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Journal of Environmental Pathology, Toxicology and Oncology

ISSN for PRINT: 0731-8898

Institutional price:	$672.00
Issues per year:	4

Best Paper Award Selection - Editorial Board Site

2001, Volume20

98 pages

Issue price - $160.00

Alpha-Particle Carcinogenesis in Thorotrast® Patients: Epidemiology, Dosimetry, Pathology, and Molecular Analysis

Yuichi Ishikawa
Department of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research. Toshima-ku, Tokyo, Japan

Ikuo Wada
Department of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research. Toshima-ku, Tokyo, Japan

Manabu Fukumoto
Department of Pathology, Institute for Development, Aging and Cancer, Tohoku University, Sendai, Japan

ABSTRACT

We studied the alpha-radiation risks in patients who received injections of Thorotrast®, an X-ray contrast medium used in Europe, Japan, and the United States from 1930 to 1955. Thorotrast was composed of thorium dioxide (ThO₂) and Th-232, a naturally occurring radionuclide. Because the physical half-life of ThO₂ is 14 billion years and Thorotrast is hardly eliminated from the body, tissues in which it was deposited are irradiated by alpha-radiation for the entire lifetime of the subject. The dosimetry of Thorotrast patients is very complicated, but currently its reliability is quite high compared with other irradiated populations. The major causes of the death of Thorotrast patients are liver cancer, liver cirrhosis, leukemia, and other cancers. Three histologies of liver cancer are found: cholangiocarcinoma, hepatocellular carcinoma, and angiosarcoma. Although cholangiocarcinoma is the most frequent, angiosarcoma is characteristic of alpha-radiation. Among blood neoplasms with a higher incidence of increase than the general population, erythroleukemia and myelodysplastic syndrome were remarkable. Thorotrast patients exhaled a high concentration of radon (Rn-220), a progeny of Th-232, but no excesses of lung cancer in the patients of Japan, Germany, and Denmark were reported. Mutation analyses of p53 genes and loss of heterozygosity (LOH) studies at 17p locus were performed to characterize the genetic changes in Thorotrast-induced liver tumors. Interestingly, LOH, supposedly corresponding to large deletions, was not frequent; most mutations were transitions, also seen in tumors of the general population, suggesting that genetic changes of Thorotrast-induced cancers are mainly delayed mutations, and not the result of the direct effects of radiation.