Carcinogenic pollutants o-nitroanisole and o-anisidine are substrates and inducers of cytochromes P450
Jazyk angličtina Země Česko Médium print
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
16601807
DOI
10.5507/bp.2005.077
Knihovny.cz E-zdroje
- MeSH
- aniliny farmakokinetika farmakologie MeSH
- anisoly farmakokinetika farmakologie MeSH
- enzymová indukce MeSH
- karcinogeny farmakokinetika farmakologie MeSH
- králíci MeSH
- krysa rodu Rattus MeSH
- látky znečišťující životní prostředí farmakokinetika farmakologie MeSH
- mikrozomy enzymologie MeSH
- potkani Wistar MeSH
- systém (enzymů) cytochromů P-450 biosyntéza MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- 2-anisidine MeSH Prohlížeč
- 2-nitroanisole MeSH Prohlížeč
- aniliny MeSH
- anisoly MeSH
- karcinogeny MeSH
- látky znečišťující životní prostředí MeSH
- systém (enzymů) cytochromů P-450 MeSH
2-Methoxyaniline (o-anisidine) and 2-methoxynitrobenzene (o-nitroanisole) are important pollutants and potent carcinogens for rodents. o-Anisidine is oxidized by microsomes of rats and rabbits to N-(2-methoxyphenyl)hydroxylamine that is also formed as the reduction metabolite of o-nitroanisole. o-Anisidine is a promiscuity substrate of rat and rabbit cytochrome P450 (CYP) enzymes, because CYPs of 1A, 2B, 2E and 3A subfamilies oxidize o-anisidine. Using purified CYP enzymes, reconstituted with NADPH: CYP reductase, rabbit CYP2E1 was the most efficient enzyme oxidizing o-anisidine, but the ability of CYP1A1, 1A2, 2B2, 2B4 and 3A6 to participate in o-anisidine oxidation was also proved. Utilizing Western blotting and consecutive immunoquantification employing chicken polyclonal anti bodies raised against various CYPs, the effect of o-anisidine and o-nitroanisole on the expression of the CYP enzymes was investigated. The expression of CYP1A1/2 was found to be strongly induced in rats treated with either compounds. In addition, 7-ethoxyresorufin O-deethylation, a marker activity for both CYP1A1 and 1A2, was significantly increased in rats treated with either carcinogen. The data demonstrate the participation of different rat and rabbit CYP enzymes in o-anisidine oxidation and indicate that both experimental animal species might serve as suitable models to mimic the o-anisidine oxidation in human. Furthermore, by induction of rat hepatic and renal CYP1A1/2, both o-nitroanisole and o-anisidine influence their carcinogenic effects, modifying their detoxification and/or activation pathways.
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