Analysis of heat-labile sites generated by reactions of depleted uranium and ascorbate in plasmid DNA.
Analysis of heat-labile sites generated by reactions of depleted uranium and ascorbate in plasmid DNA.
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DOI：
10.1007/s00775-013-1057-6
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发表时间：
2014-01
影响因子：
3
通讯作者：
Stearns, Diane M.
中科院分区：
文献类型：
--
作者：
Wilson, Janice;Young, Ashley;Civitello, Edgar R.;Stearns, Diane M.
本研究的目的是描述贫铀（DU）如何引起DNA损伤。开发了评估有机和无机DNA加合物在加热或哌啶存在下转化为pBR 322质粒DNA中单链断裂（SSB）的能力的程序。将甲基甲磺酸酯（MMS）、顺铂（cis-Pt）和氯化铬形成的DNA加合物与乙酸铀酰（UA）和抗坏血酸（Asc）反应形成的DNA加合物进行比较。铀酰离子在Asc存在下产生U-DNA加合物，其在加热时转化为SSB。双胍作用于MMS甲基化的DNA，将甲基-DNA加合物转化为SSB，通过减少SSB以相反的方式与U-DNA加合物作用。观察到哌啶也降低了由单官能顺式铂和氯化铬形成的金属-DNA加合物的凝胶位移，解释为表明哌啶用于去除U-DNA加合物。自由基清除剂不影响U诱导的SSB的形成，这表明SSB产生的U-DNA加合物的存在下，而不是从自由基。提出了一个模型来预测如何U-DNA加合物可能作为初始病变转换为SSB或AP网站。结果表明，贫铀可以作为一种化学遗传毒素，其作用方式不需要辐射。描述DU形成的DNA损伤对于评估不同DNA损伤在DU诱导突变形成中的相对重要性是必要的。了解贫铀诱发突变的形成机制可能有助于确定人类贫铀暴露的生物标志物。
The goal of this study was to characterize how depleted uranium (DU) causes DNA damage. Procedures were developed to assess the ability of organic and inorganic DNA adducts to convert to single strand breaks (SSB) in pBR322 plasmid DNA in the presence of heat or piperidine. DNA adducts formed by methyl methanesulfonate (MMS), cis-platin (cis-Pt), and chromic chloride were compared to those formed by reaction of uranyl acetate (UA) and ascorbate (Asc). Uranyl ion in the presence of Asc produced U-DNA adducts that converted to SSB upon heating. Piperidine, which acted on DNA methylated by MMS to convert methyl-DNA adducts to SSB, served in the opposite fashion with U-DNA adducts by decreasing SSB. The observation that piperidine also decreased the gel shift for metal-DNA adducts formed by monofunctional cis-Pt and chromic chloride was interpreted to suggest that piperidine served to remove U-DNA adducts. Radical scavengers did not affect formation of U-induced SSB, suggesting that SSB arose from the presence of U-DNA adducts and not from free radicals. A model is proposed to predict how U-DNA adducts may serve as initial lesions that convert to SSB or AP sites. Results suggest that DU can act as a chemical genotoxin that does not require radiation for its mode of action. Characterizing the DNA lesions formed by DU is necessary to assess the relative importance of different DNA lesions in the formation of DU-induced mutations. Understanding mechanisms of formation of DU-induced mutations may contribute to identification of biomarkers of DU exposures in humans.
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DOI：
10.1016/j.mrgentox.2009.05.006
发表时间：
2009-08
影响因子：
1.9
作者：
Boysen, Gunnar;Pachkowski, Brian F.;Nakamura, Jun;Swenberg, James A.
通讯作者：
Swenberg, James A.
影响因子：
4.1
作者：
Blankert, SA;Coryell, VH;Stearns, DM
通讯作者：
Stearns, DM
影响因子：
3.5
作者：
Darolles, C.;Broggio, D.;Petitot, F.
通讯作者：
Petitot, F.
影响因子：
2.9
作者：
EASTMAN, A
通讯作者：
EASTMAN, A
影响因子：
4.6
作者：
Galindo, Miguel A.;Amantia, David;Houlton, Andrew
通讯作者：
Houlton, Andrew