title: Particle Radiation-Induced Nontargeted Effects in Bone-Marrow-Derived Endothelial Progenitor Cells.
abstract: Bone-marrow- (BM-) derived endothelial progenitor cells (EPCs) are critical for endothelial cell maintenance and repair. During future space exploration missions astronauts will be exposed to space irradiation (IR) composed of a spectrum of low-fluence protons ((1)H) and high charge and energy (HZE) nuclei (e.g., iron-(56)Fe) for extended time. How the space-type IR affects BM-EPCs is limited. In media transfer experiments in vitro we studied nontargeted effects induced by (1)H- and (56)Fe-IR conditioned medium (CM), which showed significant increase in the number of p-H2AX foci in nonirradiated EPCs between 2 and 24 h. A 2-15-fold increase in the levels of various cytokines and chemokines was observed in both types of IR-CM at 24 h. Ex vivo analysis of BM-EPCs from single, low-dose, full-body (1)H- and (56)Fe-IR mice demonstrated a cyclical (early 5-24 h and delayed 28 days) increase in apoptosis. This early increase in BM-EPC apoptosis may be the effect of direct IR exposure, whereas late increase in apoptosis could be a result of nontargeted effects (NTE) in the cells that were not traversed by IR directly. Identifying the role of specific cytokines responsible for IR-induced NTE and inhibiting such NTE may prevent long-term and cyclical loss of stem and progenitors cells in the BM milieu.
authors.affiliation: Cardiovascular Research Center, GeneSys Research Institute, Boston, MA 02135, USA.
authors.forename: Sharath P
authors.initials: SP
authors.lastname: Sasi
authors.affiliation: Cardiovascular Research Center, GeneSys Research Institute, Boston, MA 02135, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Park
authors.affiliation: Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Sujatha
authors.initials: S
authors.lastname: Muralidharan
authors.affiliation: Cardiovascular Research Center, GeneSys Research Institute, Boston, MA 02135, USA.
authors.forename: Justin
authors.initials: J
authors.lastname: Wage
authors.affiliation: Cardiovascular Research Center, GeneSys Research Institute, Boston, MA 02135, USA.
authors.forename: Albert
authors.initials: A
authors.lastname: Kiladjian
authors.affiliation: Cardiovascular Research Center, GeneSys Research Institute, Boston, MA 02135, USA.
authors.forename: Jillian
authors.initials: J
authors.lastname: Onufrak
authors.affiliation: Department of Integrated Mathematical Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
authors.forename: Heiko
authors.initials: H
authors.lastname: Enderling
authors.affiliation: Cardiovascular Research Center, GeneSys Research Institute, Boston, MA 02135, USA ; Tufts University School of Medicine, Boston, MA 02118, USA.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Yan
authors.affiliation: Cardiovascular Research Center, GeneSys Research Institute, Boston, MA 02135, USA ; Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA 02118, USA ; Tufts University School of Medicine, Boston, MA 02118, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Goukassian