title: Modulation of cytochrome P4501-mediated bioactivation of benzo[a]pyrene by volatile allyl sulfides in human hepatoma cells.
abstract: Allyl sulfides such as diallyl sulfide (DAS), diallyl disulfide (DADS), and diallyl trisulfide (DATS), typical flavor components of Allium vegetables, have been shown to inhibit benzo[a]pyrene (B[a]P)-induced carcinogenesis in animal models. As a possible mechanism of this inhibition, the effect of these volatile substances on cytochrome P450 (CYP)1 (CYP1A1, 1A2 and 1B1)-mediated bioactivation of B[a]P was investigated using a human hepatoma cell model (HepG2). DADS and DATS inhibited the B[a]P-induced ethoxyresorufin O-deethylase (EROD) activity, a marker enzyme for CYP1, by 30-90% and 70-95% at 100-1,000 microM concentration, respectively. The cell viability, an indicator of the capacity to inhibit B[a]P bioactivation, was increased by treatments of 100-1,000 microM DADS and 10-100 microM DATS. Immunoblot results indicated that the B[a]P inducible CYP1A2 protein was suppressed by 100-1,000 microM of DADS and 10-100 microM of DATS, but CYP1A1 and 1B1 were not detectable in any microsomes. Analysis of B[a]P metabolites revealed that the level of 7,8-diol formed was significantly reduced in the DADS and DATS treated microsomes as compared to the control. The level of 9,10-diol and 4,5-diol formed was also lowered by the allyl sulfide treatments. These results suggest that the protective mechanism of allyl sulfides on B[a]P-induced carcinogenesis is possibly related with the modulation of CYP1-mediated bioactivation of B[a]P.
authors.affiliation: Korea Food Research Institute, Sungnam. hschun@kfri.re.kr
authors.forename: H S
authors.initials: HS
authors.lastname: Chun
authors.forename: H J
authors.initials: HJ
authors.lastname: Kim
authors.forename: E H
authors.initials: EH
authors.lastname: Choi
mesh_terms: D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000032:analysis; D000490:Allium / Q000737:chemistry; D000498:Allyl Compounds / Q000494:pharmacology*; D001580:Benzopyrenes / Q000493:pharmacokinetics*; D001711:Biotransformation; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000378:metabolism*; D019363:Cytochrome P-450 CYP1A1 / Q000032:analysis / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D065609:Cytochrome P-450 CYP1A2 Inhibitors; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D013440:Sulfides / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D000498:Allyl Compounds; D001580:Benzopyrenes; D065609:Cytochrome P-450 CYP1A2 Inhibitors; D065607:Cytochrome P-450 Enzyme Inhibitors; D007527:Isoenzymes; D013440:Sulfides; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; C038491:allyl sulfide; D003577:Cytochrome P-450 Enzyme System; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2