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| Home > Publications database > ROS generation and cellular response under irradiation with the FLASHLAB@PITZ electron beam at ultra-high and low dose rates |
| Conference Presentation | PUBDB-2024-07516 |
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2024
Abstract: Background and Aims: R&D platform FLASHlab@PITZ (Photo Injector Test facility at DESY in Zeuthen) collaborates with Technical University of Applied Sciences Wildau to provide radiation oncology community with an in vitro and in vivo infrastructure for systematic investigation of electron irradiation at an extremely wide dose rates from conventional (CONV) up to 1014 Gy/s. The initial biochemical in vitro effects of the irradiation at FLASHlab@PITZ will be presented in this contribution.Methods: Irradiation was performed at startup FLASH-beamline using an 18 MeV PITZ electron beam with doses ≤150Gy and dose rates of 0.05Gy/s and 1.5-3.3x105Gy/s (UHDR). Hydrogen peroxide (H2O2) production was estimated with AmplexRed at 4 and 1% O2. Survival, prooxidant and proapoptotic effects in human lung carcinoma A549 and fibroblast HEL299 cells at 21% O2were evaluated using clonogenic, 2’,7’-Dichlorfluoreszeindiacetat and Caspase-Glo®3/7 assays, respectively. X-ray irradiation of cells was done at 0.015Gy/s with the 200keV X-ray generator Comet-Yxlon-Maxishot.Results: H2O2 generation was hindered with [O2] drop, while the lower H2O2 yield at UHDR compared to CONV was consistent along all investigated [O2]. Decreased A549 and HEL299 cell survival was similar for CONV and UHDR electron irradiation, following the effects of CONV Xray irradiation. The intracellular ROS generation was 6-folds higher after CONV irradiation of HEL299 cells as compared to UHDR. HEL299 cells were characterized with gradual increase of the caspase 3/7 activity to 159±5% after CONV with electron and X-rays, while no change was detected after UHDR electron irradiation.Conclusions: CONV irradiation had prooxidant and proapoptotic effect on HEL299, but not on A549 cells. The increase of dose rate to UHDR negated those effects, that pointed on its sparing capability. However, CONV and UHDR irradiation had similar effect on both cell survival, evidencing complex pattern of cellular response and highlighting a need of in vivo studies. FLASHlab@PITZ animal laboratory is in the final preparation phase.
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