XXII. BIOCHEMICKÝ ZJAZD - Jesseniova lekárska fakulta

Posters
120.
SIMILarITY BETWEEN raT AND HUMAN ENZYMES INVOLVED IN
OXIDATION 2-NITROPHENOL, a METABOLITE OF CarCINOGENIC
2-NITROANISOLE
Martina Svobodová, Markéta Martínková, Helena Dračínská and Marie Stiborová
Department of Biochemistry, Faculty of Science, Charles University in Prague
2-Nitrophenol (2-NP) is the main detoxication metabolite of 2-nitroanisole (2-NA) that
is an important industrial pollutant and a potent carcinogen for rodents. The aim of this
study was to investigate the efficiency of rat and human hepatic cytochromes P450 (CYPs)
to metabolize 2-NP, to determine the metabolites formed during such a metabolism and
to compare the efficiencies of rat CYPs with those of human. 2-NP is oxidized by both
liver microsomes to one metabolite, 2,5-dihydroxynitrobenzene (2,5-DNB). To define
the role of rat CYPs in 2-NP oxidation we investigated the modulation of this reaction
by specific inducers and selective inhibitors of these enzymes. Using microsomes from
Baculovirus transfected insect cells expressing recombinant rat and human CYP enzymes,
we found that rat recombinant CYP2E1, 2C11, 2B1, 1A2, 1A1 and 3A4 were the most
effective to oxidize 2-NP. Similarly, human CYP2E1, followed by CYP2A6, 2C6, 3A4 and
2D6 were the most efficient to oxidize 2-NP. In addition, kinetics of oxidation of 2-NP by
the most efficient enzyme catalyzing this reaction, CYP2E1, was investigated. The present
study shows the similarity between human and rat hepatic enzymes metabolizing
2-NP to 2,5-DNB and indicate that rat might serve as a suitable model to mimic the fate
of 2-NP in human.
Acknowledgements: Supported by GACR (303/09/0472) and the Czech Ministry of
Education (MSM 0021620808).
XXII. Biochemistry Congress, Martin
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