Delayed Effects of Radiation on Mitochondrial DNA in Radiation-Sensitive Organs

Since Balb/c mice are sensitive to acute hematopoietic syndrome and C57BL/6 to late fibrovascular toxicity, we measured the effect of total body irradiation (TBI) on mitochondrial DNA (mtDNA) copy number in these two strains. Six months after TBI, we extracted total genomic DNA, including nuclear DNA (nDNA) and mtDNA, from various tissues. The findings included: (1) TBI had no significant effect on body weight for Balb/c or C57BL/6 when compared to aged controls. (2) For different organs in control mice, the ratio of mtDNA to nDNA ranged from 0.33 to 11.53 in Balb/c and 0.34 to 13.28 in C57BL/6. (3) Ratios of mtDNA to nDNA were generally similar to or higher in C57BL/6 compared to Balb/c. (4) In C57BL/6, TBI induced an increase in mitochondrial copy number only in the brain (p < 0.05). (5) In Balb/c, radiation induced a dose-dependent increase of mtDNA in the liver (p < 0.05 and p < 0.01) and a decrease in skeletal/muscle tissue (p < 0.01). Our findings indicate that radiation influences mtDNA copy number differently in various tissues. This may explain differences in late radiation toxicity to those organs and differences in radiation tolerance between murine strains.