Continued expression of a tissue specific activated oncogene in the early steps of radiation-induced human thyroid carcinogenesis
Continued expression of a tissue specific activated oncogene in the early steps of radiation-induced human thyroid carcinogenesis
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组织特异性激活癌基因在辐射诱发的人类甲状腺癌发生的早期阶段持续表达
DOI：
10.1038/sj.onc.1201313
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发表时间：
1997
期刊：
影响因子：
8
通讯作者：
Toshio Seyama
中科院分区：
文献类型：
--
作者：
T. Mizuno;S. Kyoizumi;Takako Suzuki;Keisuke S. Iwamoto;Toshio Seyama
电离辐射是众所周知的癌症发生的危险因素，但辐射致癌的机制尚不清楚。辐射引起的染色体重排很可能是导致恶性转化的主要遗传改变之一。与慢性粒细胞白血病（CML）相关的嵌合BCR-ABL和与甲状腺乳头状癌相关的H4-RET癌基因分别是易位和倒位的结果。体外研究表明，这些基因在细胞系中被高剂量X射线诱导。研究还表明，治疗各种儿童癌症（包括霍奇金病）的治疗性外部X射线剂量高达60戈伊，会显著增加患甲状腺癌的风险。因此，我们研究了这些嵌合基因的诱导和持久性在人甲状腺组织移植在scid小鼠后，50戈伊曝光作为一个函数的时间为2个月，以阐明甲状腺癌的早期事件。在第2天和整个2个月期间检测H4-RET基因。另一方面，在第2天检测到BCR-ABL基因，随后检测不到。这些结果表明，电离辐射导致各种癌基因激活，但只有特定的基因改变独特的甲状腺癌发生的细胞被选择性保留证明在人类甲状腺组织中的辐射致癌作用的开始的早期事件之一。
Ionizing radiation is a well-known risk factor of cancer development, but the mechanism of radiation induced carcinogenesis is not clear. Chromosomal rearrangements induced by radiation most likely are one of the principal genetic alterations resulting in malignant transformation. The chimeric BCR-ABL associated with chronic myelogenous leukemia (CML) and H4-RET oncogenes associated with thyroid papillary carcinoma are the result of a translocation and inversion, respectively. In vitro studies showed these genes were induced by high-doses of X-irradiation in cell lines. Studies also show that therapeutic external X-ray doses as high as 60 Gy for treatment of various childhood cancers including Hodgkin's disease significantly increase the risk of thyroid cancer. Therefore, we examined the induction and persistence of these chimeric genes in human thyroid tissues transplanted in scid mice after 50 Gy exposure as a function of time for 2 months to elucidate the early events of thyroid carcinogenesis. The H4-RET genes were detected on day 2 and throughout the 2 month period. On the other hand, BCR-ABL genes were detected on day 2 and were undetectable subsequently. These results suggest that ionizing radiation causes various oncogene activations, but cells with only specific gene alteration uniquely associated with thyroid carcinogenesis are selectively retained demonstrating one of the early events in the beginnings of radiation carcinogenesis in human thyroid tissues.