Modulation of CYP1A1-mediated oxidation of carcinogenic azo dye Sudan I and its binding to DNA by cytochrome b5
Jazyk angličtina Země Švédsko Médium print
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
17159775
PII: NEL270806A07
Knihovny.cz E-zdroje
- MeSH
- adukty DNA metabolismus MeSH
- barvicí látky farmakokinetika MeSH
- biologické modely MeSH
- cytochrom P-450 CYP1A1 metabolismus MeSH
- cytochromy b5 fyziologie MeSH
- DNA metabolismus MeSH
- I. fáze biotransformace * MeSH
- králíci MeSH
- krysa rodu Rattus MeSH
- lidé MeSH
- naftoly metabolismus farmakokinetika MeSH
- potkani Wistar MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- krysa rodu Rattus MeSH
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- 1-phenylazo-2-naphthol MeSH Prohlížeč
- adukty DNA MeSH
- barvicí látky MeSH
- cytochrom P-450 CYP1A1 MeSH
- cytochromy b5 MeSH
- DNA MeSH
- naftoly MeSH
OBJECTIVES: Modulation of the cytochrome P450 (CYP) 1A1-mediated oxidative activation and detoxication of carcinogenic Sudan I by the heme-protein cytochrome b(5) (b(5)) was investigated. Another aim of the study was to examine the formation of Sudan I-DNA adducts in vivo. METHODS: High performance liquid chromatography (HPLC) with ultraviolet (UV) detection was employed for the separation of Sudan I metabolites formed by human recombinant CYPs and rat CYP1A1. The (32)P-postlabeling technique was utilized to determine Sudan I-DNA adducts. RESULTS: The capabilities of the most efficient CYP enzymes oxidizing Sudan I, human and rat recombinant CYP1A1, as well as of human recombinant CYP1A2, 2A6 and 3A4 were significantly increased by b(5), while reactions catalyzed by human CYP1B1, 2C8, 2C9 and 2E1 were insensitive to this heme protein. Sudan I oxidation catalyzed by CYP2B6, 2C19 and 2D6 was even decreased by b(5). The stimulation of the CYP1A1-mediated Sudan I oxidation was dependent on concentration of b(5). Likewise, the increase in CYP1A1-mediated formation of Sudan I-DNA adducts by b(5) was concentration dependent. Other proteins containing heme such as cytochrome c or myoglobin were without this effect. The major Sudan I-DNA adducts formed in vitro are also generated in vivo, in livers of rats treated with Sudan I. CONCLUSIONS: The data are the first report on the stimulation of CYP1A1-mediated oxidative reactions by b(5). In addition, the results demonstrating covalent binding of Sudan I to rat liver DNA in vivo indicate a genotoxic mechanism of Sudan I carcinogenicity in rats.
Optimalization of preparation of apo-cytochrome b(5) utilizing apo-myoglobin
