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

俄罗斯玛雅克工人和日本胸透患者肝癌和肺癌的分子流行病学分析

• 批准号: 15406010
• 负责人: FUKUMOTO Manabu
• 金额: $ 3.9万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-15406010/
• 关键词: radiation carcinogenesis; Plutonium; Thorotrast; internal exposure; human; angiosarcoma; mesothelioma; α-particles; 肝

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

Thorotrast（Th）是一种含有天然α粒子发射体ThO_2的放射性造影剂，在第二次世界大战期间使用。注射后Thorotrast主要沉积在肝脏，慢性暴露诱发肝脏恶性肿瘤。Thorotrast患者中血管肉瘤（AS）的相对风险很高，肝内胆管癌（CCC）的发生率也很高。苏联Mayak钚厂的α粒子作业工人也发生了肝硬化和CCC。Mayak病例的病理标本保存在南乌拉尔生物物理研究所。Th和Pu诱导的肝肿瘤的分子机制的分析使得阐明人类辐射致癌机制成为可能。在该基金支持的实验期间，我们访问了俄罗斯两次，并在德国讨论了一次。考虑到SUBI对外界的人是封闭的，我们的成功是直接与他们见面， ...更多信息 艾德病理标本是划时代的。我们首先试图分析Mayak病例的遗传变化，但由于其储存条件而失败。因此，我们通过暴露超过6个月的放射自显影来确认α粒子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则未见。Th在AS和CCC肝组织切片上均有明显表达，CCC组Th径迹数高于AS组。在MYAKAS中，α径迹从实质细胞和白细胞发射。目前正在对α-径迹和肝脏结构重塑进行定量，以阐明它们之间的关系。在238例Th诱发的间皮瘤中发现3例Th外渗诱发的间皮瘤。在SUBI期间，我们发现了7例恶性间皮瘤，并将其病理组织块带回日本。我们还在日本收集石棉引起的间皮瘤。我们正在进行SV 40病毒颗粒和生长因子的免疫组织化学分析，以阐明人类的辐射致癌作用。少

项目成果

Nakayama S, Fukumoto M et al.: "Allelotypes as potential prognostic markers in ovarian carcinoma treated with cisplatin-based chemotherapy"Int J Mol Med. 11(5). 621-625 (2003)

Nakayama S、Fukumoto M 等人：“等位基因作为基于顺铂的化疗治疗卵巢癌的潜在预后标志物”Int J Mol Med。

Allelotypic characteristics of Thorotrast-induced intrahepatic chol-angiocarcinoma : comparison to non-Thorotrast-associated liver cancers.

Thorotrast 诱导的肝内胆管癌的等位基因特征：与非 Thorotrast 相关肝癌的比较。

• 发表时间: 2004
• 期刊: Radiat Res 161(2)
• 作者: Liu D;Fukumoto M et al.
• 通讯作者: Fukumoto M et al.

The involvement of polyamines as substrates of transglutaminase in zonal different hepatocyte proliferation after partial hepatectomy.

多胺作为转谷氨酰胺酶底物参与部分肝切除术后不同区域肝细胞增殖。

• 发表时间: 2005
• 期刊: Biol Pharm Bull 28(2)
• 作者: Ohtake Y;Fukumoto M et al.
• 通讯作者: Fukumoto M et al.