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Mitochondrial Genetic Abnormalities After Radiation Exposure

Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 812)

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.

Keywords

Mitochondrial DNA Irradiation Reactive oxygen species Common deletion Mitochondrial copy number 

Notes

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.

References

  1. 1.
    Campbell NA, Williamson B, Heyden RJ (2006) Biology: exploring life. Pearson Prentice Hall, BostonGoogle Scholar
  2. 2.
    Krebs HA (1970) The history of the tricarboxylic acid cycle. Perspect Biol Med 14:154–170CrossRefPubMedGoogle Scholar
  3. 3.
    Kornburg HL (1987) Tricarboxylic acid cycles. Bioessays 7:236–238CrossRefGoogle Scholar
  4. 4.
    Watford M (1991) The urea cycle: a two-compartment system. Essays Biochem 26:49–58PubMedGoogle Scholar
  5. 5.
    McBride HM, Neuspiel M, Wasiak S (2006) Mitochondria: more than just a powerhouse. Curr Biol 16:R551–R560CrossRefPubMedGoogle Scholar
  6. 6.
    Zaider M, Bardash M, Fung A (1994) Molecular damage induced directly and indirectly by ionizing radiation in DNA. Int J Radiat Biol 66:459–465CrossRefPubMedGoogle Scholar
  7. 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 10:721–732PubMedGoogle Scholar
  8. 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 74:1592–1599CrossRefPubMedPubMedCentralGoogle Scholar
  9. 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 789:251–256CrossRefPubMedGoogle Scholar
  10. 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 25:402–408CrossRefPubMedGoogle Scholar
  11. 11.
    Harman D (1972) The biologic clock: the mitochondria? J Am Geriatr Soc 20:145–147CrossRefPubMedGoogle Scholar
  12. 12.
    Larsen NB, Rasmussen M, Rasmussen LJ (2005) Nuclear and mitochondrial DNA repair: similar pathways? Mitochondrion 5:89–108CrossRefPubMedGoogle Scholar
  13. 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 53:260–270CrossRefPubMedGoogle Scholar
  14. 14.
    Leach JK, Van Tuyle G, Lin PS et al (2001) Ionizing radiation-induced, mitochondria-dependent generation of reactive oxygen/nitrogen. Cancer Res 61:3894–3901PubMedGoogle Scholar
  15. 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 6:133CrossRefPubMedPubMedCentralGoogle Scholar
  16. 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 737:139–145CrossRefPubMedGoogle Scholar
  17. 17.
    Tang JT, Yamazaki H, Inoue T et al (1999) Mitochondrial DNA influences radiation sensitivity and induction of apoptosis in human fibroblasts. Anticancer Res 19:4959–4964PubMedGoogle Scholar
  18. 18.
    Rogounovitch TI, Saenko VA, Shimizu-Yoshida Y et al (2002) Large deletions in mitochondrial DNA in radiation-associated human thyroid tumors. Cancer Res 62:7031–7041PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2014

Authors and Affiliations

  1. 1.Department of Radiation Oncology, College of MedicineUniversity of FloridaGainesvilleUSA

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