Radiation-induced changes in peripheral blood-derived mitochondrial DNA copy number and heteroplasmy in mice: Potential biomarkers of radiation exposure

Radiological and nuclear accidents require reliable biomarkers for rapid detection of radiation exposure and dose estimation. While conventional biodosimetry has focused on nuclear DNA damage in lymphocytes, mitochondrial DNA (mtDNA) may provide an additional index because of its high copy number and limited repair capacity. Previous studies using Epstein-Barr virus-transformed lymphocytes and HeLa-FUCCI cells demonstrated radiation-induced changes in mtDNA copy number (mtDNAcn), suggesting compensatory replication as a characteristic response, but in vivo evidence has been limited. In this study, we analyzed peripheral blood from C57BL/6N male mice (8 weeks old) exposed to 0, 0.05, 0.2, 0.5, or 2 Gy of X-rays. MtDNAcn and intact copy ratio, defined as the proportion of undamaged copies, were quantified at 1 day and 1 week post-irradiation. We found that mtDNAcn was significantly increased only in the 2 Gy group at both 1 day and 1 week, whereas the intact copy ratio was significantly decreased in the 0.5 Gy and 2 Gy groups at 1 day but returned to baseline by 1 week. These findings indicate that peripheral blood-derived mtDNA indices are promising biomarkers for radiation biodosimetry, and that intact copy ratio may be particularly useful for detecting low-dose exposure.