@article{MTMT:33757973, title = {RENEB Inter-Laboratory Comparison 2021: The Dicentric Chromosome Assay}, url = {https://m2.mtmt.hu/api/publication/33757973}, author = {Endesfelder, D. and Oestreicher, U. and Bucher, M. and Beinke, C. and Siebenwirth, C. and Ainsbury, E. and Moquet, J. and Gruel, G. and Gregoire, E. and Martinez, J.S. and Vral, A. and Baeyens, A. and Valente, M. and Montoro, A. and Terzoudi, G. and Triantopoulou, S. and Pantelias, A. and Gil, O. Monteiro and Prieto, M.J. and Domene, M.M. and Zafiropoulos, D. and Barquinero, J.F. and Pujol-Canadell, M. and Lumniczky, Katalin and Hargitai, Rita and Kis, Enikő and Testa, A. and Patrono, C. and Sommer, S. and Hristova, R. and Kostova, N. and Atanasova, M. and Sevriukova, O. and Domínguez, I. and Pastor, N. and Güçlü, I. and Pajic, J. and Sabatier, L. and Brochard, P. and Tichy, A. and Milanova, M. and Finot, F. and Petrenci, C. Cuceu and Wilkins, R.C. and Beaton-Green, L.A. and Seong, K.M. and Lee, Y. and Lee, Y.H. and Balajee, A.S. and Maznyk, N. and Sypko, T. and Pham, N.D. and Tran, T.M. and Miura, T. and Suto, Y. and Akiyamam, M. and Tsuyama, N. and Abe, Y. and Goh, V.S.T. and Chua, C.E.L. and Abend, M. and Port, M.}, doi = {10.1667/RADE-22-00202.1}, journal-iso = {RADIAT RES}, journal = {RADIATION RESEARCH}, volume = {199}, unique-id = {33757973}, issn = {0033-7587}, abstract = {After large-scale radiation accidents where many individuals are suspected to be exposed to ionizing radiation, biological and physical retrospective dosimetry assays are important tools to aid clinical decision making by categorizing individuals into unexposed/minimally, moderately or highly exposed groups. Quality-controlled inter-laboratory comparisons of simulated accident scenarios are regularly performed in the frame of the European legal association RENEB (Running the European Network of Biological and Physical retrospective Dosimetry) to optimize international networking and emergency readiness in case of large-scale radiation events. In total 33 laboratories from 22 countries around the world participated in the current RENEB inter-laboratory comparison 2021 for the dicentric chromosome assay. Blood was irradiated in vitro with X rays (240 kVp, 13 mA, ∼75 keV, 1 Gy/min) to simulate an acute, homogeneous whole-body exposure. Three blood samples (no. 1: 0 Gy, no. 2: 1.2 Gy, no. 3: 3.5 Gy) were sent to each participant and the task was to culture samples, to prepare slides and to assess radiation doses based on the observed dicentric yields from 50 manually or 150 semi-automatically scored metaphases (triage mode scoring). Approximately two-thirds of the participants applied calibration curves from irradiations with γ rays and about 1/3 from irradiations with X rays with varying energies. The categorization of the samples in clinically relevant groups corresponding to individuals that were unexposed/minimally (0–1 Gy), moderately (1–2 Gy) or highly exposed (>2 Gy) was successfully performed by all participants for sample no. 1 and no. 3 and by ≥74% for sample no. 2. However, while most participants estimated a dose of exactly 0 Gy for the sham-irradiated sample, the precise dose estimates of the samples irradiated with doses >0 Gy were systematically higher than the corresponding reference doses and showed a median deviation of 0.5 Gy (sample no. 2) and 0.95 Gy (sample no. 3) for manual scoring. By converting doses estimated based on γ-ray calibration curves to X-ray doses of a comparable mean photon energy as used in this exercise, the median deviation decreased to 0.27 Gy (sample no. 2) and 0.6 Gy (sample no. 3). The main aim of biological dosimetry in the case of a large-scale event is the categorization of individuals into clinically relevant groups, to aid clinical decision making. This task was successfully performed by all participants for the 0 Gy and 3.5 Gy samples and by 74% (manual scoring) and 80% (semi-automatic scoring) for the 1.2 Gy sample. Due to the accuracy of the dicentric chromosome assay and the high number of participating laboratories, a systematic shift of the dose estimates could be revealed. Differences in radiation quality (X ray vs. γ ray) between the test samples and the applied dose effect curves can partly explain the systematic shift. There might be several additional reasons for the observed bias (e.g., donor effects, transport, experimental conditions or the irradiation setup) and the analysis of these reasons provides great opportunities for future research. The participation of laboratories from countries around the world gave the opportunity to compare the results on an international level.