Tumor Cell Response to Synchrotron Microbeam Radiation Therapy Differs Markedly From Cells in Normal Tissues

Jeffrey C. Crosbie, Robin L. Anderson, Kai Rothkamm, Christina M. Restall, Leonie Cann, Saleela Ruwanpura, Sarah Meachem, Naoto Yagi, Imants Svalbe, Robert A. Lewis, Bryan R.G. Williams, Peter A.W. Rogers*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

111 Citations (Scopus)

Abstract

Purpose: High-dose synchrotron microbeam radiation therapy (MRT) can be effective at destroying tumors in animal models while causing very little damage to normal tissues. The aim of this study was to investigate the cellular processes behind this observation of potential clinical importance. Methods and Materials: MRT was performed using a lattice of 25 μm-wide, planar, polychromatic, kilovoltage X-ray microbeams, with 200-μm peak separation. Inoculated EMT-6.5 tumor and normal mouse skin tissues were harvested at defined intervals post-MRT. Immunohistochemical detection of γ-H2AX allowed precise localization of irradiated cells, which were also assessed for proliferation and apoptosis. Results: MRT significantly reduced tumor cell proliferation by 24 h post-irradiation (p = 0.002). An unexpected finding was that within 24 h of MRT, peak and valley irradiated zones were indistinguishable in tumors because of extensive cell migration between the zones. This was not seen in MRT-treated normal skin, which appeared to undergo a coordinated repair response. MRT elicited an increase in median survival times of EMT-6.5 and 67NR tumor-inoculated mice similar to that achieved with conventional radiotherapy, while causing markedly less normal tissue damage. Conclusions: This study provides evidence of a differential response at a cellular level between normal and tumor tissues after synchrotron MRT.

Original languageEnglish
Pages (from-to)886-894
Number of pages9
JournalInternational Journal of Radiation Oncology Biology Physics
Volume77
Issue number3
DOIs
Publication statusPublished - 2010

Bibliographical note

Funding Information:
Supported by a Cancer Council Victoria Venture Grant (to P.A.W.R., R.A.L., I.S., and B.W.); an Australian Nuclear Science and Technology Organisation (ANSTO) grant (to J.C.C. and P.A.W.R.); a Monash University postgraduate scholarship (to J.C.C.); a National Breast Cancer Foundation Fellowship (to R.L.A.); a Cancer Research UK grant ( C14504/A6116 ; to K.R.); and a National Health and Medical Research Council of Australia Fellowship (Grant No. 143805 ; to P.A.W.R.).

Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.

Keywords

  • Cellular response
  • EMT-6
  • Gamma-H2AX
  • Microbeam radiation therapy
  • Synchrotron

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