The risk of developing normal tissue injuries often limits the radiation dose that can be applied to the
tumour in radiation therapy. Microbeam Radiation Therapy (MRT), a spatially fractionated photon
radiotherapy is currently tested at the European Synchrotron Radiation Facility (ESRF) to improve normal
tissue protection. MRT utilizes an array of microscopically thin and nearly parallel X-ray beams that are
generated by a synchrotron. At the ion microprobe SNAKE in Munich focused proton microbeams
(“proton microchannels”) are studied to improve normal tissue protection. Here, we comparatively
investigate microbeam/microchannel irradiations with sub-millimetre X-ray versus proton beams to
minimize the risk of normal tissue damage in a human skin model, in vitro. Skin tissues were irradiated
with a mean dose of 2 Gy over the irradiated area either with parallel synchrotron-generated X-ray
beams at the ESRF or with 20 MeV protons at SNAKE using four different irradiation modes: homogeneous
field, parallel lines and microchannel applications using two different channel sizes. Normal tissue
viability as determined in an MTT test was significantly higher after proton or X-ray microchannel
irradiation compared to a homogeneous field irradiation. In line with these findings genetic damage, as
determined by the measurement of micronuclei in keratinocytes, was significantly reduced after proton
or X-ray microchannel compared to a homogeneous field irradiation. Our data show that skin irradiation
using either X-ray or proton microchannels maintain a higher cell viability and DNA integrity compared
to a homogeneous irradiation, and thus might improve normal tissue protection after radiation therapy