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。所列机构为 中心，不一定是研究者的机构。 金属含量分布映射和微X射线吸收光谱在锌K边缘已进行MDA乳腺肿瘤组织。正常组织样品和肿瘤组织样品都显示出相等的Cu含量。未观察到Cu含量的显著增加或减少。这表明肿瘤发育和生长所需的Cu含量的变化并不比正常可用的Cu大得多。DSF在体外可以结合Cu和Zn离子，对Cu具有更高的亲和力，尽管细胞中的Zn含量约为细胞Cu含量的10倍。因此，铜和锌对DSF存在潜在的竞争。我们已经进行了XANES测量在Zn K边缘，以评估DSF在体内与正常和肿瘤细胞的相互作用。XANES光谱中白色线的第一和第二特征表明，与正常组织相比，Zn在肿瘤中明显处于不同的配体环境中。正常和肿瘤DSF处理的组织呈现出相似的XANES模式，表明DSF有效地与细胞Zn相互作用。在这两种情况下，与未经处理的组织相比，第一特征的强度都会降低。这清楚地表明，DSF与正常和肿瘤组织中的细胞Zn相互作用，形成在两个组织切片中观察到的DSF-Zn络合物m。

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. Metal content distribution mapping and micro x-ray absorption spectroscopy at the Zn K edge has been performed on MDA breast tumor tissues. Both normal tissue samples and tumor tissue samples show an equivalent Cu content. No significant increase or decrease in Cu content has been observed. This indicates the variation in Cu content required for tumor development and growth is not much larger than the normal available Cu. DSF can bind to both Cu and Zn ions in vitro with higher affinity for Cu, although Zn content in cells is about 10 fold the content of cellular Cu. Thus, there is a potential competition between Cu and Zn for DSF. We have performed XANES measurements at the Zn K edge in order to evaluate the interaction of DSF in vivo with normal and tumor cells. First and second features of the white line in XANES spectra indicate that Zn is clearly in a different ligand environment in tumor compared with normal tissue. Both normal and tumor DSF treated tissues present similar XANES patterns indicating that DSF effectively interacts with cellular Zn. In both cases the intensity of the first feature decreases compared to the untreated tissue. This clearly shows that DSF interact with cellular Zn in normal and tumor tissue forming a DSF-Zn complex m which is observed in both tissue sections.