title: The developmental toxicity and apoptosis in zebrafish eyes induced by carbon-ion irradiation.
abstract: OBJECTIVE
  Heavy ions have become potentially radiotherapeutic tools. However, studies of the effects on development of normal organs were limited. Using a zebrafish model, this study investigated the potential developmental toxicity and cell apoptosis rates in eyes exposed to carbon-ion irradiation.
  
  
  METHODS
  Zebrafish embryos at 12h post-fertilization (hpf) were irradiated using (12)C(6+) ion beams at doses of 2, 4, and 8 Gy. The reactive oxygen species (ROS) concentration was detected using the dichlorofluorescein-diacetate at 24, 48, and 72 hpf. Apoptosis was assessed by acridine orange staining at 24, 48, and 72 hpf and was also detected using the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling assay, at 72 hpf. The expression of genes governing apoptosis was examined using real-time polymerase chain reaction at 24 hpf. Eye size was measured at 144 hpf.
  
  
  RESULTS
  Ion irradiation with (12)C(6+) induced a significant increase in cell apoptosis at 24, 48 and 72 hpf. However, there was no significant increase in the ROS concentration at 24, 48, and 72 hpf. The proapoptotic genes, including P53, Bax, and Puma, were significantly upregulated. Two antiapoptotic genes, Mdm2 and Bcl-2, were significantly downregulated, and the expression levels of Capspase-9 and Caspase-3 were significantly increased. Microphthalmia was noted in the 8 Gy irradiated group.
  
  
  CONCLUSIONS
  These results suggested that carbon-ion irradiation induced apoptosis through the p53 pathway in zebrafish eyes independent of ROS generation. Irradiation at high doses may disrupt eye development of zebrafish embryos.
authors: Department of Heavy Ion Irradiation Medicine, Institute of Modern Physics, Chinese Academy of Sciences, China; Key Laboratory of Heavy Ion Irradiation Biology and Medicine of Chinese Academy of Sciences, China; Key Laboratory of Heavy Ion Irradiation Medicine of Gansu Province, China.
authors: Rong
authors: R
authors: Zhou
authors: Department of Heavy Ion Irradiation Medicine, Institute of Modern Physics, Chinese Academy of Sciences, China; Key Laboratory of Heavy Ion Irradiation Biology and Medicine of Chinese Academy of Sciences, China; Key Laboratory of Heavy Ion Irradiation Medicine of Gansu Province, China. Electronic address: zhangh@impcas.ac.cn.
authors: Hong
authors: H
authors: Zhang
authors: School/Hospital of Stomatology, Lanzhou University, China.
authors: Zhenguo
authors: Z
authors: Wang
authors: Department of Heavy Ion Irradiation Medicine, Institute of Modern Physics, Chinese Academy of Sciences, China; Key Laboratory of Heavy Ion Irradiation Biology and Medicine of Chinese Academy of Sciences, China; Key Laboratory of Heavy Ion Irradiation Medicine of Gansu Province, China.
authors: Xin
authors: X
authors: Zhou
authors: Department of Heavy Ion Irradiation Medicine, Institute of Modern Physics, Chinese Academy of Sciences, China; Key Laboratory of Heavy Ion Irradiation Biology and Medicine of Chinese Academy of Sciences, China; Key Laboratory of Heavy Ion Irradiation Medicine of Gansu Province, China.
authors: Jing
authors: J
authors: Si
authors: Department of Heavy Ion Irradiation Medicine, Institute of Modern Physics, Chinese Academy of Sciences, China; Key Laboratory of Heavy Ion Irradiation Biology and Medicine of Chinese Academy of Sciences, China; Key Laboratory of Heavy Ion Irradiation Medicine of Gansu Province, China.
authors: Lu
authors: L
authors: Gan
authors: College of Life Sciences, Northwest Normal University, China.
authors: Jianzhen
authors: J
authors: Li
authors: Department of Heavy Ion Irradiation Medicine, Institute of Modern Physics, Chinese Academy of Sciences, China; Key Laboratory of Heavy Ion Irradiation Biology and Medicine of Chinese Academy of Sciences, China; Key Laboratory of Heavy Ion Irradiation Medicine of Gansu Province, China.
authors: Yang
authors: Y
authors: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D002244:Carbon / Q000009:adverse effects*; D005123:Eye / Q000196:embryology* / Q000378:metabolism / Q000528:radiation effects* / Q000648:ultrastructure; D018507:Gene Expression Regulation, Developmental / Q000528:radiation effects; D020450:Heavy Ions / Q000009:adverse effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D002244:Carbon
keywords: Apoptosis; Carbon-ion beams; Eye development; Microphthalmia; Zebrafish