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@INPROCEEDINGS{Unverricht:841302,
author = {Unverricht, Marcus and Boldt, Sonja and Giesen, Ulrich and
Pomplun, Ekkehard and Wolkenhauer, Olaf and Kriehuber, Ralf},
title = {{W}hole genome expression analysis in human {J}urkat cells
after exposure to {I}-123-iododeoxyuridine, γ-rays and
α-particles},
reportid = {FZJ-2017-08392},
year = {2011},
abstract = {Introduction: In order to develop a gene expression
profile-based method for biodosimetry purposes we used the
human p53-deficient T-lymphoma Jurkat cell line to study
whether gene signatures exist allowing the discrimination of
radiation quality.Methods: Equi-effect doses, i.e. radiation
doses and exposure conditions causing the same biological
effect level, were determined with regard to micronucleus
formation, γ-H2AX foci intensity and apoptosis induction
for the radiation qualities of γ-rays (Cs-137) and
α-particles (Am-241) as well as for the Auger electron
emitter I-123. Prior to the DNA-microarray based gene
expression experiments, Jurkat cells were either irradiated
with 0.8 and 5 Gy γ-rays, respectively with 0.1 and 0.5 Gy
α-particles or were exposed to 4 - 200 kBq
I-123-iododeoxyuridine (I-123-UdR) per 10E6 cells. I-123-UdR
was incorporated into the DNA for 20 h. After quantification
of cellular uptake and calculation of accumulated decays the
absorbed radiation dose was assessed based on the 3-D
geometry of the cells. RNA-isolation was performed 6 h and
24 h post-exposure. Whole human genome DNA-microarrays
(Agilent) were processed and expression profiles were
analyzed. Genes showing significant expression changes after
irradiation were identified by one-way ANOVA and Tukey-HSD
post-hoc testing. The biological functions of significantly
regulated genes were further investigated.Results:
Preliminary results of the gene expression analysis indicate
that the expression of more and different genes is
significantly altered after exposure to I-123-UdR and
α-particles when compared to γ-irradiation. The functional
analysis of significantly changed genes reveals that
apoptosis relevant genes are enriched after exposure to
I-123-UdR and α-particles in comparison to γ-irradiation.
Conclusions: I-123-UdR and α-particles induce pronounced
alterations in gene expression when compared to γ-rays.
Changes in the gene expression of p53-dependent
apoptosis-related genes were observed suggesting
p53-independent back-up pathways for apoptosis signalling in
Jurkat cells.Funded by Bundesministerium für Bildung und
Forschung (BMBF), Project No.: 02NUK005A and 02NUK005D},
month = {Aug},
date = {2011-08-24},
organization = {7th International Symposium on
Physical, Molecular, Cellular and
Medical Aspects of Auger Processes
2011, Jülich (Germany), 24 Aug 2011 -
26 Aug 2011},
subtyp = {After Call},
cin = {S-US},
cid = {I:(DE-Juel1)S-US-20090406},
pnm = {899 - ohne Topic (POF3-899)},
pid = {G:(DE-HGF)POF3-899},
typ = {PUB:(DE-HGF)24},
url = {https://juser.fz-juelich.de/record/841302},
}