title: Neurocytotoxic effects of iron-ions on the developing brain measured in vivo using medaka (Oryzias latipes), a vertebrate model.
abstract: OBJECTIVE
  Exposure to heavy-ion radiation is considered a critical health risk on long-term space missions. The developing central nervous system (CNS) is a highly radiosensitive tissue; however, the biological effects of heavy-ion radiation, which are greater than those of low-linear energy transfer (LET) radiation, are not well studied, especially in vivo in intact organisms. Here, we examined the effects of iron-ions on the developing CNS using vertebrate organism, fish embryos of medaka (Oryzias latipes).
  
  
  METHODS
  Medaka embryos at developmental stage 28 were irradiated with iron-ions at various doses of 0-1.5 Gy. At 24 h after irradiation, radiation-induced apoptosis was examined using an acridine orange (AO) assay and histologically. To estimate the relative biological effectiveness (RBE), we quantified only characteristic AO-stained rosette-shaped apoptosis in the developing optic tectum (OT). At the time of hatching, morphological abnormalities in the irradiated brain were examined histologically.
  
  
  RESULTS
  The dose-response curve utilizing an apoptotic index for the iron-ion irradiated embryos was much steeper than that for X-ray irradiated embryos, with RBE values of 3.7-4.2. Histological examinations of irradiated medaka brain at 24 h after irradiation showed AO-positive rosette-shaped clusters as aggregates of condensed nuclei, exhibiting a circular hole, mainly in the marginal area of the OT and in the retina. However, all of the irradiated embryos hatched normally without apparent histological abnormalities in their brains.
  
  
  CONCLUSIONS
  Our present study indicates that the medaka embryo is a useful model for evaluating neurocytotoxic effects on the developing CNS induced by exposure to heavy iron-ions relevant to the aerospace radiation environment.
authors.affiliation: Department of Integrated Biosciences, Graduate School of Frontier Sciences, the University of Tokyo, Kashiwa, Chiba. t_yasuda@ib.k.u-tokyo.ac.jp
authors.forename: Takako
authors.initials: T
authors.lastname: Yasuda
authors.forename: Shoji
authors.initials: S
authors.lastname: Oda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yasuda
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Hibi
authors.forename: Kazunori
authors.initials: K
authors.lastname: Anzai
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mitani
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D001921:Brain / Q000166:cytology / Q000196:embryology* / Q000528:radiation effects*; D003603:Cytotoxins / Q000633:toxicity*; D004625:Embryo, Nonmammalian / Q000528:radiation effects*; D020450:Heavy Ions / Q000009:adverse effects*; D007501:Iron / Q000633:toxicity*; D023421:Models, Animal; D009990:Oryzias / Q000196:embryology*; D012062:Relative Biological Effectiveness
chemical_list: D003603:Cytotoxins; D007501:Iron