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.

Purpose: Radiotherapy for head and neck cancer may result in serious side effects, such as hyposalivation, impairing the patient's quality of life. Modern radiotherapy techniques attempt to reduce the dose to salivary glands, which, however, results in low-dose irradiation of the tissue stem cells. Here we assess the low-dose sensitivity of tissue stem cells and the consequences for tissue function. Experimental Design: Postirradiation rat salivary gland secretory function was determined after pilocarpine induction. Murine and patient-derived salivary gland and thyroid gland organoids were irradiated and clonogenic survival was assessed. The DNA damage response (DDR) was analyzed in organoids and modulated using different radiation modalities, chemical inhibition, and genetic modification. Results: Relative low-dose irradiation to the high-density stem cell region of rat salivary gland disproportionally impaired function. Hyper-radiosensitivity at doses <1 Gy, followed by relative radioresistance at doses ≥1 Gy, was observed in salivary gland and thyroid gland organoid cultures. DDR modulation resulted in diminished, or even abrogated, relative radioresistance. Furthermore, inhibition of the DDR protein ATM impaired DNA repair after 1 Gy, but not 0.25 Gy. Irradiation of patient-derived salivary gland organoid cells showed similar responses, whereas a single 1 Gy dose to salivary gland–derived stem cells resulted in greater survival than clinically relevant fractionated doses of 4 × 0.25 Gy. Conclusions: We show that murine and human glandular tissue stem cells exhibit a dose threshold in DDR activation, resulting in low-dose hyper-radiosensitivity, with clinical implications in radiotherapy treatment planning. Furthermore, our results from patient-derived organoids highlight the potential of organoids to study normal tissue responses to radiation.

EPJ Web of Conferences, open-access proceedings in physics and astronomy

Purpose: The purpose of this work is the three‐dimensional characterization of the active volumes of commercial solid‐state dosimetry detectors. Detailed knowledge of the dimensions of the detector’s active volume as well as the detector housing is of particular interest for small‐field photon dosimetry. As shown in previous publications from different groups, the design of the detector housing influences the detector signal for small photon fields. Therefore, detailed knowledge of the active volume dimension and the surrounding materials form the basis for accurate Monte Carlo simulations of the detector.Methods: A 10 MeV proton beam focused by the microbeam system of the Physikalisch‐Technische Bundesanstalt was used to measure two‐dimensional response maps of a synthetic diamond detector (microDiamond, type 60019, PTW Freiburg) and two silicon detectors (microSilicon, type 60023, PTW Freiburg and Diode E, type 60017, PTW Freiburg). In addition, the thickness of the active volume of the new microSilicon was measured using the method developed in a previous study.Results: The analysis of the response maps leads to active area of 1.18 mm² for the Diode E, 1.75 mm² for the microSilicon, and 3.91 mm² for the microDiamond detector. The thickness of the active volume of the microSilicon detector was determined to be (17.8 ± 2) µm.Conclusions: This study provides detailed geometrical data of the dosimetric active volume of three different solid‐state detector types.

Advances in accelerator technology, which have enabled conforming radiotherapy with charged hadronic species, have brought benefits as well as potential new risks to patients. To better understand the effects of ionizing radiation on tumor and surrounding tissue, it is important to investigate and quantify the relationship between energy deposition at the nanometric scale and the initial biological events. Monte Carlo track structure simulation codes provide a powerful tool for investigating this relationship; however, their success and reliability are dependent on their improvement and development accordingly to the dedicated biological data to which they are challenged. For this aim, a microbeam facility that allows for fluence control, down to one ion per cell nucleus, was used to evaluate relative frequencies of DNA damage after interaction between the incoming ion and DNA according to radiation quality. Primary human cells were exposed to alpha particles of three different energies with respective li...