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Element Array by Scanning X-ray Fluorescence Microscopy after Cis-Diamminedichloro-Platinum(II) Treatment

¹ Department of Intractable Diseases, International Medical Center of Japan; ² Pharmacology Division, National Cancer Center Research Institute; ³ Division of Clinical Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo, Japan; Departments of ⁴ Material and Life Science and ⁵ Precision Science and Technology, and ⁶ Research Center for Ultra-Precision Science and Technology, Graduate School of Engineering, Osaka University, Suita, Osaka, Japan; ⁷ SPring-8/Japan Synchrotron Radiation Research Institute and ⁸ SPring-8/Riken, Hyogo, Japan; and ⁹ Nanoscale Quantum Conductor Array Project, ICORP, Saitama, Japan

Requests for reprints: Yukihito Ishizaka, Department of Intractable Diseases, International Medical Center of Japan, 1-21-1 Toyama, Shinjuku-ku, 162-8655 Tokyo, Japan. Phone/Fax: 81-3-5272-7527; E-mail: zakay{at}ri.imcj.go.jp.

Minerals are important for cellular functions, such as transcription and enzyme activity, and are also involved in the metabolism of anticancer chemotherapeutic compounds. Profiling of intracellular elements in individual cells could help in understanding the mechanism of drug resistance in tumors and possibly provide a new strategy of anticancer chemotherapy. Using a recently developed technique of scanning X-ray fluorescence microscopy (SXFM), we analyzed intracellular elements after treatment with cis-diamminedichloro-platinum(II) (CDDP), a platinum-based anticancer agent. The images obtained by SXFM (element array) revealed that the average Pt content of CDDP-resistant cells was 2.6 times less than that of sensitive cells, and the zinc content was inversely correlated with the intracellular Pt content. Data suggested that Zn-related detoxification is responsible for resistance to CDDP. Of Zn-related excretion factors, glutathione was highly correlated with the amount of Zn. The combined treatment of CDDP and a Zn(II) chelator resulted in the incorporation of thrice more Pt with the concomitant down-regulation of glutathione. We propose that the generation of an element array by SXFM opens up new avenues in cancer biology and treatment.