University of Oulu

Chronic low dose ionizing radiation induces mtDNA maintenance response in chernobyl bank voles (myodes glareolus)

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Author: Itam, Prince1
Organizations: 1University of Oulu, Faculty of Science, Biology
Format: ebook
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.4 MB)
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Language: English
Published: Oulu : P. Itam, 2018
Publish Date: 2018-06-01
Thesis type: Master's thesis
Tutor: Watts, Phillip
Kesäniemi, Jenni
Reviewer: Kuittinen, Helmi
Alayon, Isidro Ojeda
The Chernobyl nuclear incident resulted in the release of high amounts of radionuclides into the environment. Subsequently the Chernobyl exclusion zone (CEZ) was established to prevent human exposure to radionuclides. An expected consequence of exposure to chronic doses of ionizing radiation (IR) in Chernobyl wildlife is increased DNA damage and oxidative stress via reactive oxygen species (ROS) production. The mitochondrial DNA (mtDNA) is the main source of endogenous ROS production, and when damaged by IR it produces more ROS and a concomitant increase in oxidative damage. The molecular mechanisms for the maintenance of the mtDNA in wildlife inhabiting the CEZ is still poorly understood. This study examined key molecular pathways responsible for mtDNA maintenance in animals (bank voles) inhabiting the CEZ (elevated and low background radiation sites). I quantified the expression of two important genes Polg2 and Sod2 implicated in mtDNA repair, replication and ROS scavenging. My model was bank vole (Myodes glareolus) liver and brain tissues sampled in contaminated areas in the CEZ and from uncontaminated control sites outside the CEZ. I also quantified variation in mtDNA copies (a proxy for numbers of mitochondria) and proportion of damaged mtDNA in bank voles. Finally, I estimated potential rate of mitochondria mutations by quantifying the frequency of heteroplasmy using whole genome sequencing (WGS) data of bank vole muscle tissue from animal from contaminated areas in the CEZ and uncontaminated control sites. There was significant upregulation of Polg2 in the livers of bank voles captured from the CEZ. Sod2 in contrast was significantly downregulated in bank voles from the CEZ. There was a non-significant increase in mtDNA copy number in bank voles inhabiting the CEZ compared to bank voles from control sites. I also observed bank voles in the CEZ contained significantly less damaged mtDNA compared with control individuals. In bank vole brains, neither Polg2 nor Sod2 expression differed among contaminated and uncontaminated sites. There were significantly elevated mitochondria copies in bank voles inhabiting the CEZ. The brain data also revealed bank voles from low radiation sites in the CEZ had significantly more damaged mtDNA compared elevated radiation sites and control areas. I found no association between level of radiation exposure and frequency of heteroplasmy, although there was some temporal differences in heteroplasmy. This result suggests that expression of mtDNA repair gene and synthesis of new genomes is a key adaptive machinery for mtDNA maintenance in response to low dose ionizing radiation. I found evidence of tissue specific differences in mtDNA damage and repair pathways in bank voles inhabiting the CEZ. However, with no increase in heteroplasmy, more studies are needed to demonstrate high mutation rates in contaminated bank voles.
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