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。 对MDA乳腺肿瘤组织进行了锌K边金属含量分布图和显微X射线吸收光谱分析。正常组织样本和肿瘤组织样本的铜含量相同。没有观察到铜含量的显著增加或减少。这表明肿瘤发生和生长所需的铜含量的变化并不比正常有效铜大很多。DSF在体外可以与铜和锌离子结合，对铜有较高的亲和力，但细胞中的锌含量约为细胞铜含量的10倍。因此，铜和锌之间存在着潜在的DSF竞争。我们在锌K边缘进行了XANES测量，以评估体内DSF与正常细胞和肿瘤细胞的相互作用。XANES光谱中白线的第一和第二特征表明，与正常组织相比，肿瘤组织中的锌明显处于不同的配体环境中。正常组织和经DSF处理的肿瘤组织呈现相似的XANES图谱，表明DSF有效地与细胞内的锌相互作用。在这两种情况下，与未经处理的组织相比，第一个特征的强度降低。这清楚地表明，DSF与正常组织和肿瘤组织中的细胞锌相互作用，形成DSF-锌复合体m，这在两种组织切片中都能观察到。

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.