XXII. BIOCHEMICKÝ ZJAZD - Jesseniova lekárska fakulta

Posters
113.
METaBOLIC aCTIvaTION of carCINOGENIC BENZO[a]PYrENE BY
CYTOCHrOME P450 1A1 IS DICTaTED BY COMPOSITION of THE MIXEDfUNCTION-MONOOXYGENaSE
SYSTEM
Michaela Moserová 1 , Miroslav Šulc 1 , Volker M. Arlt 3 , David H. Phillips 3 ,
Eva Frei 2 and Marie Stiborová 1
1
Department of Biochemistry, Charles University, Albertov 2030, 128 40 Prague 2; 2
Department of Molecular Toxicology, German Cancer Research Center,
69 120 Heidelberg; 3 Section of Molecular Carcinogenesis, Institute of Cancer Research,
Brookes Lawley Building, Sutton, Surrey SM2 5NG, UK
Carcinogenic benzo(a)pyrene (BaP) was investigated for its potential to generate DNA
adducts and to induce cytochrome P450 (CYP)and NADPH:CYP reductase (POR) enzymes
in livers.
BaP induces expression of these enzymes in livers of experimental models, which leads to
increase in their enzymatic activity. In addition, this compound is capable of generating
DNA adducts, predominantly in livers of studied organisms. The stimulation effect was
attributed to induction of CYP1A1/2 and/or enzymes, which are responsible for oxidative
activation of BaP to the metabolites generating major DNA adducts in vitro. BaP is
oxidized by hepatic microsomes from pretreated and control animals to six metabolites.
BaP is also oxidized with purified CYP1A1 reconstituted with NADPH:CYP reductase
generating only five metabolites, but forming two DNA adducts. Activation of BaP by
CYP1A1 is dictated by composition of the mixed-function-monooxygenase system of the
endoplasmic reticulum.
Acknowledgments: Supported by Czech Science Foundation (303/09/0472, 305/09/
H008), Grant Agency of Charles University (127208) and Ministry of Education, Youth
and Sports (MSM 0021620808).
238 XXII. Biochemistry Congress, Martin