Molecular Epidemiological Analysis of Liver and Lung Cancers of Mayak Workers in Russia and Thorotrast Patients in Japan

Thorotrast(Th)是一种放射学造影剂，含有天然的α粒子发射体，ThO_2在第二次世界大战期间使用。注射后，Thorotrast主要沉积在肝脏，长期暴露于α-粒子可诱发肝脏恶性肿瘤。在服用Thorotrast的患者中，血管肉瘤(AS)的相对风险很高，肝内胆管细胞癌(CCC)的发生率也很高。在苏联马亚克钚生产厂接触α粒子的工人，肝脏中也出现了AS和Ccc。马亚克病例的病理标本保存在南乌拉尔生物物理研究所(SUI)。分析Th和Pu诱导的肝肿瘤的分子机制使阐明辐射对人类的致癌机制成为可能。在这项资助的实验期间，我们访问了俄罗斯两次，并在德国讨论了一次。考虑到Subi对外面的人是封闭的，我们的成功是直接与他们见面并借用…更多的病理标本是划时代的。我们首先试图分析马雅克病例的基因变化，但由于它们的储存条件而失败。因此，我们通过暴露6个月以上的时间进行放射自显影，以确认α颗粒在组织切片上的分布。几乎所有沉积的Th都在巨噬细胞中观察到，而Pu未见。Th阳性肝组织切片上均可见TH阳性，〓-Traces数在CCC型明显多于AS型。在MYAKAS中，实质细胞和白细胞发出α-Track。α-Track的定量和肝脏的结构重塑正在进行中，以澄清它们之间的关系。在238例Th诱导的肿瘤中，我们发现3例间皮瘤是由Th渗出引起的。在Subi期间，我们发现了7例恶性间皮瘤，并将其病理切片带回日本。我们还在日本收集石棉引起的间皮瘤。我们正在对SV40病毒颗粒和生长因子进行免疫组织化学分析，以阐明人类的辐射致癌作用。较少

A radiological contrast medium Thorotrast (Th) which contains a natural α-particle emitter, ThO_2 was used during World War II. After injection, Thorotrast deposited mainly in the liver and malignant liver tumors were induced by chronic exposure to α-particles. Relative risk of angiosarcoma (AS) is prominent and the frequency of intrahepatic cholangiocarcinoma (CCC) is also high in the patients with Thorotrast. The workers exposed to α-particles in plutonium (Pu) producing plant, Mayak of USSR were also suffered from AS and CCC in the liver. Pathological specimens of Mayak cases are kept in the South Ural Biophysics Institute (SUBI). Analysis of molecular mechanisms in Th- and Pu-induced liver tumors makes it possible to elucidate carcinogenic mechanisms of radiation in humans.During the experimental term supported by this grant, we visited Russia twice and discussed once in Germany. Considering that SUBI is closed to the people outside, our success to have met them directly and borrow … More ed pathological specimen was epoch-making. We first tried to analyze genetic changes in Mayak cases but failed because of their storage conditions. Therefore, we made autoradiograms by exposing more than 6 months to confirm the distribution of α-particles on the histological sections. Almost all of the deposited Th was observed in macrophages whereas Pu was not seen. Th was apparently found both on the sections of AS and CCC from Th laden liver tissues, the number of 〓-tracks was higher in CCC cases than in AS cases. In MYAKAS, α-tracks were emited from parenchymal cells and leukocytes. The quantification of α-tracks and structural remodeling of the liver is underway to clarify their relationship. We found 3 cases of mesothelioma which were induced by extravasatiion of Th out of 238 cases of Th-induced tumors. During stay in SUBI we found 7 cases of malignant mesothlioma and brought back their pathological blocks to Japan. We are also collecting Asbestos-induced mesotheliomas in Japan. We are performing immunohistochemical analysis of SV40 virus particles and growth factors to elucidate radiation carcinogenesis in humans. Less