Preferential induction of RET/PTC1 rearrangement by X-ray irradiation
Preferential induction of RET/PTC1 rearrangement by X-ray irradiation
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DOI：
10.1038/sj.onc.1203343
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发表时间：
2000-01-20
期刊：
影响因子：
8
通讯作者：
Hamatani, K
中科院分区：
文献类型：
--
作者：
Mizuno, T;Iwamoto, KS;Hamatani, K
电离辐射是甲状腺癌发生的一个众所周知的危险因素，但辐射致癌的机制尚不清楚。RET/PTC癌基因是RET原癌基因的一种活化形式，在甲状腺乳头状癌（PTC）中经常观察到; RET/PTC 1、-2和-3已知是三种主要形式。在放射相关PTC中观察到高频率的RET/PTC重排，例如切尔诺贝利或放射治疗后出现的重排，但重排类型在这两个人群之间不同。我们研究了是否一种特定类型的RET/PTC重排诱导的X射线在体内和体外。在scid小鼠移植的人正常甲状腺组织中，在50戈伊X射线照射后60天内，RET/PTC 1重排占优势，而RET/PTC 3仅在照射后7天才检测到，未检测到RET/PTC 2的转录本。这些结果得到了体外研究结果的支持，在高剂量范围（10、50和100戈伊）内的X射线在4种细胞系中以剂量依赖性方式优先诱导RET/PTC 1重排。另一方面，RET/PTC 3以低得多的频率诱导，并且未观察到RET/PTC 2的诱导。这些结果表明，RET/PTC 1重排的优先诱导可能发挥了重要作用，在甲状腺癌的早期步骤，由急性X射线照射诱导。
Ionizing radiation is a well known risk factor of thyroid cancer development, but the mechanism of radiation induced carcinogenesis is not clear. The RET/PTC oncogene, an activated form of the RET proto-oncogene, is frequently observed in papillary thyroid carcinoma (PTC); RET/PTC1, -2 and -3 are known to be the three major forms, High frequencies of RET/PTC rearrangements have been observed in radiation-associated PTC, such as those appearing post-Chernobyl or post-radiotherapy, but the rearrangement types differ between these two populations. We investigated whether a specific type of RET/PTC rearrangement was induced by X-rays in vivo and in vitro. ln human normal thyroid tissues transplanted in scid mice, the RET/PTC1 rearrangement was predominantly detected throughout the observation period (up to 60 days) after X-ray exposure of 50 Gy, On the other hand, RET/PTC3 was detected only 7 days after X-irradiation, and no transcript of RET/PTC2 was detected. These results are supported by the results of an in vitro study, The RET/PTC1 rearrangement was preferentially induced in a dose-dependent manner by X-rays within a high dose range (10, 50 and 100 Gy) in four cell lines. On the other hand, RET/PTC3 was induced at a much lower frequency, and no induction of RET/PTC2 was observed. These results suggest that the preferential induction of the RET/PTC1 rearrangement may play an important role in the early steps of thyroid carcinogenesis induced by acute X-irradiation.