}, year = {2023}, eissn = {1938-5404}, pages = {556-570} } @article{MTMT:33757972, title = {RENEB Inter-Laboratory Comparison 2021: The Gamma-H2AX Foci Assay}, url = {https://m2.mtmt.hu/api/publication/33757972}, author = {Moquet, Jayne and Ainsburym, Elizabeth and Balázs, Katalin and Barnard, Stephen and Hristova, Rositsa and Lumniczky, Katalin and Port, Matthias and Roessler, Ute and Scherthan, Harry and Staynova, Albena and Szatmári, Tünde and Wojewodzka, Maria and Abend, Michael}, doi = {10.1667/RADE-22-00205.1}, journal-iso = {RADIAT RES}, journal = {RADIATION RESEARCH}, volume = {199}, unique-id = {33757972}, issn = {0033-7587}, abstract = {The Running the European Network of biological and retrospective dosimetry (RENEB) network of laboratories has a range of biological and physical dosimetry assays that can be deployed in the event of a radiation incident to provide exposure assessment. To maintain operational capability and provide training, RENEB runs regular inter-laboratory comparison (ILC) exercises. The RENEB ILC2021 was carried out with all the biological and physical dosimetry assays employed in the network. The focus of this paper is to evaluate the results from 6 laboratories that took part using the gamma-H2AX radiation-induced foci assay. For two laboratories this was their first RENEB ILC. Blood samples were homogenously exposed to 240 kVp X rays (1 Gy/min) to provide calibration data, (0–4 Gy), and a few weeks later three blind coded test samples, (0, 1.2 and 3.5 Gy) were prepared. All samples were allowed a 2 h repair time at 37°C before being transported, on ice packs, to the participating laboratories. On arrival, the samples were processed, scored either manually or automatically for gamma-H2AX foci and dose estimates for the 3 blind coded samples sent to the organizing laboratory. The temperature of samples during transit and the time taken to report the dose estimates were recorded. Subsequent examination of the data from each laboratory used the doses estimates to assign triage categories to the samples. After receipt of the samples, the quickest report of dose estimates was 4.6 h. Analysis of variance revealed that the laboratory carrying out the assay had a significant effect on the foci yield (P < 0.001) for the calibration data, but not on the dose estimates of the blind coded samples (P = 0.101). All laboratories correctly identified the unirradiated and irradiated samples, although the dose estimates for the latter tended to under-estimate the dose. Two participants seriously under-estimated the dose for the highly exposed sample, which resulted in the sample being placed in the lowest triage category not the highest. However, this under-estimation resulted from the samples not remaining cold during shipment, due to a delay in transit and was not related to the experience of the participating laboratory. Overall, the RENEB network laboratories have demonstrated it is possible to quickly identify a recent whole-body acute exposure using the gamma-H2AX assay within the conditions of the ILC. In addition, an ILC provides a useful training and harmonization exercise for laboratories.}, year = {2023}, eissn = {1938-5404}, pages = {591-597}, orcid-numbers = {Szatmári, Tünde/0000-0001-7727-9589} } @article{MTMT:33757969, title = {RENEB Inter-Laboratory Comparison 2021: The Gene Expression Assay}, url = {https://m2.mtmt.hu/api/publication/33757969}, author = {Abend, M. and Amundson, S.A. and Badie, C. and Brzoska, K. and Kriehuber, R. and Lacombe, J. and Lopez-Riego, M. and Lumniczky, Katalin and Endesfelder, D. and O'Brien, G. and Doucha-Senf, S. and Ghandhi, S.A. and Hargitai, Rita and Kis, Enikő and Lundholm, L. and Oskamp, D. and Ostheim, P. and Schüle, S. and Schwanke, D. and Shuryak, I. and Siebenwith, C. and Unverricht-Yeboah, M. and Wojcik, A. and Yang, J. and Zenhausern, F. and Port, M.