title: A priming dose of protons alters the early cardiac cellular and molecular response to (56)Fe irradiation.
abstract: OBJECTIVE
  Recent evidence suggests that the heart may be injured by ionizing radiation at lower doses than was previously thought. This raises concerns about the cardiovascular risks from exposure to radiation during space travel. Since space travel is associated with exposure to both protons from solar particle events and heavy ions from galactic cosmic rays, we here examined the effects of a "priming" dose of protons on the cardiac cellular and molecular response to a "challenge" dose of (56)Fe in a mouse model.
  
  
  METHODS
  Male C57BL/6 mice at 10 weeks of age were exposed to sham-irradiation, 0.1 Gy of protons (150 MeV), 0.5 Gy of (56)Fe (600 MeV/n), or 0.1 Gy of protons 24 hours prior to 0.5 Gy of (56)Fe. Hearts were obtained at 7 days post-irradiation and western-blots were used to determine protein markers of cardiac remodeling, inflammatory infiltration, and cell death.
  
  
  RESULTS
  Exposure to (56)Fe caused an increase in expression of α-smooth muscle cell actin, collagen type III, the inflammatory cell markers mast cell tryptase, CD2 and CD68, the endothelial glycoprotein thrombomodulin, and cleaved caspase 3. Of all proteins investigated, protons at a dose of 0.1 Gy induced a small increase only in cleaved caspase 3 levels. On the other hand, exposure to protons 24 hours before (56)Fe prevented all of the responses to (56)Fe.
  
  
  CONCLUSIONS
  This study shows that a low dose of protons may prime the heart to respond differently to a subsequent challenge dose of heavy ions. Further investigation is required to identify responses at additional time points, consequences for cardiac function, threshold dose levels, and mechanisms by which a proton priming dose may alter the response to heavy ions.
authors.affiliation: Division of Radiation Health, Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: Samy S
authors.initials: SS
authors.lastname: Ramadan
authors.affiliation: Division of Radiation Health, Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: Vijayalakshmi
authors.initials: V
authors.lastname: Sridharan
authors.affiliation: Department of Environmental and Occupational Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: Igor
authors.initials: I
authors.lastname: Koturbash
authors.affiliation: Department of Environmental and Occupational Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: Isabelle R
authors.initials: IR
authors.lastname: Miousse
authors.affiliation: Division of Radiation Health, Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA; Surgical Service, Central Arkansas Veterans Healthcare System, Little Rock, AR 72205, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Hauer-Jensen
authors.affiliation: Departments of Basic Sciences and Radiation Medicine, Loma Linda University, Loma Linda, CA 92354, USA.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Nelson
authors.affiliation: Division of Radiation Health, Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. Electronic address: mboerma@uams.edu.
authors.forename: Marjan
authors.initials: M
authors.lastname: Boerma
mesh_terms: D000818:Animals; D003359:Cosmic Radiation; D004307:Dose-Response Relationship, Radiation; D005720:Gamma Rays; D020450:Heavy Ions; D018499:Linear Energy Transfer; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011522:Protons; D011829:Radiation Dosage; D019445:Solar Activity
chemical_list: D011522:Protons
keywords: GCR; Heart; High-LET radiation; Inflammatory infiltration; SPE; Space radiation