Skip to main content

Mitochondrial Genetic Abnormalities After Radiation Exposure

  • Conference paper
  • First Online:
Oxygen Transport to Tissue XXXVI

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.

David Maguire deceased at the time of publication.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 229.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Campbell NA, Williamson B, Heyden RJ (2006) Biology: exploring life. Pearson Prentice Hall, Boston

    Google Scholar 

  2. Krebs HA (1970) The history of the tricarboxylic acid cycle. Perspect Biol Med 14:154–170

    Article  CAS  PubMed  Google Scholar 

  3. Kornburg HL (1987) Tricarboxylic acid cycles. Bioessays 7:236–238

    Article  Google Scholar 

  4. Watford M (1991) The urea cycle: a two-compartment system. Essays Biochem 26:49–58

    CAS  PubMed  Google Scholar 

  5. McBride HM, Neuspiel M, Wasiak S (2006) Mitochondria: more than just a powerhouse. Curr Biol 16:R551–R560

    Article  CAS  PubMed  Google Scholar 

  6. Zaider M, Bardash M, Fung A (1994) Molecular damage induced directly and indirectly by ionizing radiation in DNA. Int J Radiat Biol 66:459–465

    Article  CAS  PubMed  Google Scholar 

  7. Malakhova L, Bezlepkin VG, Antipova V et al (2005) The increase in mitochondrial DNA copy number in the tissues of gamma-irradiated mice. Cell Mol Biol Lett 10:721–732

    CAS  PubMed  Google Scholar 

  8. Zhang H, Zhang SB, Sun W et al (2009) B1 sequence-based real-time quantitative PCR: a sensitive method for direct measurement of mouse plasma DNA levels after gamma irradiation. Int J Radiat Oncol Biol Phys 74:1592–1599

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Zhang SB, Maguire D, Zhang M et al (2013) Maternal bias in mouse radiosensitivity: the role of the mitochondrial PTP. Adv Exp Med Biol 789:251–256

    Article  CAS  PubMed  Google Scholar 

  10. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25:402–408

    Article  CAS  PubMed  Google Scholar 

  11. Harman D (1972) The biologic clock: the mitochondria? J Am Geriatr Soc 20:145–147

    Article  CAS  PubMed  Google Scholar 

  12. Larsen NB, Rasmussen M, Rasmussen LJ (2005) Nuclear and mitochondrial DNA repair: similar pathways? Mitochondrion 5:89–108

    Article  CAS  PubMed  Google Scholar 

  13. Yamamori T, Yasui H, Yamazumi M et al (2012) Ionizing radiation induces mitochondrial reactive oxygen species production accompanied by upregulation of mitochondrial electron transport chain function and mitochondrial content under control of the cell cycle checkpoint. Free Radic Biol Med 53:260–270

    Article  CAS  PubMed  Google Scholar 

  14. Leach JK, Van Tuyle G, Lin PS et al (2001) Ionizing radiation-induced, mitochondria-dependent generation of reactive oxygen/nitrogen. Cancer Res 61:3894–3901

    CAS  PubMed  Google Scholar 

  15. Wen Q, Hu Y, Ji F et al (2011) Mitochondrial DNA alterations of peripheral lymphocytes in acute lymphoblastic leukemia patients undergoing total body irradiation therapy. Radiat Oncol 6:133

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Zhang SB, Zhang M, Cao Y et al (2012) Delayed effects of radiation on mitochondrial DNA in radiation-sensitive organs. Adv Exp Med Biol 737:139–145

    Article  CAS  PubMed  Google Scholar 

  17. Tang JT, Yamazaki H, Inoue T et al (1999) Mitochondrial DNA influences radiation sensitivity and induction of apoptosis in human fibroblasts. Anticancer Res 19:4959–4964

    CAS  PubMed  Google Scholar 

  18. Rogounovitch TI, Saenko VA, Shimizu-Yoshida Y et al (2002) Large deletions in mitochondrial DNA in radiation-associated human thyroid tumors. Cancer Res 62:7031–7041

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This paper was prepared in honor of the final work performed by David Maguire during his time in our laboratory shortly before his passing. We would also like to thank Kate Casey-Sawicki for expert editorial guidance and insights.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Paul Okunieff M.D. .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media, LLC

About this paper

Cite this paper

Maguire, D., Zhang, S.B., Okunieff, P. (2014). Mitochondrial Genetic Abnormalities After Radiation Exposure. In: Swartz, H.M., Harrison, D.K., Bruley, D.F. (eds) Oxygen Transport to Tissue XXXVI. Advances in Experimental Medicine and Biology, vol 812. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-0620-8_1

Download citation

Publish with us

Policies and ethics