Mechanism of oxidative DNA damage induced by quercetin in the presence of Cu(II)

Quercetin, one of flavonoids, has been reported to be carcinogenic. There h ave been no report concerning carcinogenicity of kaempferol and luteolin wh ich have structure similar to quercetin. DNA damage was examined by using D NA fragments obtained from the human p53 tumor suppressor gene. Quercetin i nduced extensive DNA damage via reacting with Cu(II), but kaempferol and lu teolin induced little DNA damage even in the presence of Cu(LT). Excessive quercetin inhibited copper-dependent DNA damage induced by quercetin. Batho cuproine, a Cu(I)-specific chelator, catalase and methional inhibited the D NA damage by quercetin, whereas free hydroxyl radical scavengers did not. S ite specificity of the DNA damage was thymine and cytosine residues. The si te specificity and the inhibitory effects suggested that DNA-copper-oxygen complex rather than free hydroxyl radical induced the DNA damage. Formation of 8-oxodG by quercetin increased extensively in the presence of Cu(II), w hereas 8-oxodG formation by kaempferol or luteolin increased only slightly. This study suggests a good relationship between carcinogenicity and oxidat ive DNA damage of three flavonoids. The mechanism of DNA damage by querceti n was discussed in relation to the safety in cancer chemoprevention by flav onoids. (C) 1999 Elsevier Science B.V. All rights reserved.