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

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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.