Cancers induced by alpha particles from Thorotrast

Abstract To investigate human cancers induced by alpha-radiation, patients who had an injection of Thorotrast, a radioactive colloidal X-ray contrast medium composed of thorium dioxide (ThO 2 ) used in Europe, US and Japan during 1930–1955, have been studied. The thorotrast patients died mainly of liver cancer, liver cirrhosis, leukemia and other cancers. Among the three histologies of liver cancer (cholangiocarcinoma, hepatocellular carcinoma and angiosarcoma), angiosarcoma was visible for alpha-radiation. In increased blood neoplasms, erythroleukemia and myelodysplastic syndrome were remarkable. Thorotrast patients exhale an extremely high concentration of radon (Rn-220), typically 20,000 Bq/m 3 , but there has been no excess of lung cancer. Analyses of p53 mutations and loss-of-heterozygosity (LOH) at the 17p locus were performed to characterize the Thorotrast-induced liver tumors. Interestingly, LOH supposedly corresponding to large deletions was not frequent and most mutations were transitions, as seen in tumors of the general population. Therefore suggesting that genetic changes of Thorotrast-induced cancers are mainly “delayed mutations”, not results of direct effects of radiation.