efficient substrates or showed minimal activity as reducing substrates. Benzidine, 2,4-diaminoanisole and 2,5-diaminoanisole were excellent substrates providing nearly stoichiometric hydroperoxide reduction even at low enzyme concentrations. On the other hand, the five remaining compounds showed no activity as reducing substrates. Increases in enzyme and/or substrate concentration still did not produce any significant enzymatic activity with the poor substrates. The results of these investigations provide important information concerning the metabolic activation of these aromatic amines by PHS. There is evidence in the literature that some of these amines are metabolized by PHS to mutagenic and carcinogenic species. For the efficient reducing substrates this remains a reasonable suggestion. However, for the poor reducing substrates, alternative possibilities for the oxidizing agent must be considered.
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PMID:Reducing substrate activity of some aromatic amines for prostaglandin H synthase. 310 98

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.
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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

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.
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PMID:Peroxidase catalyzed aggregation of plasmid pBR322 DNA by benzidine metabolites in vitro. 374 27

Benzidine is oxidized by the peroxidase/H2O2 system, yielding reactive intermediates. In the presence of thiols, covalent adducts are formed. We used h.p.l.c. to separate the products of the reaction of benzidine with N-acetylcysteine. The major product was identified by n.m.r. spectroscopy (1H-n.m.r.) as 3-(N-acetylcystein-S-yl)-benzidine.
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PMID:Identification of the N-acetylcysteine conjugate of benzidine formed in the peroxidase activation system. 396 36

[14C]Benzidine is rapidly oxidized by a peroxidase/H2O2 system to products which bind irreversibly to DNA. The presence of exogenous DNA also prevented benzidine polymerization to 'benzidine brown' and azobenzidine. Two molar equivalents of H2O2 were required to oxidize the benzidine and achieve maximal DNA binding. Furthermore, 95% of the benzidine was trapped and 36 nmol benzidine was bound per mg DNA. Polyriboguanylic acid was as effective as DNA in binding benzidine, but polyriboadenylic acid, polyribouridylic acid and polyribocytidylic acid were much less effective. Binding of [14C]benzidine correlated well with the absorbance at 295 nm and 390 nm of the modified DNA or various synthetic homopolymers of ribonucleotides isolated from the reaction mixture. The peroxidase/H2O2 system also catalyzed the binding of dichlorobenzidine, o-tolidine and o-dianisidine to DNA but 3,5,3',5'-tetramethylbenzidine, a non-carcinogen, did not bind. The binding could be prevented by various biological hydrogen donors, thiols, or phenolic antioxidants. The mechanisms for DNA protection were investigated; the oxidized benzidine species involved in binding can be reduced with ascorbate, NADPH, or thiols, and trapped by thiols or phenolic antioxidants to form conjugates or adducts.
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PMID:Peroxidase-catalyzed benzidine binding to DNA and other macromolecules. 402 87

Benzidine and related compounds are well known substrates for horseradish peroxidase/H2O2 oxidation. Typically, two different colored products are formed. In this paper, we study the oxidation of 3,5,3',5'-tetramethylbenzidine. The first colored product is a blue charge-transfer complex of the parent diamine and the diimine oxidation product. This species exists in rapid equilibrium with the radical cation. The radical was observed by ESR spectroscopy, and hyperfine splitting constants were determined. Addition of equimolar hydrogen peroxide yields the yellow diimine, which is stable at acid pH. At less than equimolar peroxide, all four species (diamine, radical cation, charge-transfer complex, and diimine) exist in equilibrium. A theoretical analysis of this redox system is presented, including a determination of the extinction coefficients and equilibrium constant for the nonradical species.
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PMID:The horseradish peroxidase-catalyzed oxidation of 3,5,3',5'-tetramethylbenzidine. Free radical and charge-transfer complex intermediates. 627 43


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