Cytochrome P-450 and Peroxidase Oxidize Detoxication Products of Carcinogenic Aristolochic Acids (Aristolactams) to Reactive Metabolites Binding to DNA in vitro

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Title:Cytochrome P-450 and Peroxidase Oxidize Detoxication Products of Carcinogenic Aristolochic Acids (Aristolactams) to Reactive Metabolites Binding to DNA in vitro
Creators:
Stiborová, Marie
Frei, Eva
Schmeiser, Heinz H.
Wiessler, Manfred
Journal or Publication Title:
Collection of Czechoslovak Chemical Communications, 60, 12, pp. 2189-2199

Abstract

<p>We report the analysis of DNA adducts formed from aristolactams I and II, which are the final metabolites derived from carcinogenic aristolochic acids in vivo, after their oxidation by microsomal cytochrome P-450 and horseradish peroxidase in vitro. DNA adducts were detected and quantified using the nuclease P1-enhanced variation of the <sup>32</sup>P-postlabeling assay. Quantitative analysis revelead that the extent of modification of DNA by aristolactams activated by peroxidase was more than one order of magnitude higher than for activation by microsomal cytochrome P-450. Peroxidase catalyzes the formation of active oxygen in the presence of NADH, H<sub>2</sub>O<sub>2</sub> and aristolactams. Aristolactams are also oxidized by mammalian peroxidase prostaglandin H synthase. The possible role of aristolactams in carcinogenesis induced by aristolochic acid is discussed.

Title:Cytochrome P-450 and Peroxidase Oxidize Detoxication Products of Carcinogenic Aristolochic Acids (Aristolactams) to Reactive Metabolites Binding to DNA in vitro
Creators:
Stiborová, Marie
Frei, Eva
Schmeiser, Heinz H.
Wiessler, Manfred
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:60
Number:12
Page Range:pp. 2189-2199
ISSN:0010-0765
E-ISSN:1212-6950
Publisher:Institute of Organic Chemistry and Biochemistry
Related URLs:
URLURL Type
http://dx.doi.org/10.1135/cccc19952189UNSPECIFIED
ID Code:908
Item Type:Article
Deposited On:06 Feb 2009 17:04
Last Modified:06 Feb 2009 16:05

Citation

Stiborová, Marie; Frei, Eva; Schmeiser, Heinz H.; Wiessler, Manfred (1995) Cytochrome P-450 and Peroxidase Oxidize Detoxication Products of Carcinogenic Aristolochic Acids (Aristolactams) to Reactive Metabolites Binding to DNA in vitro. Collection of Czechoslovak Chemical Communications, 60 (12). pp. 2189-2199. ISSN 0010-0765

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