EFFECT OF STRUCTURALLY RELATED FLAVONES ISOFLAVONES ON HYDROGEN-PEROXIDE PRODUCTION AND OXIDATIVE DNA-DAMAGE IN PHORBOL ESTER-STIMULATED HL-60 CELLS/

We have examined the antioxidant properties of structurally related fl avones/isoflavones in 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimu lated HL-60 cells. In the presence of 1.3% dimethyl sulfoxide in the m edium for seven days, promyelocytic HL-60 cells were differentiated in to neutrophil-like cells possessing phagocytic properties and the capa city to generate H2O2 on TPA stimulation. The effects of five selected flavones/isoflavones on the formation of H2O2 and 8-hydroxy-2'-deoxyg uanosine (8-OHdG) were examined in TPA-stimulated HL-60 cells. The res ults indicated that genistein was the most potent inhibitor of H2O2 Pr oduction by TPA-stimulated HL-60 cells followed by apigenin and daidze in whereas prunectin and biochanin A exhibited no effect. This inhibit ory effect correlates well with the scavenging capacity of H2O2 by the se flavones/isoflavones in an in vitro system. The formation of 8-OHdG in cellular DNA of HL-60 cells was induced by TPA and further enhance d by the addition of FeCl2 to the medium. Most flavones/isoflavones si gnificantly inhibited TPA + FeCl2-induced 8-OHdG formation in HL-60 ce lls, with genistein being the most potent quencher The inhibition of H 2O2 production and 8-OHdG formation by these structurally related flav ones/isoflavones may contribute to their chemopreventive potentials ag ainst human cancers.