}, doi = {10.1667/RADE-22-00206.1}, journal-iso = {RADIAT RES}, journal = {RADIATION RESEARCH}, volume = {199}, unique-id = {33757969}, issn = {0033-7587}, abstract = {Early and high-throughput individual dose estimates are essential following large-scale radiation exposure events. In the context of the Running the European Network for Biodosimetry and Physical Dosimetry (RENEB) 2021 exercise, gene expression assays were conducted and their corresponding performance for dose-assessment is presented in this publication. Three blinded, coded whole blood samples from healthy donors were exposed to 0, 1.2 and 3.5 Gy X-ray doses (240 kVp, 1 Gy/min) using the X-ray source Yxlon. These exposures correspond to clinically relevant groups of unexposed, low dose (no severe acute health effects expected) and high dose exposed individuals (requiring early intensive medical health care). Samples were sent to eight teams for dose estimation and identification of clinically relevant groups. For quantitative reverse transcription polymerase chain reaction (qRT-PCR) and microarray analyses, samples were lysed, stored at 20°C and shipped on wet ice. RNA isolations and assays were run in each laboratory according to locally established protocols. The time-to-result for both rough early and more precise later reports has been documented where possible. Accuracy of dose estimates was calculated as the difference between estimated and reference doses for all doses (summed absolute difference, SAD) and by determining the number of correctly reported dose estimates that were defined as ±0.5 Gy for reference doses <2.5 Gy and ±1.0 Gy for reference doses >3 Gy, as recommended for triage dosimetry. We also examined the allocation of dose estimates to clinically/diagnostically relevant exposure groups. Altogether, 105 dose estimates were reported by the eight teams, and the earliest report times on dose categories and estimates were 5 h and 9 h, respectively. The coefficient of variation for 85% of all 436 qRT-PCR measurements did not exceed 10%. One team reported dose estimates that systematically deviated several-fold from reported dose estimates, and these outliers were excluded from further analysis. Teams employing a combination of several genes generated about two-times lower median SADs (0.8 Gy) compared to dose estimates based on single genes only (1.7 Gy). When considering the uncertainty intervals for triage dosimetry, dose estimates of all teams together were correctly reported in 100% of the 0 Gy, 50% of the 1.2 Gy and 50% of the 3.5 Gy exposed samples. The order of dose estimates (from lowest to highest) corresponding to three dose categories (unexposed, low dose and highest exposure) were correctly reported by all teams and all chosen genes or gene combinations. Furthermore, if teams reported no exposure or an exposure >3.5 Gy, it was always correctly allocated to the unexposed and the highly exposed group, while low exposed (1.2 Gy) samples sometimes could not be discriminated from highly (3.5 Gy) exposed samples. All teams used FDXR and 78.1% of correct dose estimates used FDXR as one of the predictors. Still, the accuracy of reported dose estimates based on FDXR differed considerably among teams with one team's SAD (0.5 Gy) being comparable to the dose accuracy employing a combination of genes. Using the workflow of this reference team, we performed additional experiments after the exercise on residual RNA and cDNA sent by six teams to the reference team. All samples were processed similarly with the intention to improve the accuracy of dose estimates when employing the same workflow. Re-evaluated dose estimates improved for half of the samples and worsened for the others. In conclusion, this inter-laboratory comparison exercise enabled (1) identification of technical problems and corrections in preparations for future events, (2) confirmed the early and high-throughput capabilities of gene expression, (3) emphasized different biodosimetry approaches using either only FDXR or a gene combination, (4) indicated some improvements in dose estimation with FDXR when employing a similar methodology, which requires further research for the final conclusion and (5) underlined the applicability of gene expression for identification of unexposed and highly exposed samples, supporting medical management in radiological or nuclear scenarios.