Oncotarget

Research Papers:

Low dose radiation induced senescence of human mesenchymal stromal cells and impaired the autophagy process

Nicola Alessio _, Stefania Del Gaudio, Stefania Capasso, Giovanni Di Bernardo, Salvatore Cappabianca, Marilena Cipollaro, Gianfranco Peluso and Umberto Galderisi

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Oncotarget. 2015; 6:8155-8166. https://doi.org/10.18632/oncotarget.2692

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Abstract

Nicola Alessio2, Stefania Del Gaudio2, Stefania Capasso2, Giovanni Di Bernardo2, Salvatore Cappabianca4, Marilena Cipollaro2, Gianfranco Peluso3, Umberto Galderisi1,2,3

1Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Temple University, Philadelphia, PA 19107-6799, USA

2Department of Experimental Medicine, Biotechnology and Molecular Biology Section, Second University of Naples, Naples 80138, Italy

3Institute of Bioscience and Bioresources, CNR, Naples 80138, Italy

4Department “F. Magrassi – A. Lanzara” Second University of Naples, Naples 80138, Italy

Correspondence to:

Umberto Galderisi, e-mail: tud23058@temple.edu

Keywords: Mesenchymal stem cells, senescence, radiation

Received: August 18, 2014     Accepted: November 02, 2014     Published: December 11, 2014

ABSTRACT

Low doses of radiation may have profound effects on cellular function. Individuals may be exposed to low doses of radiation either intentionally for medical purposes or accidentally, such as those exposed to radiological terrorism or those who live near illegal radioactive waste dumpsites.

We studied the effects of low dose radiation on human bone marrow mesenchymal stromal cells (MSC), which contain a subpopulation of stem cells able to differentiate in bone, cartilage, and fat; support hematopoiesis; and contribute to body’s homeostasis.

The main outcome of low radiation exposure, besides reduction of cell cycling, is the triggering of senescence, while the contribution to apoptosis is minimal. We also showed that low radiation affected the autophagic flux. We hypothesize that the autophagy prevented radiation deteriorative processes, and its decline contributed to senescence.

An increase in ATM staining one and six hours post-irradiation and return to basal level at 48 hours, along with persistent gamma-H2AX staining, indicated that MSC properly activated the DNA repair signaling, though some damages remained unrepaired, mainly in non-cycling cells. This suggested that the impaired DNA repair capacity of irradiated MSC seemed mainly related to the reduced activity of a non-homologous end-joining (NHEJ) system rather than HR (homologous recombination).


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