Tumor cell response to synchrotron microbeam radiation therapy differs markedly from cells in normal tissues.
OBJECTIVE
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
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.
School of Physics, Monash University, Clayton, Victoria, Australia.
Jeffrey C
JC
Crosbie
Robin L
RL
Anderson
Kai
K
Rothkamm
Christina M
CM
Restall
Leonie
L
Cann
Saleela
S
Ruwanpura
Sarah
S
Meachem
Naoto
N
Yagi
Imants
I
Svalbe
Robert A
RA
Lewis
Bryan R G
BR
Williams
Peter A W
PA
Rogers
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015415:Biomarkers / Q000032:analysis; D002465:Cell Movement / Q000502:physiology / Q000528:radiation effects; D049109:Cell Proliferation / Q000528:radiation effects; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair / Q000502:physiology; D005260:Female; D006657:Histones / Q000032:analysis*; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D011833:Radiation Injuries, Experimental / Q000378:metabolism / Q000517:prevention & control*; D011836:Radiation Tolerance / Q000235:genetics / Q000502:physiology*; D011897:Random Allocation; D012867:Skin / Q000166:cytology / Q000528:radiation effects*; D017356:Synchrotrons; D013997:Time Factors
D015415:Biomarkers; D006657:Histones; C475961:gamma-H2AX protein, mouse