Long-term effects of ionizing radiation on gene expression in a zebrafish model

• Published in: PloS one Vol. 8; no. 7; p. e69445
• Main Authors: Jaafar, Lahcen, Podolsky, Robert H, Dynan, William S
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 30.07.2013; Public Library of Science (PLoS)
• Subjects: Adults; Aging; Animals; Apoptosis; Apoptosis - genetics; Apoptosis - radiation effects; BASIC BIOLOGICAL SCIENCES; Bioinformatics; Biological effects; Biology; Cancer; CCAAT/enhancer-binding protein; Cluster Analysis; Danio rerio; DNA microarrays; Drug dosages; Embryos; Exposure; Female; Fertilization; Gamma radiation; Gamma rays; Gene expression; Gene Expression Profiling; Gene Expression Regulation - radiation effects; gene regulation; Genes; Genomes; Gerontology; Growth factors; Hypoxia; In vivo methods and tests; Inflammation; Ionizing radiation; Laboratory animals; Liver; Long-term effects; Male; Medicine; microarrays; Multivariate analysis; p53 Protein; Radiation; Radiation dosage; Radiation effects; Radiation injuries; Radiation, Ionizing; radiobiology; Regulators; Reproducibility of Results; Signal Transduction - radiation effects; Statistical analysis; Time Factors; Transcription factors; transcriptional control; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; Zebrafish; Zebrafish - genetics; Zebrafish - metabolism; γ Radiation; Atlanta Georgia; United States > US; Georgia
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0069445

Understanding how initial radiation injury translates into long-term effects is an important problem in radiation biology. Here, we define a set of changes in the transcription profile that are associated with the long-term response to radiation exposure. The study was performed in vivo using zebrafish, an established radiobiological model organism. To study the long-term response, 24 hour post-fertilization embryos were exposed to 0.1 Gy (low dose) or 1.0 Gy (moderate dose) of whole-body gamma radiation and allowed to develop for 16 weeks. Liver mRNA profiles were then analyzed using the Affymetrix microarray platform, with validation by quantitative PCR. As a basis for comparison, 16-week old adults were exposed at the same doses and analyzed after 4 hours. Statistical analysis was performed in a way to minimize the effects of multiple comparisons. The responses to these two treatment regimes differed greatly: 360 probe sets were associated primarily with the long-term response, whereas a different 2062 probe sets were associated primarily with the response when adults of the same age were irradiated 4 hours before exposure. Surprisingly, a ten-fold difference in radiation dose (0.1 versus 1.0 Gy) had little effect. Analysis at the gene and pathway level indicated that the long-term response includes the induction of cytokine and inflammatory regulators and transcription and growth factors. The acute response includes the induction of p53 target genes and modulation of the hypoxia-induced transcription factor-C/EBP axis. Results help define genes and pathways affected in the long-term, low and moderate dose radiation response and differentiate them from those affected in an acute response in the same tissue.