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Long-term epigenetic effects of exposure to low doses of (56)Fe in the mouse lung

Despite significant progress, the long-term health effects of exposure to high charge (Z) and energy (E) nuclei (HZEs) and the underlying mechanisms remain poorly understood. Mouse studies show that space missions can result in pulmonary pathological states. The goal of this study was to evaluate th...

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Autores principales: Nzabarushimana, Etienne, Miousse, Isabelle R., Shao, Lijian, Chang, Jianhui, Allen, Antiño R., Turner, Jennifer, Stewart, Blair, Raber, Jacob, Koturbash, Igor
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4100002/
https://www.ncbi.nlm.nih.gov/pubmed/24585548
http://dx.doi.org/10.1093/jrr/rru010
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author Nzabarushimana, Etienne
Miousse, Isabelle R.
Shao, Lijian
Chang, Jianhui
Allen, Antiño R.
Turner, Jennifer
Stewart, Blair
Raber, Jacob
Koturbash, Igor
author_facet Nzabarushimana, Etienne
Miousse, Isabelle R.
Shao, Lijian
Chang, Jianhui
Allen, Antiño R.
Turner, Jennifer
Stewart, Blair
Raber, Jacob
Koturbash, Igor
author_sort Nzabarushimana, Etienne
collection PubMed
description Despite significant progress, the long-term health effects of exposure to high charge (Z) and energy (E) nuclei (HZEs) and the underlying mechanisms remain poorly understood. Mouse studies show that space missions can result in pulmonary pathological states. The goal of this study was to evaluate the pro-fibrotic and pro-carcinogenic effects of exposure to low doses of heavy iron ions ((56)Fe) in the mouse lung. Exposure to (56)Fe (600 MeV; 0.1, 0.2 and 0.4 Gy) resulted in minor pro-fibrotic changes, detected at the beginning of the fibrotic phase (22 weeks post exposure), which were exhibited as increased expression of chemokine Ccl3, and interleukin Il4. Epigenetic alterations were exhibited as global DNA hypermethylation, observed after exposure to 0.4 Gy. Cadm1, Cdh13, Cdkn1c, Mthfr and Sfrp1 were significantly hypermethylated after exposure to 0.1 Gy, while exposure to higher doses resulted in hypermethylation of Cdkn1c only. However, expression of these genes was not affected by any dose. Congruently with the observed patterns of global DNA methylation, DNA repetitive elements were hypermethylated after exposure to 0.4 Gy, with minor changes observed after exposure to lower doses. Importantly, hypermethylation of repetitive elements coincided with their transcriptional repression. The findings of this study will aid in understanding molecular determinants of pathological states associated with exposure to (56)Fe, as well as serve as robust biomarkers for the delayed effects of irradiation. Further studies are clearly needed to investigate the persistence and outcomes of molecular alterations long term after exposure.
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spelling pubmed-41000022014-08-12 Long-term epigenetic effects of exposure to low doses of (56)Fe in the mouse lung Nzabarushimana, Etienne Miousse, Isabelle R. Shao, Lijian Chang, Jianhui Allen, Antiño R. Turner, Jennifer Stewart, Blair Raber, Jacob Koturbash, Igor J Radiat Res Short Communications Despite significant progress, the long-term health effects of exposure to high charge (Z) and energy (E) nuclei (HZEs) and the underlying mechanisms remain poorly understood. Mouse studies show that space missions can result in pulmonary pathological states. The goal of this study was to evaluate the pro-fibrotic and pro-carcinogenic effects of exposure to low doses of heavy iron ions ((56)Fe) in the mouse lung. Exposure to (56)Fe (600 MeV; 0.1, 0.2 and 0.4 Gy) resulted in minor pro-fibrotic changes, detected at the beginning of the fibrotic phase (22 weeks post exposure), which were exhibited as increased expression of chemokine Ccl3, and interleukin Il4. Epigenetic alterations were exhibited as global DNA hypermethylation, observed after exposure to 0.4 Gy. Cadm1, Cdh13, Cdkn1c, Mthfr and Sfrp1 were significantly hypermethylated after exposure to 0.1 Gy, while exposure to higher doses resulted in hypermethylation of Cdkn1c only. However, expression of these genes was not affected by any dose. Congruently with the observed patterns of global DNA methylation, DNA repetitive elements were hypermethylated after exposure to 0.4 Gy, with minor changes observed after exposure to lower doses. Importantly, hypermethylation of repetitive elements coincided with their transcriptional repression. The findings of this study will aid in understanding molecular determinants of pathological states associated with exposure to (56)Fe, as well as serve as robust biomarkers for the delayed effects of irradiation. Further studies are clearly needed to investigate the persistence and outcomes of molecular alterations long term after exposure. Oxford University Press 2014-07 2014-02-28 /pmc/articles/PMC4100002/ /pubmed/24585548 http://dx.doi.org/10.1093/jrr/rru010 Text en © The Author 2014. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Short Communications
Nzabarushimana, Etienne
Miousse, Isabelle R.
Shao, Lijian
Chang, Jianhui
Allen, Antiño R.
Turner, Jennifer
Stewart, Blair
Raber, Jacob
Koturbash, Igor
Long-term epigenetic effects of exposure to low doses of (56)Fe in the mouse lung
title Long-term epigenetic effects of exposure to low doses of (56)Fe in the mouse lung
title_full Long-term epigenetic effects of exposure to low doses of (56)Fe in the mouse lung
title_fullStr Long-term epigenetic effects of exposure to low doses of (56)Fe in the mouse lung
title_full_unstemmed Long-term epigenetic effects of exposure to low doses of (56)Fe in the mouse lung
title_short Long-term epigenetic effects of exposure to low doses of (56)Fe in the mouse lung
title_sort long-term epigenetic effects of exposure to low doses of (56)fe in the mouse lung
topic Short Communications
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4100002/
https://www.ncbi.nlm.nih.gov/pubmed/24585548
http://dx.doi.org/10.1093/jrr/rru010
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