van Rijn J, van den Berg J
Department of Radiotherapy, Academic Hospital Vrije Universiteit, Amsterdam, the Netherlands.
Clin Cancer Res. 1997 Oct;3(10):1775-9.
The nuclear enzyme topoisomerase II, which is involved in replication, transcription, and probably repair of DNA, can be inhibited by a number of flavonoids. In conjunction with X-rays, three of these compounds were tested as to their effects on Reuber H35 hepatoma cells. In this combination, the isoflavone genistein, the flavone apigenin, and the flavonol quercetin caused an enhancement of radiation-induced cell death. This enhanced cytotoxicity was only observed when the flavonoids were applied following an irradiation treatment and is attributed to decreased repair of DNA radiation damage with a concomitant reduction of the rate of cell repopulation. Fractionated irradiations, given as five sequences of 3 Gy each over a period of 5 days, reduced the surviving cell population only by a factor of 20, whereas the continuous presence of genistein during radiation sequences resulted in a reduction of at least a factor of 10,000. Thus, these flavonoids not only seem to act as radiation enhancers but also exhibit potential antitumor activities.
核酶拓扑异构酶II参与DNA的复制、转录以及可能的修复过程，它能被多种黄酮类化合物抑制。与X射线联合使用时，测试了其中三种化合物对鲁伯H35肝癌细胞的影响。在这种联合作用下，异黄酮染料木黄酮、黄酮芹菜素和黄酮醇槲皮素会增强辐射诱导的细胞死亡。只有在照射处理后应用黄酮类化合物时，才会观察到这种增强的细胞毒性，这归因于DNA辐射损伤修复减少以及细胞再增殖速率同时降低。分次照射，在5天内分5次每次给予3 Gy，仅使存活细胞群体减少了20倍，而在照射过程中持续存在染料木黄酮则导致至少减少10000倍。因此，这些黄酮类化合物不仅似乎起到辐射增强剂的作用，还表现出潜在的抗肿瘤活性。
