Radiation biology. Radioecology
ISSN: 0869-8031

Archives → 2020 → V. 60. № 1. → pp. 5-11

Article

Study of Mitochondrial DNA Copy Number and Heteroplasmy in Different Rat Brain Regions after Cranial Irradiation of Protons

S. A. Abdullaeva, E. V. Evdokimovskiia, A. I. Gazieva

Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Russia

Abstract

The studies accumulated over recent years indicate that mitochondria are the most important target of radiation damage, along with the nucleus. The structural and functional disturbances induced by radiation inthese organelles influence the post-radiation development of a whole complex of effects at the level of cellsand the whole organism of animals and humans. This study is dedicated to determining changes in the numberof copies of mitochondrial DNA (mtDNA), relative to nuclear DNA (nDNA), and identifying mutantcopies of mtDNA in three brain regions (in the hippocampus, cortex and cerebellum) of rats, at different times after irradiating their heads with protons. Real-time PCR, and method based on cleavage of mtDNA PCR products heteroduplexes by Surveyor nuclease were used in this study. Our findings show that after radiation exposure the level of mtDNA copy number in three brain regions of rats dramatically elevated with simultaneously increased level of mutant mtDNA copies. MtDNA synthesis and the level of mutant mtDNA copies are different in the hippocampus, cortex and cerebellum of rat brain after cranial exposure to protons. The results suggest that increased in the number of mutant mtDNA copies may lead to mitochondrial dysfunction with increased oxidative stress, leading to nuclear genome instability in brain regions and be associated with the development of delayed effects of ionizing radiation.

Keywords

brain regions, mtDNA copies, mtDNA mutagenesis, protons, rats