}, year = {2023}, eissn = {1938-5404}, pages = {598-615} } @article{MTMT:32576332, title = {Extracellular Vesicles Derived from Bone Marrow in an Early Stage of Ionizing Radiation Damage Are Able to Induce Bystander Responses in the Bone Marrow}, url = {https://m2.mtmt.hu/api/publication/32576332}, author = {Kis, Dávid and Csordás, Barbara and Persa, Eszter and Jezsó, Bálint and Hargitai, Rita and Szatmári, Tünde and Sándor, Nikolett and Kis, Enikő and Balázs, Katalin and Sáfrány, Géza and Lumniczky, Katalin}, doi = {10.3390/cells11010155}, journal-iso = {CELLS-BASEL}, journal = {CELLS}, volume = {11}, unique-id = {32576332}, year = {2022}, eissn = {2073-4409}, orcid-numbers = {Jezsó, Bálint/0000-0002-1306-4797; Szatmári, Tünde/0000-0001-7727-9589; Sáfrány, Géza/0000-0001-9641-8732; Lumniczky, Katalin/0000-0001-8661-1854} } @article{MTMT:32127711, title = {Influence of sample preparation optimization on the accuracy of dose assessment of an automatic non-fluorescent MN scoring system.}, url = {https://m2.mtmt.hu/api/publication/32127711}, author = {Hülber, Tímea Nóra and Kocsis, Zsuzsa and Németh, J and Kis, Enikő and d'Errico, F and Sáfrány, Géza and Pesznyák, Csilla}, doi = {10.1080/09553002.2021.1962573}, journal-iso = {INT J RADIAT BIOL}, journal = {INTERNATIONAL JOURNAL OF RADIATION BIOLOGY}, volume = {97}, unique-id = {32127711}, issn = {0955-3002}, abstract = {Purpose - Automatizing the scoring of the cytokinesis-blocked micronucleus assay spares a lot of valuable time. The dose-effect relationship can be applied reliably for dose estimation, if the quality of the slides is the same from the perspective of the used image processing algorithm. This aspect brings in additional requirements against the quality of the slides compared to the conventional visual scoring.Materials and methods - An add-in software was created to the non-fluorescent RS-MN automatic MN scoring system which is capable of measuring quantitatively the degree of typical anomalies. The image processing is less reliable when the presence of these anomalies is more frequent. The behavior of the designed sample quality parameters (SQPs) was tested on in vitro irradiated peripheral blood samples (0, 1 and 2 Gy) obtained from a healthy donor and also on samples from patients undergoing low dose-rate brachytherapy.Results: We examined 20 different SQPs and identified two that are independent and correlate significantly with the error of the fully automatic MN frequency. One is related to the size of the cells and the other reflects the homogeneity of the environment. An equation was established which presents a connection between the error of the auto MN frequency and the SQPs. By adding a fourth cleaning step to the conventional sample preparation and changing the pre-dripping temperature of the slide, the SQP can be modified and consequently the sample quality can be improved. The gain in accuracy is 54 ± 10 MN per 1000 binucleated cells, which corresponds to the effects of 0.5 Gy. Around the lowest limit of detection (<0.5 Gy) it means a 50-100% drop in error of dose, which is significant. With sample quality harmonization, the positive predictive value was raised to 80 - 93% depending on the dose.Conclusions: With the technique described in this paper, the suitability for automated scoring of a micronucleus slide can be tested quantitatively and objectively. A method is presented with which in some cases the uncertainty of the assessed doses due to variance in sample quality can be decreased or if it is not possible its bias can be predicted. The proposed protocol leads to a more reliable estimation of dose. The SQPs are designed in a way that they have a potential to be adapted to similar systems.}, keywords = {biodosimetry; Automatic micronucleus assay (MN); quantified slide quality; sample preparation optimization}, year = {2021}, eissn = {1362-3095}, pages = {1470-1484}, orcid-numbers = {Hülber, Tímea Nóra/0000-0002-0757-5339; Kocsis, Zsuzsa/0000-0002-4336-3325; Pesznyák, Csilla/0000-0001-5815-0974} } @article{MTMT:32069330, title = {Inter-laboratory comparison of gene expression biodosimetry for protracted radiation exposures as part of the RENEB and EURADOS WG10 2019 exercise}, url = {https://m2.mtmt.hu/api/publication/32069330}, author = {Abend, M. and Amundson, S. A. and Badie, C. and Brzoska, K. and Hargitai, Rita and Kriehuber, R. and Schüle, S. and Kis, Enikő and Ghandhi, S. A. and Lumniczky, Katalin and Morton, S. R. and O’Brien, G. and Oskamp, D. and Ostheim, P. and Siebenwirth, C. and Shuryak, I. and Szatmári, T. and Unverricht-Yeboah, M. and Ainsbury, E. and Bassinet, C. and Kulka, U. and Oestreicher, U. and Ristic, Y. and Trompier, F. and Wojcik, A. and Waldner, L. and Port, M.