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JBIC Journal of Biological Inorganic Chemistry

, Volume 10, Issue 5, pp 443–452 | Cite as

Intracellular mapping of the distribution of metals derived from the antitumor metallocenes

  • Jenny B. Waern
  • Hugh H. Harris
  • Barry Lai
  • Zhonghou Cai
  • Margaret M. HardingEmail author
  • Carolyn T. Dillon
Original Article

Abstract

The intracellular distribution of transition metals in V79 Chinese hamster lung cells treated with subtoxic doses of the organometallic anticancer complexes Cp2MCl2, where Cp is η5 -cyclopentadienyl and M is Mo, Nb, Ti, or V, has been studied by synchrotron-based X-ray fluorescence (XRF). While significantly higher concentrations of Mo and Nb were found in treated cells compared with control cells, distinct differences in the cellular distribution of each metal were observed. Analysis of thin sections of cells was consistent with some localization of Mo in the nucleus. Studies with a noncytotoxic thiol derivative of molybdocene dichloride showed an uneven distribution of Mo in the cells. For comparison, the low levels of Ti and V in cells treated with the more toxic titanocene and vanadocene complexes, respectively, resulted in metal concentrations at the detection limit of XRF. The results agree with independent chemical studies that have concluded that the biological chemistry of each of the metallocene dihalides is unique.

Keywords

Molybdocene dichloride Niobocene dichloride X-ray fluorescence Cellular distribution Synchrotron-radiation-induced X-ray emission 

Abbreviations

AAS

Atomic absorption spectroscopy

Cp

η5-Cyclopentadienyl

EAT

Erhlich ascites tumor

GFAAS

Graphite furnace atomic absorption spectroscopy

ICP

Inductively coupled plasma

PBS

Phosphate-buffered saline

SRIXE

Synchrotron-radiation-induced X-ray emission

XRF

X-ray fluorescence

Notes

Acknowledgements

This work was supported by the Sydney University Cancer Research Fund and the Australian Synchrotron Research Program, which is funded by the Commonwealth of Australia under the Major National Research Facilities program. The use of APS facilities was supported by the US Department of Energy, Basic Energy Sciences, Office of Science, under contract no. W-31-109-Eng-38. J.B.W. gratefully acknowledges the receipt of an Australian Postgraduate Award. H.H.H. acknowledges support from an Australian Synchrotron Research Program Postdoctoral Fellowship.

Supplementary material

775_2005_649_MOESM1_ESM.pdf (1 mb)
(PDF 1 MB)

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Copyright information

© SBIC 2005

Authors and Affiliations

  • Jenny B. Waern
    • 1
  • Hugh H. Harris
    • 1
  • Barry Lai
    • 3
  • Zhonghou Cai
    • 3
  • Margaret M. Harding
    • 1
    Email author
  • Carolyn T. Dillon
    • 2
  1. 1.School of ChemistryThe University of SydneySydneyAustralia
  2. 2.Department of ChemistryUniversity of WollongongWollongongAustralia
  3. 3.Experimental Facilities DivisionArgonne National LaboratoryArgonneUSA

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