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Prevalence of mitochondrial DNA mutations in radiation associated human thyroid tumors

辐射相关人类甲状腺肿瘤中线粒体 DNA 突变的发生率

基本信息

批准号：
14380256
负责人：
SAENKO Vladimir
金额：
$ 8.13万
依托单位：
Nagasaki University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

项目摘要

Molecular events underlying radiation-induced thyroid cancer are poorly understood. Therefore, elucidation of the molecular radiation signatures is one of the urgent tasks to understand pathogenesis of thyroid cancer in exposed individuals. In our investigation within the project, we evaluated general and mutational status of mitochondrial DNA(mtDNA) in the series of post-Chernobyl and control thyroid papillary cancer(PTC) to determine whether specific alterations in mtDNA can be linked to possible radiation fallout in the affected population. We focused on relative mtDNA content, prevalence and level of common deletion(CD) and large scale deletions in mtDNA.Our data demonstrate that elevated relative mtDNA content can be found in tumor tissue in most of cases of PTCs without correlation with the level of radioiodine contamination of patients' residency or with clinicopathological characteristics. Elevated level of CD was predominantly found in tumor tissue of the radiation associated group but not in sporadic PTCs, however no correlation was noted with clinicopathological parameters, radioiodine contamination and relative mtDNA content. The quantity of large scale deletions in mtDNA was elevated in most rumor tissues especially in the radiation associated group and tended to correlate with the level of radiopollutant in PTC. Most importantly, a highly significant positive correlation between the presence of large scale mtDNA deletions and relative mtDNA content was found in radiation-associated tumors.We concluded that concordant increase of both relative mtDNA level and number of mtDNA deletions may be specific to radiation associated PTC and comprise a distinctive molecular feature of radiation-associated thyroid cancer.

人们对辐射诱发甲状腺癌的分子事件知之甚少。因此，阐明分子辐射特征是了解暴露个体甲状腺癌发病机制的紧迫任务之一。在该项目的调查中，我们评估了一系列切尔诺贝利事故后和对照甲状腺乳头状癌 (PTC) 中线粒体 DNA (mtDNA) 的一般状态和突变状态，以确定 mtDNA 的特定改变是否与受影响人群中可能的辐射影响有关。我们重点关注 mtDNA 的相对 mtDNA 含量、常见缺失 (CD) 和大规模缺失的发生率和水平。我们的数据表明，在大多数 PTC 病例中，肿瘤组织中相对 mtDNA 含量升高，与患者居住地的放射性碘污染水平或临床病理特征无关。 CD水平升高主要见于放射相关组的肿瘤组织，但不存在于散发性PTC中，但与临床病理参数、放射性碘污染和相对mtDNA含量没有相关性。在大多数肿瘤组织中，尤其是在辐射相关组中，mtDNA 中大规模缺失的数量有所增加，并且往往与 PTC 中的放射性污染物水平相关。最重要的是，在辐射相关肿瘤中发现大规模 mtDNA 缺失与相对 mtDNA 含量之间存在高度显着的正相关性。我们得出结论，相对 mtDNA 水平和 mtDNA 缺失数量的一致增加可能是辐射相关 PTC 所特有的，并且构成了辐射相关甲状腺癌的独特分子特征。

项目成果

期刊论文数量（81）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

No increase of large-scale mitochondrial DNA deletions in peripheral blood cells in residents of Kazakhstan around Semipalatinsk nuclear test side.

塞米巴拉金斯克核试验周边哈萨克斯坦居民外周血细胞线粒体DNA大规模缺失没有增加。

DOI：
发表时间：
2003
期刊：
Acta Med Nagasaki 49
影响因子：
0
作者：
Namba H;et al.;V.A.Saenko et al.;TI.Rogounovitch et al.;A.Hamada et al.;V.Saenko et al.;H.Namba et al.;M.Nakashima et al.;A.Hamada et al.
通讯作者：
A.Hamada et al.

Molecular features of mitochondrial DNA in radiation-associated thyroid tumors.

放射相关甲状腺肿瘤线粒体 DNA 的分子特征。