Ultra-short laser-accelerated proton pulses have similar DNA-damaging effectiveness but produce less immediate nitroxidative stress than conventional proton beams

Ultra-short proton pulses originating from laser-plasma accelerators can provide instantaneous dose rates at least 10⁷-fold in excess of conventional, continuous proton beams. The impact of such extremely high proton dose rates on A549 human lung cancer cells was compared with conventionally accelerated protons and 90 keV X-rays. Between 0.2 and 2 Gy, the yield of DNA double strand breaks (foci of phosphorylated histone H2AX) was not significantly different between the two proton sources or proton irradiation and X-rays. Protein nitroxidation after 1 h judged by 3-nitrotyrosine generation was 2.5 and 5-fold higher in response to conventionally accelerated protons compared to laser-driven protons and X-rays, respectively. This difference was significant (p < 0.01) between 0.25 and 1 Gy. In conclusion, ultra-short proton pulses originating from laser-plasma accelerators have a similar DNA damaging potential as conventional proton beams, while inducing less immediate nitroxidative stress, which probably entails a distinct therapeutic potential.