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

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 研究中心，而研究中心不一定是研究者所在的机构。 这些实验的动机是检查铜螯合药物在治疗前列腺癌中的潜在应用的作用模式。 样品由Karmanos癌症研究所的Dou博士小组制备，安装在专门设计的样品架上并运送到BioCAT。两种正常组织样品（仅用溶剂处理和用CQ处理）中的Cu含量显示出相等的Cu含量。用溶剂处理的肿瘤样品仅显示出Cu含量的显著增加，这可能与肿瘤细胞的活性相关。肿瘤组织中的铜含量是正常组织的2 ~ 4倍。与正常组织相比，用CQ处理的肿瘤样品显示出规则的Cu含量。这些图谱证实，与正常组织相比，肿瘤细胞含有显著过量的Cu，并且CQ具有抗癌细胞活性。还获得了形态图，以确定在不同位置的铜的氧化态。 Cu（I）化合物在8983 eV处显示出突出的边缘前峰，这是该氧化态（1 s->4p跃迁）的特征。这一特征不存在于Cu（II）化合物中，其在8978 eV处显示出弱的边缘前峰。 使用这些光谱“特征”，可以确定CQ在肿瘤组织中的抗癌活性涉及改变样品中Cu的氧化态。

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.