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

Thorotrast （Th）是一种放射造影剂，含有天然α-粒子发射器ThO_2，在第二次世界大战期间使用。注射后，胸腔造影剂主要沉积于肝脏，长期暴露于α-颗粒诱发肝脏恶性肿瘤。血管肉瘤（AS）的相对危险度较高，肝内胆管癌（CCC）的发生频率也较高。苏联马亚克钚（Pu）生产厂α-颗粒暴露的工人也出现肝脏AS和CCC。Mayak病例的病理标本保存在南乌拉尔生物物理研究所（SUBI）。对Th和pu诱导的肝脏肿瘤分子机制的分析，使阐明辐射对人体的致癌机制成为可能。在该基金资助的实验期内，我们两次访问俄罗斯，一次在德国进行讨论。考虑到SUBI对外不对外开放，我们成功地与他们直接见面并借用了更多的病理标本，这是划时代的。我们最初试图分析玛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个月以上的放射自显影来确认α-颗粒在组织学切片上的分布。巨噬细胞中几乎全部可见沉积的Th，而未见Pu。在肝脏组织的AS和CCC切片上都发现了这种现象，而且CCC组的〓轨数比AS组高。在MYAKAS中，α-轨道从实质细胞和白细胞发出。α-轨道和肝脏结构重塑的量化正在进行中，以阐明它们之间的关系。我们在238例Th诱导肿瘤中发现3例Th外渗诱导的间皮瘤。在SUBI期间，我们发现了7例恶性间皮瘤，并将其病理阻滞带回日本。我们也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。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