Toxicity of depleted uranium complexes is independent of p53 activity.
Toxicity of depleted uranium complexes is independent of p53 activity.
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DOI：
10.1016/j.jinorgbio.2010.10.010
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发表时间：
2011-02
影响因子：
3.9
通讯作者：
Gage, Matthew J.
中科院分区：
文献类型：
--
作者：
Heintze, Ellie;Aguilera, Camille;Davis, Malia;Fricker, Avery;Li, Qiang;Martinez, Jesse;Gage, Matthew J.
p53 肿瘤抑制蛋白是细胞对各种应激机制（包括暴露于各种有毒金属复合物）做出反应的关键检查点之一。先前的研究已证明砷和铬络合物能够激活 p53，但缺乏研究铀络合物是否表现出类似作用的数据。近年来，贫铀 (DU) 的使用有所增加，引发了人们对贫铀潜在致癌作用的担忧。先前的研究表明，乙酸双氧铀和硝酸双氧铀能够诱导 DNA 链断裂，并可能通过自由基的产生诱导氧化应激，这是激活 p53 的两种潜在机制。基于这些研究，我们假设乙酸双氧铀或硝酸双氧铀可以充当 p53 的激活剂。我们结合使用细胞毒性测定、p53 活性测定、蛋白质印迹和流式细胞术测试了这一假设。我们所有的结果都表明，对于乙酸双氧铀或硝酸双氧铀都不存在 p53 介导的反应，这表明在研究条件下，任何细胞对铀暴露的反应都可能以不依赖于 p53 的方式发生。
The p53 tumor suppressor protein is one of the key checkpoints in cellular response to a variety of stress mechanisms, including exposure to various toxic metal complexes. Previous studies have demonstrated that arsenic and chromium complexes are able to activate p53, but there is a dearth of data investigating whether uranium complexes exhibit similar effects. The use of depleted uranium (DU) has increased in recent years, raising concern about DU’s potential carcinogenic effects. Previous studies have shown that uranyl acetate and uranyl nitrate are capable of inducing DNA strand breaks and potentially of inducing oxidative stress through free radical generation, two potential mechanisms for activation of p53. Based on these studies, we hypothesized that either uranyl acetate or uranyl nitrate could act as an activator of p53. We tested this hypothesis using a combination of cytotoxicity assays, p53 activity assays, western blotting and flow cytometry. All of our results demonstrate that there is not a p53-mediated response to either uranyl acetate or uranyl nitrate, demonstrating that any cellular response to uranium exposure likely occurs in a p53-independent fashion under the conditions studied.
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镍对人肺细胞细胞周期蛋白表达、细胞周期进展和细胞增殖的影响
DOI：
10.1158/1055-9965.epi-09-0115
发表时间：
2009-06
期刊：
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
影响因子：
--
作者：
Ding J;He G;Gong W;Wen W;Sun W;Ning B;Huang S;Wu K;Huang C;Wu M;Xie W;Wang H
通讯作者：
Wang H
影响因子：
4.3
作者：
Miller, AC;Bonait-Pellie, C;Lison, PD
通讯作者：
Lison, PD
影响因子：
8
作者：
de Toledo, SM;Azzam, EI;Little, JB
通讯作者：
Little, JB
影响因子：
8
作者：
Palecek, E;Brázdová, M;Vojtesek, B
通讯作者：
Vojtesek, B
影响因子：
3.8
作者：
Hill, Richard;Leidal, Andrew M.;Lee, Patrick W. K.
通讯作者：
Lee, Patrick W. K.