title: Combined exposure to protons and (56)Fe leads to overexpression of Il13 and reactivation of repetitive elements in the mouse lung.
abstract: Interest in deep space exploration underlines the needs to investigate the effects of exposure to combined sources of space radiation. The lung is a target organ for radiation, and exposure to protons and heavy ions as radiation sources may lead to the development of degenerative disease and cancer. In this study, we evaluated the pro-fibrotic and epigenetic effects of exposure to protons (150 MeV/nucleon, 0.1 Gy) and heavy iron ions ((56)Fe, 600 MeV/nucleon, 0.5 Gy) alone or in combination (protons on Day 1 and (56)Fe on Day 2) in C57BL/6 male mice 4 weeks after irradiation. Exposure to (56)Fe, proton or in combination, did not result in histopathological changes in the murine lung. At the same time, combined exposure to protons and (56)Fe resulted in pronounced molecular alterations in comparison with either source of radiation alone. Specifically, we observed a substantial increase in the expression of cytokine Il13, loss of expression of DNA methyltransferase Dnmt1, and reactivation of LINE-1, SINE B1 retrotransposons, and major and minor satellites. Given the deleterious potential of the observed effects that may lead to development of chronic lung injury, pulmonary fibrosis, and cancer, future studies devoted to the investigation of the long-term effects of combined exposures to proton and heavy ions are clearly needed.
authors.affiliation: Department of Environmental Health, Fay W. Boozman College of Public Health, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA; Department of Biology, Indiana University, Bloomington, IN, 47405, USA.
authors.forename: Etienne
authors.initials: E
authors.lastname: Nzabarushimana
authors.affiliation: Department of Environmental Health, Fay W. Boozman College of Public Health, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Prior
authors.affiliation: Department of Environmental Health, Fay W. Boozman College of Public Health, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.
authors.forename: Isabelle R
authors.initials: IR
authors.lastname: Miousse
authors.affiliation: Division of Radiation Health, Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.
authors.forename: Rupak
authors.initials: R
authors.lastname: Pathak
authors.affiliation: Division of Radiation Health, Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.
authors.forename: Antiño R
authors.initials: AR
authors.lastname: Allen
authors.affiliation: Toxicologic Pathology Associates, Jefferson, AR, 72079, USA.
authors.forename: John
authors.initials: J
authors.lastname: Latendresse
authors.affiliation: Department of Behavioral Neuroscience, Oregon Health & Science University Portland, OR, 97239, USA.
authors.forename: Reid H J
authors.initials: RH
authors.lastname: Olsen
authors.affiliation: Departments of Neurology and Radiation Medicine, Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University Portland, OR, 97239, USA.
authors.forename: Jacob
authors.initials: J
authors.lastname: Raber
authors.affiliation: Division of Radiation Health, Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Hauer-Jensen
authors.affiliation: Department of Basic Sciences, Division of Radiation Research, Loma Linda University, Loma Linda, CA, 92350, USA.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Nelson
authors.affiliation: Department of Environmental Health, Fay W. Boozman College of Public Health, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA. Electronic address: ikoturbash@uams.edu.
authors.forename: Igor
authors.initials: I
authors.lastname: Koturbash
mesh_terms: D000818:Animals; D004307:Dose-Response Relationship, Radiation; D020450:Heavy Ions; D018793:Interleukin-13; D007501:Iron; D018499:Linear Energy Transfer; D008168:Lung; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011522:Protons; D012091:Repetitive Sequences, Nucleic Acid
chemical_list: D018793:Interleukin-13; D011522:Protons; D007501:Iron
keywords: Pulmonary fibrosis; Repetitive elements; Space radiation