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Lookup NU author(s): Dr Rachel Queen
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2022 The Author(s)Purpose: Radiation cardiotoxicity (RC) is a clinically significant adverse effect of treatment for patients with thoracic malignancies. Clinical studies in lung cancer have indicated that heart substructures are not uniformly radiosensitive, and that dose to the heart base drives RC. In this study, we aimed to characterize late changes in gene expression using spatial transcriptomics in a mouse model of base regional radiosensitivity. Methods and Materials: An aged female C57BL/6 mouse was irradiated with 16 Gy delivered to the cranial third of the heart using a 6 × 9 mm parallel opposed beam geometry on a small animal radiation research platform, and a second mouse was sham-irradiated. After echocardiography, whole hearts were collected at 30 weeks for spatial transcriptomic analysis to map gene expression changes occurring in different regions of the partially irradiated heart. Cardiac regions were manually annotated on the capture slides and the gene expression profiles compared across different regions. Results: Ejection fraction was reduced at 30 weeks after a 16 Gy irradiation to the heart base, compared with the sham-irradiated controls. There were markedly more significant gene expression changes within the irradiated regions compared with nonirradiated regions. Variation was observed in the transcriptomic effects of radiation on different cardiac base structures (eg, between the right atrium [n = 86 dysregulated genes], left atrium [n = 96 dysregulated genes], and the vasculature [n = 129 dysregulated genes]). Disrupted biological processes spanned extracellular matrix as well as circulatory, neuronal, and contractility activities. Conclusions: This is the first study to report spatially resolved gene expression changes in irradiated tissues. Examination of the regional radiation response in the heart can help to further our understanding of the cardiac base's radiosensitivity and support the development of actionable targets for pharmacologic intervention and biologically relevant dose constraints.
Author(s): Walls GM, Ghita M, Queen R, Edgar KS, Gill EK, Kuburas R, Grieve DJ, Watson CJ, McWilliam A, Van Herk M, Williams KJ, Cole AJ, Jain S, Butterworth KT
Publication type: Article
Publication status: Published
Journal: International Journal of Radiation Oncology*Biology*Physics
Year: 2023
Volume: 115
Issue: 2
Pages: 453-463
Print publication date: 01/02/2023
Online publication date: 17/08/2022
Acceptance date: 05/08/2022
Date deposited: 31/08/2023
ISSN (print): 0360-3016
ISSN (electronic): 1879-355X
Publisher: Elsevier Inc.
URL: https://doi.org/10.1016/j.ijrobp.2022.08.031
DOI: 10.1016/j.ijrobp.2022.08.031
Data Access Statement: The data are not available for sharing at the time of publication.
PubMed id: 35985456
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