The Effectiveness of 20 MeV Protons at Nanosecond Pulse Lengths in Producing Chromosome Aberrations in Human-Hamster Hybrid Cells

The radiobiology of laser-driven particle beams: focus on sub-lethal responses of normal human cells

“…In fact, the majority of in vitro studies making use of different sources confirm that in the therapeutically relevant dose range of a few Gy, even if applied in a single pulse of only few nanoseconds duration, non-linear radiobiological effects due to simultaneous multiple damages in cells and, thus, below any timescale of repair mechanisms, are unlikely to arise [30][31][32][33][34][35]. Only two relevant exceptions exist: Achayra et al [36], who reported a decrease in genetic damage measured as micronucleus formation after a single pulse of electrons but not after multiple pulses (10 6 to 10 8 Gy/s), hypothesising more efficient radical recombination; Schmid et al [37], who found a slight decrease in effectiveness at causing (some types of) chromosome aberrations after nanopulsed protons (conventionally accelerated). Of fundamental importance to gain insights into laser-driven particle biological effectiveness is, of course, in vivo work.…”

The Effects of Ultra-High Dose Rate Proton Irradiation on Growth Delay in the Treatment of Human Tumor Xenografts in Nude Mice

“…These data are of high relevance for clinical use of laser-accelerated proton beams. Previous experiments on monolayer and 3D tissue cultures (in vitro) did not provide evidence for significantly altered radiobiological effectiveness in terms of cytogenetic damage or DNA repair (8)(9)(10)(11)(12). The RBE values determined for pulsed and continuous irradiation modes were always comparable to the RBE of 1.1, which is achieved by conventional proton therapy (20).…”

“…However, based on our previous in vitro experiments (8)(9)(10)(11)(12) we do not expect a relevant difference between pulsed and conventional proton irradiation.…”

“…With respect to these endpoints no indication for a significantly altered efficiency of pulsed protons compared to a continuous irradiation was observed (8)(9)(10)(11). Further biological experiments were performed using a human skin tissue model to account for the 3D geometry and the cell interaction, again without statistically significant changes in RBE according to dose rate (12).…”

Chromosome aberrations and cellular premature senescence as radiation-induced sub-lethal effects: Implications for laser-driven charged-particle radiotherapy

“…Very little is known as to the possible influence that very high dose rates or the pulsed time-structure in dose delivery may have on such late effects in the case of laser-driven charged particle beams. For example, Schmid et al [27] reported that 20 MeV protons in pulsed mode were slightly less effective at inducing CA in human-hamster hybrid cells as compared to this beam being delivered in conventional continuous fashion. However, no information was given on the complexity spectrum of such CAs as the latter were scored only with basic solid staining rather than by FISH.…”