In vitro relationships of galactic cosmic radiation and epigenetic clocks in human bronchial epithelial cells

• Type of Material: Article
• Authors: Jamaji Nwanaji-Enwerem, Emory University; Philippe Boileau, University of California Berkeley; Jonathan M Galazka, NASA Ames Research Center; Andres Cardenas, University of California Berkeley
• Language: English
• Date: 2022-05-12
• Publisher: WILEY
• Publication Version: Final Published Version
• Copyright Statement: © 2022 The Authors. Environmental and Molecular Mutagenesis published by Wiley Periodicals LLC on behalf of Environmental Mutagen Society.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1002/em.22483
• Title of Journal or Parent Work: ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
• Volume: 63
• Issue: 4
• Start Page: 184
• End Page: 189
• Grant/Funding Information: Jamaji C. Nwanaji‐Enwerem and Andres Cardenas are supported by the National Institutes of Health grants R03AG067064 and R01ES031259.; Philippe Boileau gratefully acknowledges the support of the Fonds de recherche du Québec—Nature et technologies and the Natural Sciences and Engineering Research Council of Canada.
• Keywords: Si; Life Sciences & Biomedicine; DNA METHYLATION; AGE; Science & Technology; Toxicology; radiation; Environmental Sciences; Genetics & Heredity; mitotic clock; SEQUENCE; Environmental Sciences & Ecology; epigenetic age; Fe; DNA methylation; X-ray
• Research Categories: Health Sciences, Public Health; Environmental Sciences

Abstract

Ionizing radiation is a well-appreciated health risk, precipitant of DNA damage, and contributor to DNA methylation variability. Nevertheless, relationships of ionizing radiation with DNA methylation-based markers of biological age (i.e. epigenetic clocks) remain poorly understood. Using existing data from human bronchial epithelial cells, we examined in vitro relationships of three epigenetic clock measures (Horvath DNAmAge, MiAge, and epiTOC2) with galactic cosmic radiation (GCR), which is particularly hazardous due to its high linear energy transfer (LET) heavy-ion components. High-LET 56Fe was significantly associated with accelerations in epiTOC2 (β = 192 cell divisions, 95% CI: 71, 313, p-value =.003). We also observed a significant, positive interaction of 56Fe ions and time-in-culture with epiTOC2 (95% CI: 42, 441, p-value =.019). However, only the direct 56Fe ion association remained statistically significant after adjusting for multiple hypothesis testing. Epigenetic clocks were not significantly associated with high-LET 28Si and low-LET X-rays. Our results demonstrate sensitivities of specific epigenetic clock measures to certain forms of GCR. These findings suggest that epigenetic clocks may have some utility for monitoring and better understanding the health impacts of GCR.