Catechol and Hydroquinone Have Different Redox Properties Responsible for Their Differential DNA-damaging Ability

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• 作者：Kazutaka Hirakawa ; Shinji Oikawa ; Yusuke Hiraku ; Iwao Hirosawa ; and Shosuke Kawanishi
• 刊名：Chemical Research in Toxicology
• 出版年：2002
• 出版时间：January 2002
• 年：2002
• 卷：15
• 期：1
• 页码：76 - 82
• 全文大小：155K
• 年卷期：v.15,no.1(January 2002)
• ISSN：1520-5010

文摘

We examined the redox properties of the "carcinogenic" catechol and the "noncarcinogenic"hydroquinone in relation to different DNA damaging activities and carcinogenicity using ³²P-labeled DNA fragments obtained from the human genes. In the presence of endogenous NADHand Cu²⁺, catechol induces stronger DNA damage than hydroquinone, although the magnitudesof their DNA damaging activities were reversed in the absence of NADH. In both cases, DNAdamage resulted from base modification at guanine and thymine residues in addition to strandbreakage induced by Cu⁺ and H₂O₂, generated during the oxidation of catechol and hydroquinone into 1,2-benzoquinone and 1,4-benzoquinone, respectively. EPR and ¹H NMR studiesindicated that 1,2-benzoquinone is converted directly into catechol through a nonenzymatictwo-electron reduction by NADH whereas 1,4-benzoquinone is reduced into hydroquinonethrough a semiquinone radical intermediate through two cycles of one-electron reduction. Thereduction of 1,2-benzoquinone by NADH proceeds more rapidly than that of 1,4-benzoquinone.This study demonstrates that the rapid 1,2-benzoquinone two-electron reduction acceleratesthe redox reaction turnover between catechol and 1,2-benzoquinone, resulting in the enhancement of DNA damage. These results suggest that the differences in NADH-mediated redoxproperties of catechol and hydroquinone contribute to their different carcinogenicities.