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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2014
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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. |
format | Online Article Text |
id | pubmed-4100002 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
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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