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Title: Ectopically hTERT expressing adult human mesenchymal stem cells are less radiosensitive than their telomerase negative counterpart

Abstract

During the past several years increasing evidence indicating that the proliferation capacity of mammalian cells is highly radiosensitive, regardless of the species and the tissue of origin of the cells, has accumulated. It has also been shown that normal bone marrow cells of mice have a similar radiosensitivity to other mammalian cells so far tested. In this study, we investigated the genetic effects of ionizing radiation (2.5-15 Gy) on normal human mesenchymal stem cells and their telomerised counterpart hMSC-telo1. We evaluated overall genomic integrity, DNA damage/repair by applying a fluorescence-detected alkaline DNA unwinding assay together with Western blot analyses for phosphorylated H2AX and Q-FISH was applied for investigation of telomeric damage. Our results indicate that hMSC and TERT-immortalized hMSCs can cope with relatively high doses of {gamma}-rays and that overall DNA repair is similar in the two cell lines. The telomeres were extensively destroyed after irradiation in both cell types suggesting that telomere caps are especially sensitive to radiation. The TERT-immortalized hMSCs showed higher stability at telomeric regions than primary hMSCs indicating that cells with long telomeres and high telomerase activity have the advantage of re-establishing the telomeric caps.

Authors:
 [1];  [2];  [3];  [4];  [4];  [5];  [6];  [3]
  1. Department of Human Genetics, University of Aarhus, Aarhus (Denmark) and Institute of Medical Biology, Department of Anatomy and Neurobiology, Southern Denmark University, Odense (Denmark). E-mail: nserakinci@health.sdu.dk
  2. Department of Human Genetics, University of Aarhus, Aarhus (Denmark)
  3. Department of Clinical Genetics, Vejle County Hospital, Vejle (Denmark)
  4. Centre for Oncology and Applied Pharmacology, University of Glasgow, Cancer Research UK, Beatson Laboratories, Garscube Estate, Glasgow (United Kingdom)
  5. Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus (Denmark)
  6. Henry Wellcome Laboratory for Biogerontology, Newcastle General Hospital, University of Newcastle upon Tyne, Newcastle (United Kingdom)
Publication Date:
OSTI Identifier:
20972133
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Cell Research; Journal Volume: 313; Journal Issue: 5; Other Information: DOI: 10.1016/j.yexcr.2007.01.002; PII: S0014-4827(07)00006-7; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRONMENTAL POLLUTANT EFFECTS ON LIVING ORGANISMS AND BIOLOGICAL MATERIALS; BONE MARROW CELLS; DNA DAMAGES; DNA REPAIR; FLUORESCENCE; GAMMA RADIATION; GENETIC RADIATION EFFECTS; MICE; RADIOSENSITIVITY; STEM CELLS; TELOMERES

Citation Formats

Serakinci, Nedime, Christensen, Rikke, Graakjaer, Jesper, Cairney, Claire J., Keith, W. Nicol, Alsner, Jan, Saretzki, Gabriele, and Kolvraa, Steen. Ectopically hTERT expressing adult human mesenchymal stem cells are less radiosensitive than their telomerase negative counterpart. United States: N. p., 2007. Web. doi:10.1016/j.yexcr.2007.01.002.
Serakinci, Nedime, Christensen, Rikke, Graakjaer, Jesper, Cairney, Claire J., Keith, W. Nicol, Alsner, Jan, Saretzki, Gabriele, & Kolvraa, Steen. Ectopically hTERT expressing adult human mesenchymal stem cells are less radiosensitive than their telomerase negative counterpart. United States. doi:10.1016/j.yexcr.2007.01.002.
Serakinci, Nedime, Christensen, Rikke, Graakjaer, Jesper, Cairney, Claire J., Keith, W. Nicol, Alsner, Jan, Saretzki, Gabriele, and Kolvraa, Steen. Sat . "Ectopically hTERT expressing adult human mesenchymal stem cells are less radiosensitive than their telomerase negative counterpart". United States. doi:10.1016/j.yexcr.2007.01.002.
@article{osti_20972133,
title = {Ectopically hTERT expressing adult human mesenchymal stem cells are less radiosensitive than their telomerase negative counterpart},
author = {Serakinci, Nedime and Christensen, Rikke and Graakjaer, Jesper and Cairney, Claire J. and Keith, W. Nicol and Alsner, Jan and Saretzki, Gabriele and Kolvraa, Steen},
abstractNote = {During the past several years increasing evidence indicating that the proliferation capacity of mammalian cells is highly radiosensitive, regardless of the species and the tissue of origin of the cells, has accumulated. It has also been shown that normal bone marrow cells of mice have a similar radiosensitivity to other mammalian cells so far tested. In this study, we investigated the genetic effects of ionizing radiation (2.5-15 Gy) on normal human mesenchymal stem cells and their telomerised counterpart hMSC-telo1. We evaluated overall genomic integrity, DNA damage/repair by applying a fluorescence-detected alkaline DNA unwinding assay together with Western blot analyses for phosphorylated H2AX and Q-FISH was applied for investigation of telomeric damage. Our results indicate that hMSC and TERT-immortalized hMSCs can cope with relatively high doses of {gamma}-rays and that overall DNA repair is similar in the two cell lines. The telomeres were extensively destroyed after irradiation in both cell types suggesting that telomere caps are especially sensitive to radiation. The TERT-immortalized hMSCs showed higher stability at telomeric regions than primary hMSCs indicating that cells with long telomeres and high telomerase activity have the advantage of re-establishing the telomeric caps.},
doi = {10.1016/j.yexcr.2007.01.002},
journal = {Experimental Cell Research},
number = 5,
volume = 313,
place = {United States},
year = {Sat Mar 10 00:00:00 EST 2007},
month = {Sat Mar 10 00:00:00 EST 2007}
}