Abstract
Thorotrast was used as a radiological contrast medium during World War II. Since intravascularly administrated Thorotrast was deposited mainly in the liver and the surrounding tissues were exposed to alpha-particles emitted from Thorotrast. We are performing analysis of loss of heterozygosity (LOH) in Thorotrast-induced liver tumors among which relative risk of angiosarcoma (AS) is thought to be characteristically prominent in radiation-induced tumors. LOH frequency was higher in Thorotrast AS than in Thorotrast ICC. This suggests that direct effect of radiation contributes to the induction of AS more than ICC. In order to prove the hypothesis, we assessed common deletion (CD) of mitochondrial DNA which represents weak repair system of DNA in mitochondria. We found that CD frequency of non-tumor part was higher in Thorotrast AS and non-Thorotrast HCC compared with tumor part. In contrast, CD frequency in tumor part was higher in Thorotrast-induced intrahepatic cholangiocarcinoma and cholangiolocarcinoma compared with non-tumor part. These may result from the fact that the remodeling of non-tumor part in Thorotrast AS and non-Thorotast HCC is more dynamic and mitotic activity is less compared with their counterpart, respectively. Furthermore we found 2 novel deletions near to CD. We will discuss the meaning of these newly found deletions in relation to radiation exposures.
