Abstract
We have recently reported a novel deletion in mitochondrial DNA (mtDNA). This deletion was induced in a cell line, HepG2 by radiation exposure. In addition, this novel deletion was detected by PCR only in the liver from patients administered with Thorotrast which emits alpha-particles. Therefore, this novel mtDNA deletion is considered to be a marker of radiation exposure. DNA base substitutions are frequently occurred in the D-loop region of mtDNA. In order to identify mutations specifically induced by radiation exposure, we analyzed the D-loop region. Whole genomic DNA separately extracted from tumor and non-tumor tissues of the liver from Thorotrast and non-Thorotrast patients was analyzed. Sequence analysis indicated that all of the mutations induced in the D-loop region associated with Thorortrast were transition type. Mitochondrial heteroplasmy of D-loop mutations was frequently observed in Thorotrast induced angiosarcoma (AS), Thorotrast induced intrahepatic cholangiocarcinoma (ICC) and non-Thorotrast-induced AS. Compared with non-tumor tissues the incidence of cases with mutations only in tumor part was higher in Thorotrast ICC than in non-Thorotrast ICC. No mutations including deletions specific to Thorotrast patients were found. These results suggest that mtDNA mutations are not induced by alpha-particles emitted from Thorotrast but are dependent on histological type of liver tumors.
