Flavonoids as enhancers of x-ray-induced cell damage in hepatoma cells

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.