}, doi = {10.1038/s41598-021-88403-4}, journal-iso = {SCI REP}, journal = {SCIENTIFIC REPORTS}, volume = {11}, unique-id = {32069330}, issn = {2045-2322}, year = {2021}, eissn = {2045-2322} } @article{MTMT:31848670, title = {Oxidative Stress and Gene Expression Modifications Mediated by Extracellular Vesicles: An In Vivo Study of the Radiation-Induced Bystander Effect}, url = {https://m2.mtmt.hu/api/publication/31848670}, author = {Hargitai, Rita and Kis, Dávid and Persa, Eszter and Szatmári, Tünde and Sáfrány, Géza and Lumniczky, Katalin}, doi = {10.3390/antiox10020156}, journal-iso = {ANTIOXIDANTS-BASEL}, journal = {ANTIOXIDANTS}, volume = {10}, unique-id = {31848670}, year = {2021}, eissn = {2076-3921}, orcid-numbers = {Szatmári, Tünde/0000-0001-7727-9589; Sáfrány, Géza/0000-0001-9641-8732} } @article{MTMT:31857479, title = {A CT vizsgálatok mellékhatásai.}, url = {https://m2.mtmt.hu/api/publication/31857479}, author = {Sáfrány, Géza and Lumniczky, Katalin}, journal-iso = {KLINIKAI ONKOLÓGIA}, journal = {KLINIKAI ONKOLÓGIA}, volume = {7}, unique-id = {31857479}, issn = {2064-5058}, year = {2020}, pages = {365-370} } @article{MTMT:31618295, title = {The effect of ionising radiation on the phenotype of bone marrow-derived extracellular vesicles}, url = {https://m2.mtmt.hu/api/publication/31618295}, author = {Kis, Dávid and Persa, Eszter and Szatmári, Tünde and Antal, Lilla and Bóta, Attila and Csordás, Ilona Barbara and Hargitai, Rita and Jezsó, Bálint and Kis, Enikő and Mihály, Judith and Sáfrány, Géza and Varga, Zoltán and Lumniczky, Katalin}, doi = {10.1259/bjr.20200319}, journal-iso = {BRIT J RADIOL}, journal = {BRITISH JOURNAL OF RADIOLOGY}, volume = {93}, unique-id = {31618295}, issn = {0007-1285}, year = {2020}, eissn = {1748-880X}, orcid-numbers = {Szatmári, Tünde/0000-0001-7727-9589; Jezsó, Bálint/0000-0002-1306-4797; Varga, Zoltán/0000-0002-5741-2669} } @article{MTMT:31443468, title = {Systemic modulation of stress and immune parameters in patients treated for prostate adenocarcinoma by intensity-modulated radiation therapy or stereotactic ablative body radiotherapy}, url = {https://m2.mtmt.hu/api/publication/31443468}, author = {Frey, B. and Mika, J. and Jelonek, K. and Cruz-Garcia, L. and Roelants, C. and Testard, I and Cherradi, N. and Lumniczky, Katalin and Polozov, S. and Napieralska, A. and Widlak, P. and Gaipl, U. S. and Badie, C. and Polanska, J. and Candelas, S. M.}, doi = {10.1007/s00066-020-01637-5}, journal-iso = {STRAHLENTHER ONKOL}, journal = {STRAHLENTHERAPIE UND ONKOLOGIE}, volume = {196}, unique-id = {31443468}, issn = {0179-7158}, abstract = {Background In this exploratory study, the impact of local irradiation on systemic changes in stress and immune parameters was investigated in eight patients treated with intensity-modulated radiation therapy (IMRT) or stereotactic ablative body radiotherapy (SABR) for prostate adenocarcinoma to gain deeper insights into how radiotherapy (RT) modulates the immune system. Patients and methods RT-qPCR, flow cytometry, metabolomics, and antibody arrays were used to monitor a panel of stress- and immune-related parameters before RT, after the first fraction (SABR) or the first week of treatment (IMRT), after the last fraction, and 3 weeks later in the blood of IMRT (N & x202f;= 4) or SABR (N & x202f;= 4) patients. Effect size analysis was used for comparison of results at different timepoints. Results Several parameters were found to be differentially modulated in IMRT and SABR patients: the expression ofTGFB1,IL1B, andCCL3genes; the expression of HLA-DR on circulating monocytes; the abundance and ratio of phosphatidylcholine and lysophosphatidylcholine metabolites in plasma. More immune modulators in plasma were modulated during IMRT than SABR, with only two common proteins, namely GDF-15 and Tim-3. Conclusion Locally delivered RT induces systemic modulation of the immune system in prostate adenocarcinoma patients. IMRT and SABR appear to specifically affect distinct immune components.}, keywords = {immunophenotyping; ionizing radiation; Prostate cancer; Biomarkers of radiation exposure; Systemic immune modulation}, year = {2020}, eissn = {1439-099X}, pages = {1018-1033} }