44E-21 |
Modulation of cytochrome P450-mediated bioactivation of benzo[a]pyrene in human liver derived cells by allyl sulfides |
H. J. KIM, Quality Assessment and Standard Division, Korea Food Research Institute, San 46-1, Baekhyun-dong, Bundang-gu, Sungnam, 463-746, South Korea and H. S. Chun. Allyl sulfides such as diallyl sulfide (DAS), diallyl disulfide (DADS) and diallyl trisulfide (DATS) are typical flavor compounds of Allium vegetables and well known for their inhibitory effects on benzo[a]pyrene (B[a]P)-induced tumorigenesis in animal model. However, the mechanism for antitumorigenic potential of allyl sulfides was mainly focused on the detoxifying enzymes not on the activating enzyme system that catalyze the bioactivation of B[a]P into ultimate reactive metabolite. In this study, the inhibitory effects of allyl sulfides on cytochrome P450 (CYP) 1 isoform (CYP1A1, CYP1A2, CYP1B1), the major B[a]P activating enzymes was examined by assaying the ethoxyresorufin O-deethylase (EROD) activity as a marker enzyme for CYP 1 isoform. Considering the species-specific metabolism of B[a]P, human hepatic tissue derived cell (HepG2) was used as a surrogate for human liver. DADS and DATS inhibited the B[a]P-induced EROD activity by 30 - 90 % and 70 - 95% at 100 - 1,000 ¥ìM concentration, respectively. Allyl sulfides showed the protective effects on B[a]P-induced cytotoxicity as a consequence of inhibition of EROD activity. Allyl sulfides showed the mixed type inhibition pattern on the B[a]P treated microsomal EROD activity. Western blotting results indicated that the B[a]P-inducible CYP1A2 protein was inhibited by 100 - 1,000 ¥ìM of DADS and 10 - 100 ¥ìM of DATS. However CYP1B1 was not induced by B[a]P treatment. Analysis of B[a]P metabolites revealed that the proportion of 7,8-diol formed was significantly reduced in the DADS and DATS treated microsomes relative to the control (p<0.05). The proportion of 9,10-diol and 4,5-diol formed was also lowered by the allyl sulfides treatment. These results suggest that the mechanism of allyl sulfides on the inhibitory effects of tumorigenesis by B[a]P was possibly related with the inhibition of B[a]P activating enzyme systems.
Session 44E, Nutraceuticals & Functional Foods
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