CHARACTERIZATION OF FLAVONOIDS AS MONOFUNCTIONAL OR BIFUNCTIONAL INDUCERS OF QUINONE REDUCTASE IN MURINE HEPATOMA-CELL LINES

The ability of flavonoid compounds to induce the activity of the phase II anticarcinogenic marker enzyme, quinone reductase (QR), has been s tudied in a wild-type murine hepatoma cell line (Hepalclc7) and in an Ah-receptor-defective mutant of the same cell line (Hepalclc7 bp(r)cl) . The results showed that 10 (beta-naphthoflavone, kaempferide, tamari xetin, rhamnetin, quercetin, kaempferol, quercetin-4'-glucoside, isorh amnetin, daidzein and genistein) of the 13 flavonoids tested induced Q R activity in the wild-type cells. Only the latter six also showed suc h activity in the bp(r)cl mutant, which indicates that they induce pha se II enzymes directly (monofunctional inducers), whereas the others i nduce phase II enzymes only in cells with an operative Ah receptor sys tem (bifunctional inducers). The metabolism of representatives of mono functional (quercetin) and bifunctional (tamarixetin and rhamnetin) fl avonol inducers were studied in bath wild-type and bp(r)cl cells. In a ll cases, the major metabolites were glucuronides. Quercetin produced identical metabolites in both cell types, whereas one glucuronide of t amarixetin and two glucuronides of rhamnetin were not formed in the mu tant cells. This shows that flavonoids can be mono- or bifunctional in ducers depending on their chemical structure, and that the glucuronida tion pattern of bifunctional inducers is altered by the presence of a functional Ah receptor system. (C) 1998 Elsevier Science Ltd. All righ ts reserved