Tumor cell response to synchrotron microbeam radiation therapy differs markedly from cells in normal tissues
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Tumor cell response to synchrotron microbeam radiation therapy differs markedly from cells in normal tissues. / Crosbie, Jeffrey C; Anderson, Robin L; Rothkamm, Kai; Restall, Christina M; Cann, Leonie; Ruwanpura, Saleela; Meachem, Sarah; Yagi, Naoto; Svalbe, Imants; Lewis, Robert A; Williams, Bryan R G; Rogers, Peter A W.
In: INT J RADIAT ONCOL, Vol. 77, No. 3, 01.07.2010, p. 886-94.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Tumor cell response to synchrotron microbeam radiation therapy differs markedly from cells in normal tissues
AU - Crosbie, Jeffrey C
AU - Anderson, Robin L
AU - Rothkamm, Kai
AU - Restall, Christina M
AU - Cann, Leonie
AU - Ruwanpura, Saleela
AU - Meachem, Sarah
AU - Yagi, Naoto
AU - Svalbe, Imants
AU - Lewis, Robert A
AU - Williams, Bryan R G
AU - Rogers, Peter A W
N1 - (c) 2010 Elsevier Inc. All rights reserved.
PY - 2010/7/1
Y1 - 2010/7/1
N2 - 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 mum-wide, planar, polychromatic, kilovoltage X-ray microbeams, with 200-microm peak separation. Inoculated EMT-6.5 tumor and normal mouse skin tissues were harvested at defined intervals post-MRT. Immunohistochemical detection of gamma-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.
AB - 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 mum-wide, planar, polychromatic, kilovoltage X-ray microbeams, with 200-microm peak separation. Inoculated EMT-6.5 tumor and normal mouse skin tissues were harvested at defined intervals post-MRT. Immunohistochemical detection of gamma-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.
KW - Animals
KW - Apoptosis/physiology
KW - Biomarkers/analysis
KW - Cell Movement/physiology
KW - Cell Proliferation/radiation effects
KW - DNA Breaks, Double-Stranded
KW - DNA Repair/physiology
KW - Female
KW - Histones/analysis
KW - Mammary Neoplasms, Experimental/genetics
KW - Mice
KW - Mice, Inbred BALB C
KW - Radiation Injuries, Experimental/metabolism
KW - Radiation Tolerance/genetics
KW - Random Allocation
KW - Skin/cytology
KW - Synchrotrons
KW - Time Factors
U2 - 10.1016/j.ijrobp.2010.01.035
DO - 10.1016/j.ijrobp.2010.01.035
M3 - SCORING: Journal article
C2 - 20510199
VL - 77
SP - 886
EP - 894
JO - INT J RADIAT ONCOL
JF - INT J RADIAT ONCOL
SN - 0360-3016
IS - 3
ER -