To the Mechanism of 2-Nitroanisole Carcinogenicity: in vitro Metabolism of 2-Nitroanisole Mediated by Peroxidasesand Xanthine Oxidase

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Title:To the Mechanism of 2-Nitroanisole Carcinogenicity: in vitro Metabolism of 2-Nitroanisole Mediated by Peroxidasesand Xanthine Oxidase
Creators:
Stiborová, Marie
Schmeiser, Heinz H.
Frei, Eva
Journal or Publication Title:
Collection of Czechoslovak Chemical Communications, 63, 6, pp. 857-869
Uncontrolled Keywords:Radicals, Reduction, DNA adducts, Initiation and promotion phases of carcinogenesis, Oxidation, Carcinogens, Nitro compounds

Abstract

The <i>in vitro</i> enzymatic metabolism of carcinogenic 2-nitroanisole was investigated using peroxidases (horseradish peroxidase and prostaglandin H synthase) and xanthine oxidase catalyzing oxidative and reductive reactions, respectively. The oxidation of 2-nitroanisole catalyzed by horseradish peroxidase exhibits the Michaelis-Menten kinetics. The Michaelis constant (<i>K</i><sub>m</sub>) and the maximal velocity (<i>V</i><sub>max</sub>) values for this substrate were determined at pH 5.0, 7.0, 7.6 and 8.0. At optimal pH (7.6), the <i>K</i><sub>m</sub> and <i>V</i><sub>max</sub> values are 0.219 μmol/l and 34.45 pmol/min per nmol peroxidase, respectively. The oxidation of 2-nitroanisole is inhibited by radical trapping agents (NADH, ascorbate, glutathione and nitrosobenzene). This indicates that the peroxidase-mediated oxidation of 2-nitroanisole proceeds <i>via</i> a radical mechanism. Active oxygen species are formed during the horseradish peroxidase-catalyzed reactions in the presence of NADH, hydrogen peroxide and 2-nitroanisole. 2-Nitroanisole is also oxidized by mammalian prostaglandin H synthase. Using the nuclease P1-enhanced variation of the <sup>32</sup>P-postlabelling assay, the formation of DNA adducts was detected in DNA treated with 2-nitroanisole and xanthine oxidase. No DNA binding was detected after oxidation of 2-nitroanisole with horseradish peroxidase and prostaglandin H synthase. The results presented (the formation of DNA adducts after 2-nitroanisole activation by xanthine oxidase and that of radicals and/or superoxide radicals during the reactions with peroxidases) strongly suggest the participation of 2-nitroanisole both in the initiation and in the promotion phases of carcinogenesis.

Title:To the Mechanism of 2-Nitroanisole Carcinogenicity: in vitro Metabolism of 2-Nitroanisole Mediated by Peroxidasesand Xanthine Oxidase
Creators:
Stiborová, Marie
Schmeiser, Heinz H.
Frei, Eva
Uncontrolled Keywords:Radicals, Reduction, DNA adducts, Initiation and promotion phases of carcinogenesis, Oxidation, Carcinogens, Nitro compounds
Divisions:Life and Chemical Sciences > Institute of Organic Chemistry and Biochemistry > Collection of Czechoslovak Chemical Communications
Journal or Publication Title:Collection of Czechoslovak Chemical Communications
Volume:63
Number:6
Page Range:pp. 857-869
ISSN:0010-0765
E-ISSN:1212-6950
Publisher:Institute of Organic Chemistry and Biochemistry
Related URLs:
URLURL Type
http://dx.doi.org/10.1135/cccc19980857UNSPECIFIED
ID Code:1350
Item Type:Article
Deposited On:06 Feb 2009 17:08
Last Modified:06 Feb 2009 16:08

Citation

Stiborová, Marie; Schmeiser, Heinz H.; Frei, Eva (1998) To the Mechanism of 2-Nitroanisole Carcinogenicity: in vitro Metabolism of 2-Nitroanisole Mediated by Peroxidasesand Xanthine Oxidase. Collection of Czechoslovak Chemical Communications, 63 (6). pp. 857-869. ISSN 0010-0765

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