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. 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.