PMID- 31550191 OWN - NLM STAT- MEDLINE DCOM- 20200123 LR - 20200123 IS - 1362-3095 (Electronic) IS - 0955-3002 (Linking) VI - 95 IP - 12 DP - 2019 Dec TI - Construction of fluorescence in situ hybridization (FISH) translocation dose-response calibration curve with multiple donor data sets using R, based on ISO 20046:2019 recommendations. PG - 1668-1684 LID - 10.1080/09553002.2019.1664788 [doi] AB - Purpose: Dose-response curve (DRC) generation is an important aspect in cytogenetic biodosimetry for accurate dose estimation for individuals suspected of prior irradiation. DRC construction with dicentric chromosomes after acute radiation is well-established following the publication of the IAEA EPR-Biodosimetry 2011 and ISO 19238:2014. However, the short half-life of dicentrics might not be suitable for retrospective dose estimation in radiation medical workers, radiation accident clean-up workers and the general public living in areas with higher than average amount of radiation. There is an urgent need for a chromosome translocation-based DRC, which is constructed based on translocation identification with fluorescence in situ hybridization (FISH). Despite several attempts to generate such a DRC in the past 40 years, no internationally standardized protocol has been developed until 2019, resulting in possible statistical uncertainties between DRCs previously generated.Materials and methods: Using the recently published ISO 20049:2019, a DRC from five healthy donors (four males: 23, 35, 44, 55 years old, one female: 33 years old) was generated with age-adjusted translocations scored per cell equivalent (age-adjusted Tr/CE), using a modified R-script previously published in EPR-Biodosimetry, for (60)Co gamma-ray doses of 0, 0.01, 0.02, 0.05, 0.1, 0.2, 0.5 and 1 Gy. The translocation data set used, based on probes used for chromosomes number 1, 2, and 4, was previously published by Abe et al. in 2018.Results: The results output from R include the DRC coefficients (C, alpha, beta), their p-values, the goodness-of-fit Pearson's chi square value and its corresponding p-value, and the DRC with its 95% confidence interval (CI). The equation of the DRC obtained was 0.0005 (+/-0.0001) +0.0178 (+/-0.0037) D + 0.0901 (+/-0.0054) D(2). DRC generated with averaged Tr/CE had a wider 95% CI than DRC generated with pooled Tr/CE, resulting in a 1.3-1.5 times increase in estimated dose range. No outliers between alpha coefficients from previously published modified DRCs and our DRC were detected with robust Z-score.Conclusions: ISO 20046:2019 should be referenced for future FISH translocation-based DRC generation to ensure statistical reliability of dose estimation. Important considerations for FISH translocation-based DRC up to 1 Gy include scoring more than 2000 CE per dose, the use of multiple donors, age-adjustment of observed translocations, the use of a minimum of 5 dose points including 0 Gy, scoring of total simple translocations in only stable cells and the decision of using pooled or averaged age-adjusted Tr/CE. FAU - Goh, Valerie Swee Ting AU - Goh VST AUID- ORCID: 0000-0002-0016-609X AD - Department of Bioscience and Laboratory Medicine, Graduate School of Health Sciences, Hirosaki University, Hirosaki, Japan. FAU - Fujishima, Yohei AU - Fujishima Y AUID- ORCID: 0000-0001-5053-3276 AD - Department of Bioscience and Laboratory Medicine, Graduate School of Health Sciences, Hirosaki University, Hirosaki, Japan. AD - Department of Radiation Biology, Tohoku University School of Medicine, Sendai, Japan. FAU - Abe, Yu AU - Abe Y AD - Department of Radiation Life Sciences, Fukushima Medical University School of Medicine, Fukushima, Japan. FAU - Sakai, Akira AU - Sakai A AUID- ORCID: 0000-0003-0128-8395 AD - Department of Radiation Life Sciences, Fukushima Medical University School of Medicine, Fukushima, Japan. FAU - Yoshida, Mitsuaki A AU - Yoshida MA AD - Department of Radiation Biology, Institute of Radiation Emergency Medicine, Hirosaki University, Hirosaki, Japan. FAU - Ariyoshi, Kentaro AU - Ariyoshi K AUID- ORCID: 0000-0002-4639-6130 AD - Department of Radiation Biology, Institute of Radiation Emergency Medicine, Hirosaki University, Hirosaki, Japan. FAU - Kasai, Kosuke AU - Kasai K AD - Department of Bioscience and Laboratory Medicine, Graduate School of Health Sciences, Hirosaki University, Hirosaki, Japan. FAU - Wilkins, Ruth C AU - Wilkins RC AUID- ORCID: 0000-0002-9621-477X AD - Consumer and Clinical Radiation Protection Bureau, Healthy Environments and Consumer Safety Branch, Ottawa, ON, Canada. FAU - Blakely, William F AU - Blakely WF AD - Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. FAU - Miura, Tomisato AU - Miura T AUID- ORCID: 0000-0003-3104-2134 AD - Department of Bioscience and Laboratory Medicine, Graduate School of Health Sciences, Hirosaki University, Hirosaki, Japan. AD - Department of Radiation Biology, Institute of Radiation Emergency Medicine, Hirosaki University, Hirosaki, Japan. LA - eng PT - Journal Article PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20190924 PL - England TA - Int J Radiat Biol JT - International journal of radiation biology JID - 8809243 SB - IM MH - Adult MH - Calibration MH - *Dose-Response Relationship, Radiation MH - Female MH - Healthy Volunteers MH - Humans MH - *In Situ Hybridization, Fluorescence MH - Male MH - Middle Aged MH - Translocation, Genetic/*radiation effects MH - Young Adult OTO - NOTNLM OT - Fluorescence in situ hybridization OT - biodosimetry OT - chromosome translocation OT - dose-response curve EDAT- 2019/09/25 06:00 MHDA- 2020/01/24 06:00 CRDT- 2019/09/25 06:00 PHST- 2019/09/25 06:00 [pubmed] PHST- 2020/01/24 06:00 [medline] PHST- 2019/09/25 06:00 [entrez] AID - 10.1080/09553002.2019.1664788 [doi] PST - ppublish SO - Int J Radiat Biol. 2019 Dec;95(12):1668-1684. doi: 10.1080/09553002.2019.1664788. Epub 2019 Sep 24.