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.