PMID- 21770703 OWN - NLM STAT- MEDLINE DCOM- 20111021 LR - 20231104 IS - 1362-3095 (Electronic) IS - 0955-3002 (Print) IS - 0955-3002 (Linking) VI - 87 IP - 9 DP - 2011 Sep TI - Neurocytotoxic effects of iron-ions on the developing brain measured in vivo using medaka (Oryzias latipes), a vertebrate model. PG - 915-22 LID - 10.3109/09553002.2011.584944 [doi] AB - PURPOSE: 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). MATERIALS AND 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. CONCLUSION: 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. FAU - Yasuda, Takako AU - Yasuda T AD - Department of Integrated Biosciences, Graduate School of Frontier Sciences, the University of Tokyo, Kashiwa, Chiba. t_yasuda@ib.k.u-tokyo.ac.jp FAU - Oda, Shoji AU - Oda S FAU - Yasuda, Hiroshi AU - Yasuda H FAU - Hibi, Yusuke AU - Hibi Y FAU - Anzai, Kazunori AU - Anzai K FAU - Mitani, Hiroshi AU - Mitani H LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110719 PL - England TA - Int J Radiat Biol JT - International journal of radiation biology JID - 8809243 RN - 0 (Cytotoxins) RN - E1UOL152H7 (Iron) SB - IM MH - Animals MH - Apoptosis/radiation effects MH - Brain/cytology/*embryology/*radiation effects MH - Cytotoxins/*toxicity MH - Embryo, Nonmammalian/*radiation effects MH - Heavy Ions/*adverse effects MH - Iron/*toxicity MH - Models, Animal MH - Oryzias/*embryology MH - Relative Biological Effectiveness PMC - PMC3169016 EDAT- 2011/07/21 06:00 MHDA- 2011/10/22 06:00 CRDT- 2011/07/21 06:00 PHST- 2011/07/21 06:00 [entrez] PHST- 2011/07/21 06:00 [pubmed] PHST- 2011/10/22 06:00 [medline] AID - 10.3109/09553002.2011.584944 [doi] PST - ppublish SO - Int J Radiat Biol. 2011 Sep;87(9):915-22. doi: 10.3109/09553002.2011.584944. Epub 2011 Jul 19.