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@ARTICLE{Abend:811945,
author = {Abend, M. and Badie, C. and Quintens, R. and Kriehuber, R.
and Manning, G. and Macaeva, E. and Njima, M. and Oskamp, D.
and Strunz, S. and Moertl, S. and Doucha-Senf, S. and
Dahlke, S. and Menzel, J. and Port, M.},
title = {{E}xamining {R}adiation-{I}nduced {I}n {V}ivo and {I}n
{V}itro {G}ene {E}xpression {C}hanges of the {P}eripheral
{B}lood in {D}ifferent {L}aboratories for {B}iodosimetry
{P}urposes: {F}irst {RENEB} {G}ene {E}xpression {S}tudy},
journal = {Radiation research},
volume = {185},
number = {2},
issn = {1938-5404},
address = {Great Falls, Va.},
publisher = {Radiation Research Society},
reportid = {FZJ-2016-04255},
pages = {109 - 123},
year = {2016},
abstract = {The risk of a large-scale event leading to acute radiation
exposure necessitates the development of high-throughput
methods for providing rapid individual dose estimates. Our
work addresses three goals, which align with the directive
of the European Union's Realizing the European Network of
Biodosimetry project (EU-RENB): 1. To examine the
suitability of different gene expression platforms for
biodosimetry purposes; 2. To perform this examination using
blood samples collected from prostate cancer patients (in
vivo) and from healthy donors (in vitro); and 3. To compare
radiation-induced gene expression changes of the in vivo
with in vitro blood samples. For the in vitro part of this
study, EDTA-treated whole blood was irradiated immediately
after venipuncture using single X-ray doses (1 Gy/min(-1)
dose rate, 100 keV). Blood samples used to generate
calibration curves as well as 10 coded (blinded) samples
(0-4 Gy dose range) were incubated for 24 h in vitro, lysed
and shipped on wet ice. For the in vivo part of the study
PAXgene tubes were used and peripheral blood (2.5 ml) was
collected from prostate cancer patients before and 24 h
after the first fractionated 2 Gy dose of localized
radiotherapy to the pelvis [linear accelerator (LINAC), 580
MU/min, exposure 1-1.5 min]. Assays were run in each
laboratory according to locally established protocols using
either microarray platforms (2 laboratories) or qRT-PCR (2
laboratories). Report times on dose estimates were
documented. The mean absolute difference of estimated doses
relative to the true doses (Gy) were calculated. Doses were
also merged into binary categories reflecting aspects of
clinical/diagnostic relevance. For the in vitro part of the
study, the earliest report time on dose estimates was 7 h
for qRT-PCR and 35 h for microarrays. Methodological
variance of gene expression measurements (CV $≤10\%$ for
technical replicates) and interindividual variance
(≤twofold for all genes) were low. Dose estimates based on
one gene, ferredoxin reductase (FDXR), using qRT-PCR were as
precise as dose estimates based on multiple genes using
microarrays, but the precision decreased at doses ≥2 Gy.
Binary dose categories comprising, for example, unexposed
compared with exposed samples, could be completely
discriminated with most of our methods. Exposed prostate
cancer blood samples (n = 4) could be completely
discriminated from unexposed blood samples (n = 4, P < 0.03,
two-sided Fisher's exact test) without individual controls.
This could be performed by introducing an in vitro-to-in
vivo correction factor of FDXR, which varied among the
laboratories. After that the in vitro-constructed
calibration curves could be used for dose estimation of the
in vivo exposed prostate cancer blood samples within an
accuracy window of ±0.5 Gy in both contributing qRT-PCR
laboratories. In conclusion, early and precise dose
estimates can be performed, in particular at doses ≤2 Gy
in vitro. Blood samples of prostate cancer patients exposed
to 0.09-0.017 Gy could be completely discriminated from
pre-exposure blood samples with the doses successfully
estimated using adjusted in vitro-constructed calibration
curves.},
cin = {S-US},
ddc = {610},
cid = {I:(DE-Juel1)S-US-20090406},
pnm = {899 - ohne Topic (POF3-899)},
pid = {G:(DE-HGF)POF3-899},
typ = {PUB:(DE-HGF)16},
UT = {WOS:000370734200002},
doi = {10.1667/RR14221.1},
url = {https://juser.fz-juelich.de/record/811945},
}