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Lung and Heart Injury in a Nonhuman Primate Model of Partial-body Irradiation with Minimal Bone Marrow Sparing

Histopathological Evidence of Lung and Heart Injury

Parker, George A.1; Li, Na1; Takayama, Kyle1; Farese, Ann M.2; MacVittie, Thomas J.2

doi: 10.1097/HP.0000000000000936
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Male rhesus macaques were subjected to partial-body irradiation at 10, 11, or 12 Gy with 5% bone marrow protection. Animals were euthanized when dictated by prospectively determined clinical parameters or at approximately 180 d following irradiation. Histological sections of lung and heart were stained with hematoxylin and eosin as well as a battery of histochemical and immunohistochemical stains. Histopathological alterations in the lung were centered on fibrosis, inflammation, and reactive/proliferative changes in pneumocytes. These changes were noted in animals necropsied after approximately 85–100 d postirradiation and extending through the observation period. Interstitial and pleural fibrosis demonstrated by Masson’s trichrome staining were associated with increased alpha smooth muscle actin and collagen 1 immunohistochemical staining. Areas of interstitial fibrosis had reduced microvascular density with CD31 immunohistochemical staining. Accumulations of CD163- and CD206-positive alveolar macrophages were present in areas of interstitial fibrosis. Unidentified cells termed “myxoid” cells in alveolar walls had histochemical and immunohistochemical staining characteristics of epithelial-, endothelial-, or pericyte-mesenchymal transition states that were developing myofibroblast features. Distinctive focal or multifocal alveolar-bronchiolar hyperplasia had microscopic features of preneoplastic proliferation. Delayed radiation-associated changes in the heart consisted primarily of myocardial fibrosis, with rare histological evidence of myofiber degeneration.

1Charles River Laboratories/Pathology Associates, Durham, NC;

2University of Maryland, School of Medicine, Department of Radiation Oncology, Baltimore, MD.

For correspondence contact George A. Parker, Charles River Laboratories/Pathology Associates, 4025 Stirrup Creek Drive, Suite 150, Durham, NC 27703, or email at george.parker@crl.com.

(Manuscript accepted 21 June 2018)

© 2019 by the Health Physics Society