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Life Sci Space Res (Amst). 2016 Feb;8:8-13. doi: 10.1016/j.lssr.2015.12.001. Epub 2015 Dec 14.

A priming dose of protons alters the early cardiac cellular and molecular response to (56)Fe irradiation.

Author information

1
Division of Radiation Health, Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
2
Department of Environmental and Occupational Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
3
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.
4
Departments of Basic Sciences and Radiation Medicine, Loma Linda University, Loma Linda, CA 92354, USA.
5
Division of Radiation Health, Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. Electronic address: mboerma@uams.edu.

Abstract

PURPOSE:

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.

KEYWORDS:

GCR; Heart; High-LET radiation; Inflammatory infiltration; SPE; Space radiation

PMID:
26948008
PMCID:
PMC4782196
DOI:
10.1016/j.lssr.2015.12.001
[Indexed for MEDLINE]
Free PMC Article

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