Mechanism of Metal-Mediated Oxidative DNA Damage.
Mechanism of Metal-Mediated Oxidative DNA Damage.
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金属介导的氧化 DNA 损伤机制。
DOI：
10.1248/jhs1956.41.399
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Y. Hiraku
中科院分区：
文献类型：
--
作者：
S. Kawanishi;Y. Hiraku
我们研究了致癌金属化合物引起的DNA氧化损伤的机制。铬酸盐（VI）、镍（II）、钴（II）、铁（III）-次氮基三乙酸盐和铜（II）在过氧化氢（H2 O2）存在下诱导DNA损伤产生活性氧物质。内源性还原剂如抗坏血酸、NADH和谷胱甘肽可增强DNA损伤。用δ-氨基乙酰丙酸研究了铅致癌的间接机制，在Cu（II）存在下，δ-氨基乙酰丙酸引起DNA损伤。在此基础上，对活性氧介导的金属致癌机制进行了综述。我们还研究了金属离子和“非诱变性”致癌物相互作用引起的DNA损伤机制。苯醌及其衍生物，如苯，邻苯基苯酚，五氯苯酚和对二氯苯的代谢产物引起Cu（II）依赖的DNA损伤通过H2 O2的产生通过苯醌衍生物的氧化还原循环，需要还原NADH。色氨酸代谢产物和咖啡酸诱导Cu（II）介导的DNA损伤通过H2 O2的形成，这是增强预孵育与Mn（II）。因此，大多数“非诱变性”致癌物产生H2 O2，导致金属依赖性DNA损伤。
We investigated mechanisms of oxidative DNA damage caused by carcinogenic metal compounds. Chromate (VI), nickel (II), cobalt (II), iron (III)-nitrilotriacetate and copper (II) induced DNA damage generating active oxygen species in the presence of hydrogen peroxide (H2O2). DNA damage was enhanced by endogenous reductants such as ascorbate, NADH and glutathione. An indirect mechanism of carcinogenesis by lead was studied using δ-aminolevulinic acid, which caused DNA damage in the presence of Cu (II). On the basis of these findings, we reviewed the mechanism of metal carcinogenesis mediated by active oxygen species. We also studied a mechanism of DNA damage induced by the interaction of metal ions and "non-mutagenic" carcinogens. Benzoquinone and its derivatives such as metabolites of benzene, o-phenylphenol, pentachlorophenol and p-dichlorobenzene caused Cu (II)-dependent DNA damage via H2O2 generation through a redox cycle of benzoquinone derivatives which required NADH for reduction. Tryptophan metabolites and caffeic acid induced Cu (II)-mediated DNA damage through H2O2 formation, which was enhanced by preincubation with Mn (II). It can be concluded that most of "non-mutagenic" carcinogens generate H2O2, which causes metal-dependent DNA damage.