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

• Type of Material: Article
• Authors: E.M. Kennedy, Emory University; D.R. Powell, Emory University; Z. Li, Emory University; J.S.K. Bell, Emory University; B.G. Barwick, Emory University; H. Feng, Emory University; M.R. McCrary, Emory University; Bhakti Dwivedi, Emory University; Jeanne Kowalski, Emory University; William Dynan, Emory University; Karen N Conneely, Emory University; Paula M Vertino, Emory University
• Language: English
• Date: 2018-04-30
• Publisher: Nature Publishing Group: Open Access Journals - Option C
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2018
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41598-018-24755-8
• Title of Journal or Parent Work: Scientific Reports
• ISSN: 2045-2322
• Volume: 8
• Start Page: 6709
• End Page: 6709
• Grant/Funding Information: Supported by the US National Aeronautics and Space Administration NSCOR Program grant NNX11AC30G (to PMV and WSD) and NNX15AD63G (to WSD).; This project was supported in part by the Winship Biostatistics and Bioinformatics Shared Resource and the Emory Integrated Genomics Shared Resource with support of the NCI Cancer Center Support Grant 1P30- CA0138292 to the Winship Cancer Institute of Emory University.
• Keywords: MICROARRAY DATA; BREAST-CANCER; DNA METHYLATION STATUS; Science & Technology - Other Topics; Multidisciplinary Sciences; COLON-CANCER; HZE PARTICLES; Science & Technology; LINEAR-ENERGY-TRANSFER; CBA/CAJ MICE; EPIGENETIC ALTERATIONS; SPACE EXPLORATION; PARTICLE RADIATION
• Research Categories: Health Sciences, Radiology; Biology, Genetics; Health Sciences, Oncology

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.