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[铀酰离子通过活性氧物种的产生对体外DNA的遗传毒性作用]

[The genotoxic action of uranyl ions on DNA in vitro caused by the generation of reactive oxygen species].

作者信息

Smirnova V S, Gudkov S V, Shtarkman I N, Chernikov A V, Bruskov V I

出版信息

Biofizika. 2005 May-Jun;50(3):456-63.

PMID:15977835
Abstract

8-Oxoguanine (8-OG) is an important biomarker of oxidative DNA damage induced by reactive oxygen species (ROS). By using ELISA with monoclonal antibodies against 8-OG, the formation of 8-OG in DNA by the action of uranyl ions, gamma-irradiation, and heating at 37 degrees C and their combined action was investigated in view of environmental pollution by uranium oxides as a result of the use of armor piercing shells with depleted uranium. The content of 8-OG in DNA induced by the action of gamma-irradiation, 5 microM uranyl ions and heating changes with time in a complicated manner. These results suggest that, by the action of uranyl ions, an additional generation of ROS occurs, which leads both to the formation of 8-OG in DNA and its further oxidation. Uranyl ions at a conceptration of 5 microM increase the thermal deamination of cytosine in DNA several times but do not influence DNA thermal depurination. It is shown that uranyl ions essentially increase the production of hydrogen peroxide and hydroxyl radicals by the action of heat on water. The results indicate a high chemical genotoxicity of uranyl ions and their enhancing effect on DNA base damage by the action of heat and gamma-irradiation.

摘要

8-氧代鸟嘌呤(8-OG)是活性氧(ROS)诱导的氧化DNA损伤的重要生物标志物。鉴于使用贫铀穿甲弹导致氧化铀对环境的污染,通过使用针对8-OG的单克隆抗体的酶联免疫吸附测定(ELISA),研究了铀离子、γ射线照射、37℃加热及其联合作用下DNA中8-OG的形成情况。γ射线照射、5μM铀离子作用以及加热诱导的DNA中8-OG含量随时间呈复杂变化。这些结果表明,铀离子作用会额外产生活性氧,这既导致DNA中8-OG的形成,又使其进一步氧化。5μM浓度的铀离子使DNA中胞嘧啶的热脱氨基作用增加数倍,但不影响DNA的热脱嘌呤作用。结果表明,铀离子通过加热作用于水可显著增加过氧化氢和羟基自由基的产生。这些结果表明铀离子具有很高的化学遗传毒性,以及其在加热和γ射线照射作用下对DNA碱基损伤的增强作用。

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