Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2005, 149(2):441-447 | DOI: 10.5507/bp.2005.077

CARCINOGENIC POLLUTANTS o-NITROANISOLE AND o-ANISIDINE ARE SUBSTRATES AND INDUCERS OF CYTOCHROMES P450

Helena Rýdlová, Markéta Mikšanová, Helena Ryšlavá, Marie Stiborová
Department of Biochemistry, Faculty of Science, Charles University, Albertov 2030, 12840 Prague 2, Czech Republic

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.

Keywords: o-Nitroanisole, o-Anisidine, Carcinogen, Cytochromes P450, Induction

Received: June 10, 2005; Accepted: September 25, 2005; Published: December 1, 2005  Show citation

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Rýdlová, H., Mikšanová, M., Ryšlavá, H., & Stiborová, M. (2005). CARCINOGENIC POLLUTANTS o-NITROANISOLE AND o-ANISIDINE ARE SUBSTRATES AND INDUCERS OF CYTOCHROMES P450. Biomedical papers, 149(2), 441-447. doi: 10.5507/bp.2005.077
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