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25 June 2019 Biomolecular Analysis of Beta Dose-Dependent Cutaneous Radiation Injury in a Porcine Model
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Abstract

While cutaneous radiation injury (CRI) is generally referenced as a consequence of a nuclear attack, it can also be caused by less dangerous events such as the use of dirty bombs, industrial radiological accidents, or accidental overexposure of beta (β) particle or gamma (γ) radiation sources in medical procedures. Although the gross clinical consequences of these injuries have been well documented, relatively little is known about the molecular changes underlying the progression of pathology. Here we describe a porcine model of cutaneous radiation injury after skin was exposed to strontium-90 b particle at doses of 16–42 Gy and characterize the anatomical and molecular changes over 70 days. The results show that irradiated sites displayed dosedependent increases in erythema and moist desquamation that peaked between days 35 and 42. Dose-dependent histopathological changes were observed, with higher doses exhibiting increased inflammation and epidermal hyperplasia beyond day 35. Furthermore, immunohistochemistry showed that exposure to 37 Gy β-particle radiation decreased epidermal cell proliferation and desmosomal junction proteins at day 70, suggesting compromised epidermal integrity. Metabolomic analysis of biopsies revealed dose- and time-dependent changes as high as 252-fold in several metabolites not previously linked to CRI. These alterations were seen in pathways reflecting protein degradation, oxidative stress, eicosanoid production, collagen matrix remodeling, mitochondrial stress, cell membrane composition and vascular disruption. Taken together, these data show that exposure to high doses of β particle damaged the molecular processes underlying skin integrity to a greater extent and for a longer period of time than has been shown previously. These findings further understanding of radiation-induced skin injury and serve as a foundation for the development and testing of potential therapeutics to treat CRI.

© 2019 by Radiation Research Society. All rights of reproduction in any form reserved
Luke R. Burnett, Alexis R. Gabard, Mac Robinson, J. Daniel Bourland, Jennifer E. Dorand, Stephen Dozier, Roy Xiao, Daniel C. Roy, and Michael Tytell "Biomolecular Analysis of Beta Dose-Dependent Cutaneous Radiation Injury in a Porcine Model," Radiation Research 192(2), 145-158, (25 June 2019). https://doi.org/10.1667/RR14283.1
Received: 5 October 2015; Accepted: 2 May 2019; Published: 25 June 2019
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