[en] Thorotrast is a 25% colloidal solution of natural α-emitter, thorium dioxide, which was used as a radiological contrast medium during World War II. Decades after injection, it caused hepatic tumors by local exposure to α-particles. The epidemiological study was performed independently by two groups: National Institute of Radiological Sciences and Aichi Cancer Center, Japan. In total, they enrolled 412 cases for the study and collected paraffin embedded blocks from 392 cases. We have accumulated as many blocks as possible and, re-embedded in paraffin and put them in order with the unified numbering along with autopsy records. Histological examination of the liver was carried out on 131 male and 13 female cases. They mainly consisted of intrahepatic carcinoma (ICC) (25.7%), angiosarcoma (20.8%) and hepatocellular carcinoma (HCC) (14.6%). Any type of tumors was not induced in 33.3% of cases. In order to elucidate carcinogenic mechanisms in radiation-induced cancers, we analyzed mutations of the p53 and the K-ras genes, microsatellite instability (MSI) and loss of heterozygosity (LOH) in Thorotrast-induced ICC. Furthermore, we analyzed microdistribution of Thorium deposited in the liver using an imaging plate system. Using PCR techniques, more than 83% of cases in paraffin-embedded sections were applicable for these studies as long as the size of PCR products was less than 200 bp. Major mutations of the p53 gene were transition type. The frequency of MSI in Thorotrast-induced ICC was significantly higher than ICC without Thorotrast. MSI was partly attributed to inactivation of the hMLH1 promoter via hyermethylation. LOH profile revealed that Thorotrast-induced ICC was inbetween HCC and ICC. This is consistent with the fact that histological diagnosis is difficult in some cases of Thorotrast-induced liver cancers. Using the imaging plate technique, we could quantify the deposited amount of thorium. In addition, we could calculate the total deposited amount in the organ from a pathological section. We emphasize that archival materials from Thorotrast cases are valuable for the assessment of relevance of long-term exposure to low dose α-particles to radiation carcinogenesis. (author)