Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
EFFECTS OF LOW-DOSE GAMMA IRRADIATION DURING EARLY LIFE STAGES IN THE ZEBRAFISH MODEL ab Selma Hurem , Hans Christian Teienac, Ole Christian Lindac, Dag Anders Bredeac, Turid Hertel-Aasac, Lene Sørlie Heierac, Vidar Bergab, Leonardo Martinab, Deborah Oughtonac, Brit Salbuac, Peter Alestrømab, Jan Ludvig Lycheab a Centre for Environmental Radioactivity (CERAD CoE), Norway b Norwegian University of Life Sciences, Vetbio, Campus Oslo, Norway c Norwegian University of Life Sciences, Department of Environmental Sciences, Campus Ås, Norway Human and zebrafish genome share 70% of the genes. The aim of this study was to assess phenotypic and genotypic changes in zebrafish embryos after exposure to low dose and chronic dose-rates of γ-radiation during two sensitive developmental stages. Zebrafish embryos AB wild type were exposed to dose-rates ranging from 0.5 to 40 mGy/h external 60Co gamma irradiation for a period of 3 hours (hpf) and 5 days post fertilization (dpf), for a total of 118 hours. Samples for gene expression analysis were collected at 5.5 hpf. Mortality, malformations, and the hatching rate were observed at 48 and 118 hpf. Total RNA for gene transcription analysis was isolated from embryos exposed between 2.5 hours and 5.5 hpf which are across the mid blastula transition and early gastrula stage of development. The quality of RNA sequenced samples was determined by photometric parameters (260/280>1.8, 260/230>2, yield>200ng/µl) and RNA integrity number (RIN>8.5) (Bioanalyzer; Agilent technologies, USA). The RNA was sequenced at BGI Tech Solutions Co., Ltd., Hong Kong. Embryo hatching rate and number of malformations were significantly different from controls in all exposure groups. Mortality observed at 5dpf was higher than in controls for all groups except for the lowest dose-rate (0.5 mGy/h). This suggests that γ-radiation in the range of 1mGy/h and higher during embryogenesis and early larval stage (equivalent to total doses of ca. 100 mGy or higher) induces acute toxic effects in zebrafish. Bioinformatic analysis of RNA-seq data showed a clear dose response relationship between the number of differentially regulated genes compared to controls, which increased with the γradiation dose. Analyzes of the gene expression data sets using Ingenuity Pathway Analysis (IPA) showed significant changes in gene networks around hnf4α (hepatocyte nuclear factor 4α) and cebpa (CCAAT/enhancer binding protein) and genes involved in eif2 signaling. Interestingly, corresponding gene transcription changes were also found in cancer patients in the post-Chernobyl period suggesting that the same mechanisms are involved in humans and zebrafish exposed to ionizing radiation.