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자료유형
학술대회자료
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한국식품영양과학회 한국식품영양과학회 학술대회발표집 한국식품영양과학회 International Symposium 제50차
발행연도
2001.12
수록면
340 - 347 (8page)

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A variety of dietary plant flavonoids and organosulfur compounds have been found to inhibit tumor development in several experimental animal models and to act through different mechanisms. One of the ways flavonoids and organosulfur compounds may inhibit carcinogenesis is by modulating the biotransformation of chemical carcinogens. As a mechanistic study, the effect of these substances on the biotransformation of benzo[a]pyrene (B[a]P) was investigated using human hepatic and extrahepatic cellular models in terms of the structure-activity relationship. Of flavonoids, flavonoids with two hydroxyl groups at the 5- and 7-position were found to inhibit the B[a]P-induced ethoxyresorufin O-deethylase (EROD) activity, a marker enzyme for cytochrome p450 1A (CYP 1A) that playa critical role in B[a]P bioactivation pathways. Flavones were more potent than corresponding flavonols, and flavonoids were more active than the corresponding isoflavonoids, suggesting the planar structure of the flavone is important in inhibiting B[a]P-induced CYP 1A activity. Organosulfur compounds such as diallyl disulfide (DADS) and diallyl trisulfide (DATS) inhibited the B[a]P-induced EROD activity by 30-90% and 70-95% at 100-1,000 μM concentration, respectively, with a mixed type inhibition pattern. Immunoblot results indicated that the B[a]P inducible CYP1A2 protein was suppressed by 100-1,000 μM of DADS and 10-100 μM of DATS. Analysis of B[a]P metabolites revealed that the levels of 7,8-diol, 9,10-diol and 4,5-diol formed were significantly reduced in the DADS and DATS treated microsomes as compared to the control. The allyl group and number of sulfur atoms of organosulfur compounds were found to be essential in dominating their modulatory potentials. In contrast, flavonoids and organosulfur compounds did not induce the activity of glutathione S-transferase (GST), which catalyses conjugation of electrophilic B[a]P metabolites with GSH. As judged by cell viability assay, an indicator of the capacity to detoxify reactive B[a]P metabolites, the cell viability was decreased by the addition of GST inhibitors, ethacrynic acid and ketoprofen, and GSH depletor, diethylmaleate but was increased by the treatment of GST enhancer, 6-propyl-n-thiouracil. Extension of these studies to other electrophile-processing enzyme showed that NAD(P)H:(quinone-acceptor) oxidoreductase (QR) activity was slightly induced by some flavonoids and organosulfur compounds. It is, therefore, implied that the modulatory action on the B[a]P bioactivation by flavonoids and organosulfur compounds may playa role in their chemopreventive activity.

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Abstract

INTRODUCTION

MATERIALS AND METHODS

RESULTS AND DISCUSSION

References

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