XXII. BIOCHEMICKÝ ZJAZD - Jesseniova lekárska fakulta

Posters
112.
oxidaTION of 3-aMINOBENZaNTrONE, a HUMan METaBOLITE of
carCINOGENIC 3-NITrOBENZaNTHrONE, BY HUMan aND
RAT CYTOCHrOMES P450
Jana Mizerovská 1 , Helena Dračínská 1 , Volker M. Arlt 2 , Heinz H. Schmeiser 3 ,
Eva Frei 3 and Marie Stiborová 1
1
Department of Biochemistry, Faculty of Science, Charles University, Albertov 2030,
128 40 Prague 2, Czech Republic, 2 Section of Molecular Carcinogenesis, Institute of
Cancer Research, Brookes Lawley Building, Sutton, Surrey SM2 5NG, United Kingdom,
3
German Cancer Research Center, 69 120 Heidelberg
3-Aminobenzanthrone (3-ABA) is the main reductive metabolite of the carcinogenic
environmental pollutant 3-nitrobenzanthrone (3-NBA). 3-ABA was detected in the urine
samples of salt mining workers exposed to diesel emissions, indicating that exposure to
3-NBA can be detectable. In addition, both parental 3-NBA and its metabolite, 3-ABA,
were found to induce biotransformation enzymes such as cytochrome P450 1A1 and
NAD(P)H:quinone oxidoreductase (NQO1) in several tissues of rats i.p. treated with
both compounds.
Oxidation of 3-ABA was studied using human and rat recombinant CYP enzymes. The
most potent enzymes oxidizing 3-ABA were identified to be CYP1A1 and CYP3A. Using
these enzymes, the kinetic parameters such as K m
and V max
were determined. Here we
also investigate the induction potential of 3-NBA to induce NQO1 and CYP1A1 in rats,
after the 3-NBA intratracheal instillation. Expression of NQO1 and CYP1A1 protein and
its enzymatic activity were induced by 3-NBA in liver, kidney and lung tissues of rats
treated i.t. with a single dose of 0.2 and 2 mg/kg bw of 3-NBA.
Acknowledgments: Supported by GACR (303/09/0472, 203/09/0812 and 305/09/H008)
and the Czech Ministry of Education (MSM 0021620808).
XXII. Biochemistry Congress, Martin
237