PUBLICATION

The developmental toxicity and apoptosis in zebrafish eyes induced by carbon-ion irradiation

Authors
Zhou, R., Zhang, H., Wang, Z., Zhou, X., Si, J., Gan, L., Li, J., Liu, Y.
ID
ZDB-PUB-150901-17
Date
2015
Source
Life sciences   139: 114-22 (Journal)
Registered Authors
Keywords
Apoptosis, Carbon-ion beams, Eye development, Microphthalmia, Zebrafish
MeSH Terms
  • Animals
  • Apoptosis/radiation effects*
  • Carbon/adverse effects*
  • Eye/embryology*
  • Eye/metabolism
  • Eye/radiation effects*
  • Eye/ultrastructure
  • Gene Expression Regulation, Developmental/radiation effects
  • Heavy Ions/adverse effects*
  • Reactive Oxygen Species/metabolism
  • Tumor Suppressor Protein p53/genetics
  • Tumor Suppressor Protein p53/metabolism
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish/metabolism
PubMed
26316448 Full text @ Life Sci.
Abstract
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.
Zebrafish embryos at 12h post-fertilization (hpf) were irradiated using (12)C(6+) ion beams at doses of 2, 4, and 8Gy. The reactive oxygen species (ROS) concentration was detected using the dichlorofluorescein-diacetate at 24, 48, and 72hpf. Apoptosis was assessed by acridine orange staining at 24, 48, and 72hpf and was also detected using the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling assay, at 72hpf. The expression of genes governing apoptosis was examined using real-time polymerase chain reaction at 24hpf. Eye size was measured at 144hpf.
Ion irradiation with (12)C(6+) induced a significant increase in cell apoptosis at 24, 48 and 72hpf. However, there was no significant increase in the ROS concentration at 24, 48, and 72hpf. 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 8Gy irradiated group.
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.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping