title: Biological effects of high-energy neutrons measured in vivo using a vertebrate model.
abstract: Interaction of solar protons and galactic cosmic radiation with the atmosphere and other materials produces high-energy secondary neutrons from below 1 to 1000 MeV and higher. Although secondary neutrons may provide an appreciable component of the radiation dose equivalent received by space and high-altitude air travelers, the biological effects remain poorly defined, particularly in vivo in intact organisms. Here we describe the acute response of Japanese medaka (Oryzias latipes) embryos to a beam of high-energy spallation neutrons that mimics the energy spectrum of secondary neutrons encountered aboard spacecraft and high-altitude aircraft. To determine RBE, embryos were exposed to 0-0.5 Gy of high-energy neutron radiation or 0-15 Gy of reference gamma radiation. The radiation response was measured by imaging apoptotic cells in situ in defined volumes of the embryo, an assay that provides a quantifiable, linear dose response. The slope of the dose response in the developing head, relative to reference gamma radiation, indicates an RBE of 24.9 (95% CI 13.6-40.7). A higher RBE of 48.1 (95% CI 30.0-66.4) was obtained based on overall survival. A separate analysis of apoptosis in muscle showed an overall nonlinear response, with the greatest effects at doses of less than 0.3 Gy. Results of this experiment indicate that medaka are a useful model for investigating biological damage associated with high-energy neutron exposure.
authors.affiliation: Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, Georgia 30912, USA. wkuhne@mcg.edu
authors.forename: Wendy W
authors.initials: WW
authors.lastname: Kuhne
authors.forename: Brad B
authors.initials: BB
authors.lastname: Gersey
authors.forename: Richard
authors.initials: R
authors.lastname: Wilkins
authors.forename: Honglu
authors.initials: H
authors.lastname: Wu
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Wender
authors.forename: Varghese
authors.initials: V
authors.lastname: George
authors.forename: William S
authors.initials: WS
authors.lastname: Dynan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D015415:Biomarkers / Q000378:metabolism; D004249:DNA Damage / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D023381:Endpoint Determination; D023421:Models, Animal; D009132:Muscles / Q000166:cytology / Q000528:radiation effects; D009502:Neutrons / Q000009:adverse effects*; D009990:Oryzias / Q000033:anatomy & histology / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D015415:Biomarkers; D016159:Tumor Suppressor Protein p53