Yannai S, Day A J, Williamson G, Rhodes M J
Biochemistry Department, Institute of Food Research, Norwich Research Park, Colney, UK.
Food Chem Toxicol. 1998 Aug;36(8):623-30. doi: 10.1016/s0278-6915(98)00022-2.
The ability of flavonoid compounds to induce the activity of the phase II anticarcinogenic marker enzyme, quinone reductase (QR), has been studied 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, tamarixetin, rhamnetin, quercetin, kaempferol, quercetin-4'-glucoside, isorhamnetin, daidzein and genistein) of the 13 flavonoids tested induced QR activity in the wild-type cells. Only the latter six also showed such activity in the bp(r)cl mutant, which indicates that they induce phase II enzymes directly (monofunctional inducers), whereas the others induce phase 11 enzymes only in cells with an operative Ah receptor system (bifunctional inducers). The metabolism of representatives of monofunctional (quercetin) and bifunctional (tamarixetin and rhamnetin) flavonol inducers were studied in both wild-type and bp(r)cl cells. In all cases, the major metabolites were glucuronides. Quercetin produced identical metabolites in both cell types, whereas one glucuronide of tamarixetin and two glucuronides of rhamnetin were not formed in the mutant cells. This shows that flavonoids can be mono- or bifunctional inducers depending on their chemical structure, and that the glucuronidation pattern of bifunctional inducers is altered by the presence of a functional Ah receptor system.
黄酮类化合物诱导II期抗癌标志物酶醌还原酶（QR）活性的能力，已在野生型小鼠肝癌细胞系（Hepalclc7）和同一细胞系的Ah受体缺陷型突变体（Hepalclc7 bp(r)cl）中进行了研究。结果显示，所测试的13种黄酮类化合物中有10种（β-萘黄酮、山柰苷、 tamarixetin、鼠李素、槲皮素、山柰酚、槲皮素-4'-葡萄糖苷、异鼠李素、大豆苷元和染料木黄酮）在野生型细胞中诱导了QR活性。只有后六种在bp(r)cl突变体中也表现出这种活性，这表明它们直接诱导II期酶（单功能诱导剂），而其他的仅在具有有效Ah受体系统的细胞中诱导II期酶（双功能诱导剂）。在野生型和bp(r)cl细胞中都研究了单功能（槲皮素）和双功能（tamarixetin和鼠李素）黄酮醇诱导剂代表物的代谢。在所有情况下，主要代谢产物都是葡萄糖醛酸苷。槲皮素在两种细胞类型中产生相同的代谢产物，而tamarixetin的一种葡萄糖醛酸苷和鼠李素的两种葡萄糖醛酸苷在突变细胞中未形成。这表明黄酮类化合物可根据其化学结构成为单功能或双功能诱导剂，并且双功能诱导剂的葡萄糖醛酸化模式会因功能性Ah受体系统的存在而改变。
