20.500.12556/DiRROS-19277 Pulsed low dose-rate irradiation response in isogenic HNSCC cell lines with different radiosensitivity . Management of locoregionally recurrent head and neck squamous cell carcinomas (HNSCC) is challenging due to potential radioresistance. Pulsed low-dose rate (PLDR) irradiation exploits phenomena of increased radiosensitivity, low-dose hyperradiosensitivity (LDHRS), and inverse dose-rate effect. The purpose of this study was to evaluate LDHRS and the effect of PLDR irradiation in isogenic HNSCC cells with different radiosensitivity. Materials and methods. Cell survival after different irradiation regimens in isogenic parental FaDu and radioresistant FaDu-RR cells was determined by clonogenic assay; post irradiation cell cycle distribution was studied by flow cytometry; the expression of DNA damage signalling genes was assesed by reverse transcription-quantitative PCR. Results. Radioresistant Fadu-RR cells displayed LDHRS and were more sensitive to PLDR irradiation than parental FaDu cells. In both cell lines, cell cycle was arrested in G2/M phase 5 hours after irradiation. It was restored 24 hours after irradiation in parental, but not in the radioresistant cells, which were arrested in G1-phase. DNA damage signalling genes were under-expressed in radioresistant compared to parental cells. Irradiation increased DNA damage signalling gene expression in radioresistant cells, while in parental cells only few genes were under-expressed. Conclusions. We demonstrated LDHRS in isogenic radioresistant cells, but not in the parental cells. Survival of LDHRSpositive radioresistant cells after PLDR was significantly reduced. This reduction in cell survival is associated with variations in DNA damage signalling gene expression observed in response to PLDR most likely through different regulation of cell cycle checkpoints. DNA damage isogenic cell lines low dose irradiation pulsed low dose-rate irradiation radiosensitivity true false true Association of Radiology and Oncology Ljubljana Angleški jezik Slovenski jezik by Authors Neznano 2024-07-12 10:26:23 2024-07-12 10:26:23 2024-07-13 03:49:23 0000-00-00 00:00:00 2020 0 0 str. 168-179, IV no. 2 Vol. 54 2020 0000-00-00 Zaloznikova Objavljeno apc 0000-00-00 0000-00-00 2020-01-01 602.6/.7 1318-2099 10.2478/raon-2020-0015 3520379 RAZ_Todorovic_Vesna_2020.pdf RAZ_Todorovic_Vesna_2020.pdf 1 61DE6B99DC0CC65D6E8FA69BF05362FA 8050056166ba412286c8be6ad6e052ac088c221c6d3fba58fdfcd54b54013441 9ed67ada-4028-11ef-b487-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=26560 Onkološki inštitut Ljubljana 0 0 0