Elevated Mitochondrial DNA Copy Number and POL-γ Expression but Decreased Expression of TFAM in Murine Intestine Following Therapeutic Dose Irradiation

  • Hengshan ZhangEmail author
  • David J. Maguire
  • Mei Zhang
  • Lurong Zhang
  • Paul Okunieff
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 701)


Mitochondria play pivotal roles in cellular handling of oxygen and in apoptosis, the ordered suicide response of cells to irradiation. The involvement of expression products from the 16.5 kb human mitochondrial genome in these activities has been studied widely. However, little is known about effects of irradiation on mammalian mitochondrial DNA (mtDNA). The relative lack of mtDNA repair mechanisms compared with nuclear DNA (nDNA) predicts particular vulnerability to irradiation. Using a technique developed to ascertain mtDNA:nDNA ratios, we previously showed that this ratio increases dramatically inmurine small bowel within 48 hours followingwhole body irradiation. We now report that those levels continue to rise for four days and remain elevated at close to that level beyond 30 days after 5 Gy of irradiation.We further demonstrate that levels of the mtDNA-specific DNA polymerase-γ (Pol-γ ) also show a sharp and sustained increase during this time course after a 2-Gy dose. Paradoxically, transcription factor A (TFAM), exhibited the directly opposite response.


Mitochondrial Genome Human Mitochondrial Genome Biosearch Technology Murine Intestine Vibra Cell Sonicator 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Purkayastha SJ, Milligan R, and Bernhard WA (2007) On the chemical yield of base lesions, strand breaks, and clustered damage generated in plasmid DNA by the direct effect of x rays. Radiat Res 168:357-366PubMedCrossRefGoogle Scholar
  2. 2.
    Yakes FM, and Van Houten B (1997)Mitochondrial DNAdamage ismore extensive and persists longer than nuclear DNA damage in human cells following oxidative stress. Proc Natl Acad Sci USA 94:514-519PubMedCrossRefGoogle Scholar
  3. 3.
    Iliakis G, Wang H, Perrault AR, et al. (2004) Mechanisms of DNA double strand break repair and chromosome aberration formation. Cytogenet Genome Res 104:14-20PubMedCrossRefGoogle Scholar
  4. 4.
    Larsen NB, Rasmussen M, and Rasmussen LJ (2005) Nuclear and mitochondrial DNA repair: similar pathways? Mitochondrion 5:89-108PubMedCrossRefGoogle Scholar
  5. 5.
    Malakhova L, Bezlepkin VG, Antipova V, et al. (2005) The increase inmitochondrial DNAcopy number in the tissues of γ -irradiated mice. Cell Mol Biol Lett 10:721–732PubMedGoogle Scholar
  6. 6.
    ZhangH,Maguire D, Swarts S, et al. (2009) Replication ofmurinemitochondrialDNAfollowing irradiation. Adv Exp Med Biol 645:43-48CrossRefGoogle Scholar
  7. 7.
    Pfaffl MW (2001) A new mathematical model for relative quantification in real time RT-PCR. Nuc Acids Res 29:e45CrossRefGoogle Scholar
  8. 8.
    Laemmli, UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680-685PubMedCrossRefGoogle Scholar
  9. 9.
    Denham JW, Hauer-Jensen M, Kron T, et al. (2000) Treatment-time-dependence models of early and delayed radiation injury in rat small intestine. Int J Radiat Biol Phys 48:871-887CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Hengshan Zhang
    • 1
    Email author
  • David J. Maguire
    • 2
  • Mei Zhang
    • 3
  • Lurong Zhang
    • 3
  • Paul Okunieff
    • 3
  1. 1.Department of Radiation OncologyUniversity of FloridaGainesvilleUSA
  2. 2.Department of Radiation OncologyUniversity of Rochester Medical CenterRochesterUSA
  3. 3.Department of Molecular Genetics and MicrobiologyDuke University Medical CenterDurhamUSA

Personalised recommendations