Carcinogenic pollutants o-nitroanisole and o-anisidine are substrates and inducers of cytochromes P450
Language English Country Czech Republic Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
16601807
DOI
10.5507/bp.2005.077
Knihovny.cz E-resources
- MeSH
- Aniline Compounds pharmacokinetics pharmacology MeSH
- Anisoles pharmacokinetics pharmacology MeSH
- Enzyme Induction MeSH
- Carcinogens pharmacokinetics pharmacology MeSH
- Rabbits MeSH
- Rats MeSH
- Environmental Pollutants pharmacokinetics pharmacology MeSH
- Microsomes enzymology MeSH
- Rats, Wistar MeSH
- Cytochrome P-450 Enzyme System biosynthesis MeSH
- Animals MeSH
- Check Tag
- Rabbits MeSH
- Rats MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- 2-anisidine MeSH Browser
- 2-nitroanisole MeSH Browser
- Aniline Compounds MeSH
- Anisoles MeSH
- Carcinogens MeSH
- Environmental Pollutants MeSH
- Cytochrome P-450 Enzyme System 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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