Galactic Cosmic Radiation Induces Persistent Epigenome Alterations Relevant to Human Lung Cancer

Abstract Human deep space and planetary travel is limited by uncertainties regarding the health risks associated with exposure to galactic cosmic radiation (GCR), and in particular the high linear energy transfer (LET), heavy ion component. Here we assessed the impact of two high-LET ions 56Fe and 2...

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Autores principales:	E. M. Kennedy, D. R. Powell, Z. Li, J. S. K. Bell, B. G. Barwick, H. Feng, M. R. McCrary, B. Dwivedi, J. Kowalski, W. S. Dynan, K. N. Conneely, P. M. Vertino
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f87b1595000d46c19a007139a1f7607b
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spelling	oai:doaj.org-article:f87b1595000d46c19a007139a1f7607b2021-12-02T11:41:15ZGalactic Cosmic Radiation Induces Persistent Epigenome Alterations Relevant to Human Lung Cancer10.1038/s41598-018-24755-82045-2322https://doaj.org/article/f87b1595000d46c19a007139a1f7607b2018-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-24755-8https://doaj.org/toc/2045-2322Abstract Human deep space and planetary travel is limited by uncertainties regarding the health risks associated with exposure to galactic cosmic radiation (GCR), and in particular the high linear energy transfer (LET), heavy ion component. Here we assessed the impact of two high-LET ions 56Fe and 28Si, and low-LET X rays on genome-wide methylation patterns in human bronchial epithelial cells. We found that all three radiation types induced rapid and stable changes in DNA methylation but at distinct subsets of CpG sites affecting different chromatin compartments. The 56Fe ions induced mostly hypermethylation, and primarily affected sites in open chromatin regions including enhancers, promoters and the edges (“shores”) of CpG islands. The 28Si ion-exposure had mixed effects, inducing both hyper and hypomethylation and affecting sites in more repressed heterochromatic environments, whereas X rays induced mostly hypomethylation, primarily at sites in gene bodies and intergenic regions. Significantly, the methylation status of 56Fe ion sensitive sites, but not those affected by X ray or 28Si ions, discriminated tumor from normal tissue for human lung adenocarcinomas and squamous cell carcinomas. Thus, high-LET radiation exposure leaves a lasting imprint on the epigenome, and affects sites relevant to human lung cancer. These methylation signatures may prove useful in monitoring the cumulative biological impact and associated cancer risks encountered by astronauts in deep space.E. M. KennedyD. R. PowellZ. LiJ. S. K. BellB. G. BarwickH. FengM. R. McCraryB. DwivediJ. KowalskiW. S. DynanK. N. ConneelyP. M. VertinoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-14 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q E. M. Kennedy D. R. Powell Z. Li J. S. K. Bell B. G. Barwick H. Feng M. R. McCrary B. Dwivedi J. Kowalski W. S. Dynan K. N. Conneely P. M. Vertino Galactic Cosmic Radiation Induces Persistent Epigenome Alterations Relevant to Human Lung Cancer
description	Abstract Human deep space and planetary travel is limited by uncertainties regarding the health risks associated with exposure to galactic cosmic radiation (GCR), and in particular the high linear energy transfer (LET), heavy ion component. Here we assessed the impact of two high-LET ions 56Fe and 28Si, and low-LET X rays on genome-wide methylation patterns in human bronchial epithelial cells. We found that all three radiation types induced rapid and stable changes in DNA methylation but at distinct subsets of CpG sites affecting different chromatin compartments. The 56Fe ions induced mostly hypermethylation, and primarily affected sites in open chromatin regions including enhancers, promoters and the edges (“shores”) of CpG islands. The 28Si ion-exposure had mixed effects, inducing both hyper and hypomethylation and affecting sites in more repressed heterochromatic environments, whereas X rays induced mostly hypomethylation, primarily at sites in gene bodies and intergenic regions. Significantly, the methylation status of 56Fe ion sensitive sites, but not those affected by X ray or 28Si ions, discriminated tumor from normal tissue for human lung adenocarcinomas and squamous cell carcinomas. Thus, high-LET radiation exposure leaves a lasting imprint on the epigenome, and affects sites relevant to human lung cancer. These methylation signatures may prove useful in monitoring the cumulative biological impact and associated cancer risks encountered by astronauts in deep space.
format	article
author	E. M. Kennedy D. R. Powell Z. Li J. S. K. Bell B. G. Barwick H. Feng M. R. McCrary B. Dwivedi J. Kowalski W. S. Dynan K. N. Conneely P. M. Vertino
author_facet	E. M. Kennedy D. R. Powell Z. Li J. S. K. Bell B. G. Barwick H. Feng M. R. McCrary B. Dwivedi J. Kowalski W. S. Dynan K. N. Conneely P. M. Vertino
author_sort	E. M. Kennedy
title	Galactic Cosmic Radiation Induces Persistent Epigenome Alterations Relevant to Human Lung Cancer
title_short	Galactic Cosmic Radiation Induces Persistent Epigenome Alterations Relevant to Human Lung Cancer
title_full	Galactic Cosmic Radiation Induces Persistent Epigenome Alterations Relevant to Human Lung Cancer
title_fullStr	Galactic Cosmic Radiation Induces Persistent Epigenome Alterations Relevant to Human Lung Cancer
title_full_unstemmed	Galactic Cosmic Radiation Induces Persistent Epigenome Alterations Relevant to Human Lung Cancer
title_sort	galactic cosmic radiation induces persistent epigenome alterations relevant to human lung cancer
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/f87b1595000d46c19a007139a1f7607b
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Galactic Cosmic Radiation Induces Persistent Epigenome Alterations Relevant to Human Lung Cancer

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