Metabolism of Carcinogenic Azo Dye Sudan I by Rat, Rabbit, Minipig and Human Hepatic Microsomes

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Title:Metabolism of Carcinogenic Azo Dye Sudan I by Rat, Rabbit, Minipig and Human Hepatic Microsomes
Creators:
Martínek, Václav
Stiborová, Marie
Journal or Publication Title:
Collection of Czechoslovak Chemical Communications, 67, 12, pp. 1883-1898
Uncontrolled Keywords:Cytochromes P450, Metabolism, 1-(Phenylazo)-2-naphthol, Mutagenesis, Carcinogenesis, Toxicology, Mechanism of action, Risk assessment, Azo compounds

Abstract

We investigated the ability of hepatic microsomal samples from different species including human to metabolize rodent carcinogen Sudan I (C.I. Solvent Yellow 14, 1-(phenylazo)-2-naphthol). A comparison between experimental animals and the human microsomal enzymatic system is essential for the extrapolation of animal carcinogenicity data to assess human health risk. Major metabolites produced from Sudan I by microsomes of all species were C-hydroxylated derivatives identified as 1-[(4-hydroxyphenyl)azo]-2-naphthol and 1-(phenylazo)naphthalene-2,6-diol. Additional minor C-hydroxylated products of Sudan I oxidation were 1-[(4-hydroxyphenyl)azo]naphthalene-2,6-diol and 1-[(3,4-dihydroxyphenyl)- azo]-2-naphthol. Human microsomes generated the pattern of Sudan I metabolites reproducing that formed by hepatic microsomes of rats. While microsomes of rabbit and minipig favored the production of the metabolite hydroxylated in position 6 of the naphthol ring of the Sudan I molecule, those of human and rat predominantly produced 1-[(4-hydroxyphenyl)azo]-2-naphthol. Therefore, rat microsomes are a suitable <i>in vitro</i> system mimicking the metabolism of Sudan I in humans. To define the role of specific cytochromes P450 in the Sudan I metabolism by rat microsomes, we investigated the modulation of Sudan I oxidation by specific inducers and selective inhibitors of these enzymes. The results suggest that cytochromes P450 1A1 and 3A are responsible for Sudan I metabolism by rat microsomes. Using purified enzymes, their ability to oxidize Sudan I was confirmed. The data clearly demonstrate the predominant role of cytochrome P450 1A1 in the Sudan I metabolism and suggest a carcinogenic potency of this rodent carcinogen for humans. <p>

Title:Metabolism of Carcinogenic Azo Dye Sudan I by Rat, Rabbit, Minipig and Human Hepatic Microsomes
Creators:
Martínek, Václav
Stiborová, Marie
Uncontrolled Keywords:Cytochromes P450, Metabolism, 1-(Phenylazo)-2-naphthol, Mutagenesis, Carcinogenesis, Toxicology, Mechanism of action, Risk assessment, Azo 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:67
Number:12
Page Range:pp. 1883-1898
ISSN:0010-0765
E-ISSN:1212-6950
Publisher:Institute of Organic Chemistry and Biochemistry
Related URLs:
URLURL Type
http://dx.doi.org/10.1135/cccc20021883UNSPECIFIED
ID Code:2040
Item Type:Article
Deposited On:06 Feb 2009 17:15
Last Modified:06 Feb 2009 16:15

Citation

Martínek, Václav; Stiborová, Marie (2002) Metabolism of Carcinogenic Azo Dye Sudan I by Rat, Rabbit, Minipig and Human Hepatic Microsomes. Collection of Czechoslovak Chemical Communications, 67 (12). pp. 1883-1898. ISSN 0010-0765

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