Long-term effects of ionizing radiation on gene expression in a zebrafish model
- Authors
- Jaafar, L., Podolsky, R.H., and Dynan, W.S.
- ID
- ZDB-PUB-130903-18
- Date
- 2013
- Source
- PLoS One 8(7): e69445 (Journal)
- Registered Authors
- Keywords
- none
- Datasets
- GEO:GSE46026
- MeSH Terms
-
- Animals
- Apoptosis/genetics
- Apoptosis/radiation effects
- Cluster Analysis
- Female
- Gene Expression Profiling
- Gene Expression Regulation/radiation effects*
- Male
- Radiation, Ionizing*
- Reproducibility of Results
- Signal Transduction/radiation effects
- Time Factors
- Tumor Suppressor Protein p53/genetics
- Tumor Suppressor Protein p53/metabolism
- Zebrafish/genetics*
- Zebrafish/metabolism
- PubMed
- 23936019 Full text @ PLoS One
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.