We have investigated the effect of the soybean isoflavone genistein on 8-hydroxy-2'-deoxyguanosine (8-OHdG) formation in calf thymus DNA exposed to either UV irradiation or the Fenton reaction system. Under the conditions used we observed that UV light and the Fenton reaction significantly increase 8-OHdG formation in DNA. Co-incubation with genistein inhibits the formation of 8-OHdG induced by either UV light is raddiation or the Fenton reaction in a dose-dependent manner. The quencing effect of genistein on 8-OHdG formation induced by UV light is much more potent than that by the Fenton reaction, suggesting that the mechanisms of 8-OHdG formation may differ between the two systems. We further compared the antioxidant activities and quenching effect on 8-OHdG formation of genistein with biochanin A. Geneistein potently scavenges both hydrogen peroxide in the medium and superoxide anion generated by xanthine/xanthine oxidase, whereas biochanin A has either a weak or no scavenging effect on these reactive oxygen species. However, both geneistein and biochanin A display a similar quenching effect on UV light-induced 8-OHdG formation. These results suggest that the quenching effect of geneistein and biochanin A on UV light-induced 8-OHdG formation is different from their ability to scavenge hydrogen peroxide and superoxide anion. The potent inhibition of UV light-induced oxidative DNA damage by genistein suggests its potential anticarcinogenic role in photocarcinogenesis.