COPPER SPATIAL DISTRIBUTION, CONCENTRATION & STATUS IN NORMAL & TUMOR TISSUES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这些实验的动机是为了研究一种铜螯合药物的作用模式，以期在前列腺癌治疗中得到潜在的应用。样品由Karmanos癌症研究所的Dou博士团队准备，安装在专门设计的样品架上，并被运送到BioCAT。两种正常组织中的铜含量(仅用溶剂处理和用CQ处理)的铜含量相同。用溶剂处理的肿瘤标本只显示铜含量显着增加，这可能与肿瘤细胞的活性有关。肿瘤组织中的铜含量是正常组织的2~4倍。CQ处理的肿瘤标本与正常组织相比，铜含量正常。这些图谱证实，与正常组织相比，肿瘤细胞含有明显过量的铜，CQ具有抗肿瘤细胞活性。还获得了形态图，以确定铜在不同位置的氧化状态。铜(I)化合物在8983 eV处有明显的前缘峰，这是该氧化状态(1s-gt；4p转变)的特征。在8978 eV处出现弱的前缘峰的铜(II)化合物中不存在这一特征。利用这些光谱“信号”，可以确定CQ在肿瘤组织中的抗癌活性涉及改变样品中铜的氧化状态。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The motivation of these experiments was to examine the mode of action of a copper-chelating drug for potential applications in treating prostate cancer. Samples were prepared by Dr. Dou group at Karmanos Cancer Institute, mounted on specially design sample holders and transported to BioCAT. The Cu content in both normal tissue samples (treated with solvent only and treated with CQ) showed an equivalent Cu content. The tumor sample treated with solvent only shows a significant increase in Cu content that can be correlated with the activity of the tumor cells. The Cu content in tumor tissue is 2 to 4 times larger than in normal tissue. The tumor sample treated with CQ showed a regular Cu content compared with normal tissue. These maps confirm that tumor cells contain a significant excess amount of Cu compared with normal tissue and that CQ had anti-cancer cell activity. Speciation maps were also obtained to determine the oxidation state of copper in various locations. Cu(I) compounds showed prominent pre-edge peak at 8983 eV that is characteristic of this oxidation state (1s ->4p transition). This feature was not present in Cu(II) compounds that show a weak pre-edge peak at 8978 eV. Using these spectroscopic "signatures" it was possible to determine that the anti-cancer activity of CQ in tumor tissue involves changing the oxidation state of Cu in the sample.