Inhibition of benzo[a]pyrene-induced cytotoxicity and cytochrome P450 1A activity by dietary flavonoids in human liver cell model: structure-activityrelationship

Inhibition of benzo[a]pyrene (B[a]P)-induced cytotoxicity and cytochrome p4 50 1A (CYP 1A) activity by flavonoids (1-100 muM) was examined in terms of the structure-activity relationship in the human liver-derived cell model ( HepG2). Two hydroxyl groups in the 5- and 7-position of flavonoids were ess ential to inhibit B[a]P-induced cytotoxicity. Generally, flavones (IC50; 5. 0-17.2 muM) were more potent than the corresponding flavonols (IC50; 42.7-1 31.8 muM), and flavonoids such as apigenin (IC50; 7.2 muM) were more active than the corresponding isoflavonoids, genistein (IC50; 61.7 muM). The plan ar structure of flavone proved to be important in inhibiting B[a]P-induced toxicity and CYP 1A activity. The inhibitory effect of flavonoids on B[a]P- induced CYP 1A activity was correlated well with the inhibition of B[a]P-in duced cytotoxicity (r=0.635, p <0.01).