title: Element array by scanning X-ray fluorescence microscopy after cis-diamminedichloro-platinum(II) treatment.
abstract: 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.
authors.affiliation: Department of Intractable Diseases, International Medical Center of Japan, Tokyo.
authors.forename: Mari
authors.initials: M
authors.lastname: Shimura
authors.forename: Akira
authors.initials: A
authors.lastname: Saito
authors.forename: Satoshi
authors.initials: S
authors.lastname: Matsuyama
authors.forename: Takahiro
authors.initials: T
authors.lastname: Sakuma
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Terui
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Ueno
authors.forename: Hirokatsu
authors.initials: H
authors.lastname: Yumoto
authors.forename: Kazuto
authors.initials: K
authors.lastname: Yamauchi
authors.forename: Kazuya
authors.initials: K
authors.lastname: Yamamura
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Mimura
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Sano
authors.forename: Makina
authors.initials: M
authors.lastname: Yabashi
authors.forename: Kenji
authors.initials: K
authors.lastname: Tamasaku
authors.forename: Kazuto
authors.initials: K
authors.lastname: Nishio
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Nishino
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Endo
authors.forename: Kiyohiko
authors.initials: K
authors.lastname: Hatake
authors.forename: Yuzo
authors.initials: Y
authors.lastname: Mori
authors.forename: Yukihito
authors.initials: Y
authors.lastname: Ishizaka
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ishikawa
mesh_terms: D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000494:pharmacology; D002945:Cisplatin / Q000493:pharmacokinetics / Q000494:pharmacology*; D004347:Drug Interactions; D019008:Drug Resistance, Neoplasm; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008658:Inactivation, Metabolic; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D008668:Metallothionein / Q000378:metabolism; D008856:Microscopy, Fluorescence / Q000379:methods; D010984:Platinum / Q000493:pharmacokinetics; D013052:Spectrometry, X-Ray Emission / Q000379:methods; D015032:Zinc / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D002614:Chelating Agents; D010984:Platinum; D008668:Metallothionein; D005978:Glutathione; D015032:Zinc; D002945:Cisplatin