Analysis of loss of heterozygosity in Thorotrast-induced liver angiosarcoma

Abstract

Thorotrast (Th) is the trade name for 25% colloidal suspension of radioactive 232ThO2 that naturally emits alpha particles, and was used as a radiographic contrast agent in the World WarII. After intravascular injection, more than 50% of the total amount of Th is located in the liver and is known to induce liver angiosarcoma (AS) and cholangiocarcinma (ICC) several decades after injection. We performed genome-wide scan of loss of heterozygosity (LOH) in Th AS and compared LOH profile with that of non-Th AS and Th ICC. Over all LOH frequency was higher in Th AS than in non-Th AS but frequent LOH at 2q33, 8q23 and 20p13 was commonly obserbed. Frequent LOH at 8q and 13q was observed in Th-AS and Th-ICC. These results suggest that exposure to alpha-particles causes random genetic changes, however, crucial steps to develop tumors are histological differentiation specific but not carcinogen specific.