Low dose irradiation of thyroid cells reveals a unique transcriptomic and epigenetic signature in RET/PTC-positive cells
Low dose irradiation of thyroid cells reveals a unique transcriptomic and epigenetic signature in RET/PTC-positive cells
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DOI：
10.1016/j.mrfmmm.2011.10.006
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发表时间：
2012-03-01
影响因子：
2.3
通讯作者：
Baatout, Sarah
中科院分区：
文献类型：
--
作者：
Abou-El-Ardat, Khalil;Monsieurs, Pieter;Baatout, Sarah
切尔诺贝利事件以及对广岛和长崎的原子弹轰炸之后所受到的高剂量辐射与居住在该地点附近的儿童甲状腺癌发病率增加有关。然而，所收集的关于低剂量辐射对甲状腺影响的数据仍然有限。我们检测了具有RET/PTC 1易位的甲状腺乳头状癌来源的TPC-1人细胞系培养物对不同剂量（0.0625、0.5和4戈伊）X射线的全基因组转录反应，并将其与具有RET/PTC 3易位的甲状腺的反应以及使用Affytron微阵列对相同剂量照射的野生型小鼠甲状腺的反应进行比较。我们发现在4戈伊的高剂量下，RET/PTC阳性系统有相当大的重叠，但在62.5 m戈伊下没有共同的基因。此外，所有剂量下RET/PTC阳性系统的反应与野生型甲状腺的反应不同，两种系统的信号传导途径不同。对TPC-1细胞中microRNA的响应的分析揭示了除了剂量响应性microRNA之外，microRNA的辐射响应性特征。我们的研究结果表明，低剂量的X射线似乎对正常甲状腺有显着的增殖作用。这一观察结果应进一步研究，而不是其对RET/PTC阳性甲状腺的影响，这是微妙的，抗增殖和系统依赖性。(C)2011 Elsevier By. All rights reserved.
The high doses of radiation received in the wake of the Chernobyl incident and the atomic bombing of Hiroshima and Nagasaki have been linked to the increased appearance of thyroid cancer in the children living in the vicinity of the site. However, the data gathered on the effect of low doses of radiation on the thyroid remain limited. We have examined the genome wide transcriptional response of a culture of TPC-1 human cell line of papillary thyroid carcinoma origin with a RET/PTC1 translocation to various doses (0.0625, 0.5, and 4 Gy) of X-rays and compared it to response of thyroids with a RET/PTC3 translocation and against wild-type mouse thyroids irradiated with the same doses using Affymetrix microarrays. We have found considerable overlap at a high dose of 4 Gy in both RET/PTC-positive systems but no common genes at 62.5 mGy. In addition, the response of RET/PTC-positive system at all doses was distinct from the response of wild-type thyroids with both systems signaling down different pathways. Analysis of the response of microRNAs in TPC-1 cells revealed a radiation-responsive signature of microRNAs in addition to dose-responsive microRNAs. Our results point to the fact that a low dose of X-rays seems to have a significant proliferative effect on normal thyroids. This observation should be studied further as opposed to its effect on RET/PTC-positive thyroids which was subtle, anti-proliferative and system-dependent. (C) 2011 Elsevier By. All rights reserved.