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@INPROCEEDINGS{Dahmen:841317,
author = {Dahmen, Volker and Kriehuber, Ralf},
title = {{C}ytotoxicity and induction of cell cycle arrest in
{SCL}-{II} cells after transfection with {I}-125 labeled
{T}riplex-{F}orming {O}ligonucleotides},
reportid = {FZJ-2017-08406},
year = {2012},
abstract = {Introduction: Triplex-forming oligonucleotides (TFOs) are
able to bind DNA in a sequence specific manner and are a
promising tool to manipulate genes or gene regulatory units
in a cellular environment. TFOs posses also a therapeutic
potential e.g. as a carrier molecule for Alpha- or
Auger-Electron-Emitter (AEE) to target specific DNA
sequences in tumor cells. We established a method for the
effective labeling of TFOs with the AEE iodine-125 (I-125)
and studied the influence of labeled TFOs in transfected
SCL-II cells with regard to cell survival, appearance of DNA
Double-Strand-Breaks (DSB) and the induction of cell cycle
arrest.Methods: The TFOs employed were a single binding site
TFO, specific for GAPDH and two multi-binding TFOs with
several thousand binding sites in the human genome. TFO
labeling with I-125 was performed using the primer extension
method. Cell survival and DNA DSB frequency in I-125-TFO
transfected SCL-II cells were analyzed with the
Colony-Forming-Assay and the 53BP1 Assay. Analysis of cell
cycle was done after 7-AAD staining by
flowcytometry.Results: All three tested TFOs induced a
pronounced cytotoxic effect on SCL-II cells. The broadest
effect was found for the TFO employing the highest target
number in the genome. Furthermore an increased frequency of
DSB and a significant cell cycle arrest in G2/M phase 8 h
post-transfection could be detected.Conclusion: I-125
labeled TFOs with multiple binding sites as well as single
binding TFOs do induce a pronounced cytotoxic effect and
increase the DSB frequency in SCL-II cells. Additionally
there is strong evidence that I-125-labeled TFOs can
influence the cell cycle course in transfected SCL-I cells.
Funded by the Bundesministerium für Bildung und Forschung
(BMBF), Kompetenzverbund Strahlenforschung (KVSF), Project
No.: 02NUK005A},
month = {Sep},
date = {2012-09-17},
organization = {15. Jahrestagung der Gesellschaft für
biologische Strahlenforschung, München
(Germany), 17 Sep 2012 - 20 Sep 2012},
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/841317},
}