Modulation of cytochrome P4501-mediated bioactivation of benzo[a]pyrene by volatile allyl sulfides in human hepatoma cells. |
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Authors: | H S Chun H J Kim E H Choi |
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Institution: | Korea Food Research Institute, Sungnam. hschun@kfri.re.kr |
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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 benzoa]pyrene (Ba]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 Ba]P was investigated using a human hepatoma cell model (HepG2). DADS and DATS inhibited the Ba]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 Ba]P bioactivation, was increased by treatments of 100-1,000 microM DADS and 10-100 microM DATS. Immunoblot results indicated that the Ba]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 Ba]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 Ba]P-induced carcinogenesis is possibly related with the modulation of CYP1-mediated bioactivation of Ba]P. |
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