Mitochondrial genetic abnormalities after radiation exposure.

Abstract

Because mitochondria are prone to oxidative stress, damage to their DNA might provide a record of radiation exposure. We measured the effect of gamma radiation on mitochondrial DNA (mtDNA) copy number and common deletion (mito-CD) mutations using Beas-2B and HFL-1 cells lines and C3H/HeJ mice exposed to total-body irradiation (TBI) and sub-TBI. DNA was extracted 5 days after cell irradiation or 12 months after animal exposure. We found that: (1) natural ratios of mtDNA/nDNA and mito-CD/mtDNA varied between cell lines; (2) mtDNA copy number decreased in Beas-2B and increased in HFL-1 following 2 Gy; (3) mito-CD in both cell lines increased after 2 Gy; (4) in aged mice, the natural ratios of mtDNA/nDNA varied from 0.723 to 8.146 in different tissues; (5) in kidney tissue, TBI and sub-TBI mildly increased mtDNA copy number but substantially increased mtDNA-CD; and (6) in liver tissue, TBI and sub-TBI induced a slight increase in mtDNA copy number and a larger increase in mtDNA-CD. These findings indicate that mtDNA copy number varies in time by cell type, but there is a substantial and sustained increase in mtDNA mutations that occurs to different degrees in different tissues and cells following irradiation.