Long-term effects of ionizing radiation on gene expression in a zebrafish model.
Long-term effects of ionizing radiation on gene expression in a zebrafish model.
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DOI：
10.1371/journal.pone.0069445
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Dynan WS
中科院分区：
文献类型：
--
作者：
Jaafar L;Podolsky RH;Dynan WS
了解最初的辐射损伤如何转化为长期影响是辐射生物学中的一个重要问题。在这里，我们定义了一组与辐射暴露的长期反应相关的转录图谱的变化。这项研究是在体内使用斑马鱼进行的，斑马鱼是一种已建立的放射生物学模型生物。为了研究长期反应，受精后24小时的胚胎分别接受0.1Gy低剂量和1.0Gy中剂量的全身伽玛射线照射，并发育16周。然后使用Affymetrix微阵列平台分析肝脏mRNA的表达谱，并通过定量PCR进行验证。作为比较的基础，16周龄的成年人被暴露在相同剂量下，并在4小时后进行分析。进行统计分析的方式是将多次比较的影响降至最低。对这两种治疗方案的反应差异很大：360套探头主要与长期反应有关，而不同的2062套探头主要与照射前4小时照射相同年龄的成年人的反应有关。令人惊讶的是，辐射剂量相差10倍(0.1Gyvs.1.0Gy)几乎没有影响。基因和途径水平的分析表明，长期反应包括细胞因子和炎症调节因子以及转录和生长因子的诱导。急性反应包括P53靶基因的诱导和低氧诱导的转录因子-C/EBP轴的调节。结果有助于确定长期、低剂量和中等剂量辐射反应中受影响的基因和途径，并将它们与同一组织中急性反应中受影响的基因和途径区分开来。
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.
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影响因子：
2.8
作者：
Mello, Stephano S.;Fachin, Ana L.;Sakamoto-Hojo, Elza T.
通讯作者：
Sakamoto-Hojo, Elza T.
影响因子：
2.5
作者：
Bladen, Catherine L.;Navarre, Sammy;Kozlowski, David J.
通讯作者：
Kozlowski, David J.
影响因子：
5.8
作者：
Lu, Y;Liu, PY;Deng, HW
通讯作者：
Deng, HW
影响因子：
14.9
作者：
Bladen CL;Lam WK;Dynan WS;Kozlowski DJ
通讯作者：
Kozlowski DJ
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y