Currently, all soft tissue sarcomas (STS) are irradiated by the same regimen, disregarding possible subtype-specific radiosensitivities. To gain further insight, cellular radiosensitivity was... Show moreCurrently, all soft tissue sarcomas (STS) are irradiated by the same regimen, disregarding possible subtype-specific radiosensitivities. To gain further insight, cellular radiosensitivity was investigated in a panel of sarcoma cell lines. Fourteen sarcoma cell lines, derived from synovial sarcoma, leiomyosarcoma, fibrosarcoma and liposarcoma origin, were submitted to clonogenic survival assays. Cells were irradiated with single doses from 1-8 Gy and surviving fraction (SF) was calculated from the resulting response data. Alpha/beta (alpha/beta) ratios were inferred from radiation-response curves using the linear-quadratic (LQ)-model. Cellular radiosensitivities varied largely in this panel, indicating a considerable degree of heterogeneity. Surviving fraction after 2 Gy (SF2) ranged from 0.27 to 0.76 with evidence of a particular radiosensitive phenotype in only few cell lines. D-37% on the mean data was 3.4 Gy and the median SF2 was 0.52. The median alpha/beta was 4.9 Gy and in six cell lines the alpha/beta was below 4 Gy. A fairly homogeneous radiation response was observed in myxoid liposarcoma cell lines with SF2 between 0.64 and 0.67. Further comparing sarcomas of different origin, synovial sarcomas, as a group, showed the lowest SF2 values (mean 0.35) and was significantly more radiosensitive than myxoid liposarcomas and leiomyosarcomas (P = 0.0084 and 0.024, respectively). This study demonstrates a broad spectrum of radiosensitivities across STS cell lines and reveals subtype-specific radiation responses. The particular cellular radiasensitivity of synovial sarcoma cells supports consideration of the different sarcoma entities in clinical studies that aim to optimize sarcoma radiotherapy. (C) 2021 by Radiation Research Society Show less
Boei, J.J.W.A.; Vermeulen, S.; Skubakova, M.M.; Meijers, M.; Loenen, W.A.M.; Wolterbeek, R.; ... ; Giphart-Gassler, M. 2012
Abstract Cockayne syndrome (CS) cells are defective in transcription-coupled repair (TCR) and sensitive to oxidizing agents, including ionizing radiation. We examined the hypothesis that TCR plays... Show moreAbstract Cockayne syndrome (CS) cells are defective in transcription-coupled repair (TCR) and sensitive to oxidizing agents, including ionizing radiation. We examined the hypothesis that TCR plays a role in ionizing radiation-induced oxidative DNA damage repair or alternatively that CS plays a role in transcription elongation after irradiation. Irradiation with doses up to 100?Gy did not inhibit RNA polymerase II-dependent transcription in normal and CS-B fibroblasts. In contrast, RNA polymerase I-dependent transcription was severely inhibited at 5?Gy in normal cells, indicating different mechanisms of transcription response to X rays. The frequency of radiation-induced base damage was 2 ? 10(?7) lesions/base/Gy, implying that 150?Gy is required to induce one lesion/30-kb transcription unit; no TCR of X-ray-induced base damage in the p53 gene was observed. Therefore, it is highly unlikely that defective TCR underlies the sensitivity of CS to ionizing radiation. Overall genome repair levels of radiation-induced DNA damage measured by repair replication were significantly reduced in CS-A and CS-B cells. Taken together, the results do not provide evidence for a key role of TCR in repair of radiation-induced oxidative damages in human cells; rather, impaired repair of oxidative lesions throughout the genome may contribute to the CS phenotype. Show less
