title: Radiation-induced changes in DNA methylation of repetitive elements in the mouse heart.
abstract: DNA methylation is a key epigenetic mechanism, needed for proper control over the expression of genetic information and silencing of repetitive elements. Exposure to ionizing radiation, aside from its strong genotoxic potential, may also affect the methylation of DNA, within the repetitive elements, in particular. In this study, we exposed C57BL/6J male mice to low absorbed mean doses of two types of space radiation-proton (0.1 Gy, 150 MeV, dose rate 0.53 ± 0.08 Gy/min), and heavy iron ions ((56)Fe) (0.5 Gy, 600 MeV/n, dose rate 0.38 ± 0.06 Gy/min). Radiation-induced changes in cardiac DNA methylation associated with repetitive elements were detected. Specifically, modest hypomethylation of retrotransposon LINE-1 was observed at day 7 after irradiation with either protons or (56)Fe. This was followed by LINE-1, and other retrotransposons, ERV2 and SINE B1, as well as major satellite DNA hypermethylation at day 90 after irradiation with (56)Fe. These changes in DNA methylation were accompanied by alterations in the expression of DNA methylation machinery and affected the one-carbon metabolism pathway. Furthermore, loss of transposable elements expression was detected in the cardiac tissue at the 90-day time-point, paralleled by substantial accumulation of mRNA transcripts, associated with major satellites. Given that the one-carbon metabolism pathway can be modulated by dietary modifications, these findings suggest a potential strategy for the mitigation and, possibly, prevention of the negative effects exerted by ionizing radiation on the cardiovascular system. Additionally, we show that the methylation status and expression of repetitive elements may serve as early biomarkers of exposure to space radiation.
authors.affiliation: Department of Environmental and Occupational Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States. Electronic address: ikoturbash@uams.edu.
authors.forename: Igor
authors.initials: I
authors.lastname: Koturbash
authors.affiliation: Department of Environmental and Occupational Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States.
authors.forename: Isabelle R
authors.initials: IR
authors.lastname: Miousse
authors.affiliation: Division of Radiation Health, Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States.
authors.forename: Vijayalakshmi
authors.initials: V
authors.lastname: Sridharan
authors.affiliation: Department of Environmental and Occupational Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States.
authors.forename: Etienne
authors.initials: E
authors.lastname: Nzabarushimana
authors.affiliation: Department of Environmental and Occupational Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States.
authors.forename: Charles M
authors.initials: CM
authors.lastname: Skinner
authors.affiliation: Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States.
authors.forename: Stepan B
authors.initials: SB
authors.lastname: Melnyk
authors.affiliation: Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States.
authors.forename: Oleksandra
authors.initials: O
authors.lastname: Pavliv
authors.affiliation: Division of Radiation Health, Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States; Surgical Service, Central Arkansas Veterans Healthcare System, Little Rock, AR 72205, United States.
authors.forename: Martin
authors.initials: M
authors.lastname: Hauer-Jensen
authors.affiliation: Departments of Basic Sciences and Radiation Medicine, Loma Linda University, Loma Linda, CA 92354, United States.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Nelson
authors.affiliation: Division of Radiation Health, Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States.
authors.forename: Marjan
authors.initials: M
authors.lastname: Boerma
mesh_terms: D000818:Animals; D004249:DNA Damage; D019175:DNA Methylation / Q000528:radiation effects*; D044127:Epigenesis, Genetic; D006321:Heart / Q000528:radiation effects*; D006331:Heart Diseases / Q000235:genetics; D020084:Long Interspersed Nucleotide Elements; D008297:Male; D008715:Methionine / Q000378:metabolism; D008810:Mice, Inbred C57BL; D011833:Radiation Injuries, Experimental / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D008715:Methionine
keywords: DNA methylation; Heart; One-carbon metabolism pathway; Repetitive elements; Space radiation