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@INPROCEEDINGS{Schmitz:203507,
author = {Schmitz, Sabine and Oskamp, Dominik and Pomplun, Ekkehard
and Kriehuber, Ralf},
title = {{C}hromosome {A}berrations induced by the {A}uger electron
emitter {I}-125},
reportid = {FZJ-2015-05428},
year = {2015},
abstract = {Introduction: DNA-associated Auger-electron emitters (AEE)
cause cellular damage leading to high-LET type cell survival
curves indicating an enhanced relative biological
effectiveness. DNA double strand breaks (DSBs) induced by
Iodine-125-deoxyuridine (I-125-UdR) decays are claimed to be
very complex. To elucidate the assumed genotoxic potential
of DNA-associated AEE, chromosome aberrations were analyzed
in I-125-UdR-exposed human peripheral blood lymphocytes
(PBL). Methods: PBL were isolated from whole blood and
stimulated with chromosome medium containing
phytohaemagglutinin (PHA). After 24 h cultures were labelled
with I-125-UdR for 18 h (activity concentration 1 – 45
kBq) during the S-phase. Following standard cytogenetic
procedure, at least 100 metaphases were analyzed
microscopically for each activity concentration. Cell death
was measured by apoptosis assay using flow cytometry.
Radiation doses were determined by using point kernel
calculations.Results: After 18 h labeling with I-125-UdR the
cell cycle distribution is severely disturbed. About 40 $\%$
of PBL are fully labeled and 20 $\%$ show a moderate
labeling of I-125-UdR, whereas 40 $\%$ of cells remain
unlabeled. I-125-UdR primarily induces chromatid-type
aberrations. The dose-response relationship fits well to a
polynomial curve in the low dose range, whereas a linear fit
supplies a better estimation in the high dose range. Even
the lowest dose of 0.2 Gy leads to significant damage and to
a 13-fold increase of aberrations compared to the controls.
On average every fifth I-125-decay produces a single
chromatid aberration in PBL. In addition, a dose-dependent
increase of cell death is observed. Conclusions: I-125-UdR
has a very strong genotoxic capacity in human PBL even at
very low cellular doses of about 0.2 Gy. Efficiently labeled
cells displaying a prolonged cell cycle compared to
moderately labeled cells and cell death contribute
substantially to the desynchronisation of the cell cycle.
Our data, showing that one I-125-decay induces 0.2
chromatid aberrations, are in very good accordance to the
data of Sedelnikova [1] and Yasui [2] who found 0.26 DSB
per decay, indicating that approximately every DSB is
converted into a chromatid aberration.[1] O.A. Sedelnikova
et al. Radiation Research 158, 486 (2002)[2] L.S. Yasui,
Int. J. Radiat. Biol., 80, 895 (2004)},
month = {May},
date = {2015-05-20},
organization = {8th International Symposium on
Physical, Molecular, Cellular and
Medical Aspects of Auger Process, Kyoto
(Japan), 20 May 2015 - 22 May 2015},
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/203507},
}