Potent modification of inducible CYP1A1 expression by flavonoids.

The present study examined modifications of β-naphthoflavone (β-NF)-induced cytochrome P450 1A1 (CYP1A1) expression by flavonoids in mouse hepatocytes in primary culture. Some flavonoids (apigenin, chrysin, flavone, flavanone, galangin, luteolin, and naringenin) by themselves induced CYP1A1 mRNA expression, especially flavone which was even more effective than β-NF. The effect on β-NF-induced CYP1A1 mRNA expression was varied, namely additive, suppressive, or both. An additive effect was observed after combined treatment with flavanone, naringenin, and chrysin, whereas kaempferol, myricetin, and quercetin decreased CYP1A1 levels. Apigenin, chrysin, galangin, luteolin, and morin synergistically enhanced β-NF-induced CYP1A1 expression at 24 h, but considerably suppressed it at 9 h. The structure-activity relationship of flavonoids affecting CYP1A1 expression as inducers or inhibitors is discussed. The present observations suggest the need to reveal the mechanism by which CYP1A1 expression is modified by flavonoids for risk assessment, since CYP1A1 activates environmental carcinogenic polycyclic hydrocarbons and flavonoids are major constituents in food.