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@ARTICLE{Abend:1010514,
author = {Abend, M. and Amundson, S. A. and Badie, C. and Brzoska, K.
and Hargitai, R. and Kriehuber, R. and Schüle, S. and Kis,
E. and Ghandhi, S. A. and Lumniczky, K. 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
Oestreicher, U. and Kulka, U. and Ristic, Y. and Trompier,
F. and Wojcik, A. and Waldner, L. and Port, M.},
title = {{I}nter-laboratory comparison of gene expression
biodosimetry for protracted radiation exposures as part of
the {RENEB} and {EURADOS} {WG}10 2019 exercise},
journal = {Scientific reports},
volume = {11},
number = {1},
issn = {2045-2322},
address = {[London]},
publisher = {Macmillan Publishers Limited, part of Springer Nature},
reportid = {FZJ-2023-03097},
pages = {9756},
year = {2021},
abstract = {Large-scale radiation emergency scenarios involving
protracted low dose rate radiation exposure (e.g. a hidden
radioactive source in a train) necessitate the development
of high throughput methods for providing rapid individual
dose estimates. During the RENEB (Running the European
Network of Biodosimetry) 2019 exercise, four EDTA-blood
samples were exposed to an Iridium-192 source (1.36 TBq,
Tech-Ops 880 Sentinal) at varying distances and geometries.
This resulted in protracted doses ranging between 0.2 and
2.4 Gy using dose rates of 1.5-40 mGy/min and exposure times
of 1 or 2.5 h. Blood samples were exposed in thermo bottles
that maintained temperatures between 39 and 27.7 °C. After
exposure, EDTA-blood samples were transferred into PAXGene
tubes to preserve RNA. RNA was isolated in one laboratory
and aliquots of four blinded RNA were sent to another five
teams for dose estimation based on gene expression changes.
Using an X-ray machine, samples for two calibration curves
(first: constant dose rate of 8.3 mGy/min and 0.5-8 h
varying exposure times; second: varying dose rates of
0.5-8.3 mGy/min and 4 h exposure time) were generated for
distribution. Assays were run in each laboratory according
to locally established protocols using either a microarray
platform (one team) or quantitative real-time PCR (qRT-PCR,
five teams). The qRT-PCR measurements were highly
reproducible with coefficient of variation below $15\%$ in
≥ $75\%$ of measurements resulting in reported dose
estimates ranging between 0 and 0.5 Gy in all samples and in
all laboratories. Up to twofold reductions in RNA copy
numbers per degree Celsius relative to 37 °C were observed.
However, when irradiating independent samples equivalent to
the blinded samples but increasing the combined exposure and
incubation time to 4 h at 37 °C, expected gene expression
changes corresponding to the absorbed doses were observed.
Clearly, time and an optimal temperature of 37 °C must be
allowed for the biological response to manifest as gene
expression changes prior to running the gene expression
assay. In conclusion, dose reconstructions based on gene
expression measurements are highly reproducible across
different techniques, protocols and laboratories. Even a
radiation dose of 0.25 Gy protracted over 4 h (1 mGy/min)
can be identified. These results demonstrate the importance
of the incubation conditions and time span between radiation
exposure and measurements of gene expression changes when
using this method in a field exercise or real emergency
situation.},
cin = {S-US},
ddc = {600},
cid = {I:(DE-Juel1)S-US-20090406},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {33963206},
UT = {WOS:000656464100007},
doi = {10.1038/s41598-021-88403-4},
url = {https://juser.fz-juelich.de/record/1010514},
}