Mitochondrial DNA mutations in individuals occupationally exposed to ionizing radiation

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Wilding, CS ; Cadwell, K ; Tawn, EJ ; Relton, CL ; Taylor, GA ; Chinnery, PF ; Turnbull, DM

Mutations in a 443-bp amplicon of the hypervariable region HVR1 of the D-loop of mitochondrial DNA (mtDNA) were quantified in DNA extracted from peripheral blood samples of 10 retired radiation workers who had accumulated external radiation doses of .0.9 Sv over the course of their working life and were compared to the levels of mutations in 10 control individuals matched for age and smoking status. The mutation rate in the 10 exposed individuals was 9.92 3 1025 mutations/ nucleotide, and for the controls it was 8.65 3 1025 mutations/ nucleotide, with a procedural error rate of 2.65 3 1025 mutations/ nucleotide. No increase in mtDNA mutations due to radiation exposure was detectable (P 5 0.640). In contrast, chromosomal translocation frequencies, a validated radiobiological technique for retrospective dosimetric purposes, were significantly elevated in the exposed individuals. This suggests that mutations identified through sequencing of mtDNA in peripheral blood lymphocytes do not represent a promising genetic marker of DNA damage after low-dose or low-doserate exposures to ionizing radiation. There was an increase in singleton mutations above that attributable to procedural error in both exposed and control groups that is likely to reflect age-related somatic mutation.
  • References (38)
    38 references, page 1 of 4

    1. R. W. Taylor and D. M. Turnbull, Mitochondrial DNA mutations in human disease. Nat. Rev. Genet. 6, 389-402 (2005).

    2. D. C. Wallace, J. M. Shoffner, I. Trounce, M. D. Brown, S. W. Ballinger, M. Corral-Debrinski, T. Horton, A. S. Jun and M. T. Lott, Mitochondrial DNA mutations in human degenerative diseases and aging. Biochim. Biophys. Acta 1271, 141-151 (1995).

    3. P. F. Chinnery, N. Howell, R. M. Andrews and D. M. Turnbull, Clinical mitochondrial genetics. J. Med. Genet. 36, 425-436 (1999).

    4. P. F. Chinnery, Modulating heteroplasmy. Trends Genet. 18, 173-176 (2002).

    5. C. Richter, J. W. Park and B. N. Ames, Normal oxidative damage to mitochondrial and nuclear DNA is extensive. Proc. Natl. Acad. Sci. USA 85, 6465-6467 (1988).

    6. L. A. Marcelino and W. G. Thilly, Mitochondrial mutagenesis in human cells and tissues. Mutat. Res. 434, 177-203 (1999).

    7. A. Chomyn and G. Attardi, MtDNA mutations in aging and apoptosis. Biochem. Biophys. Res. Commun. 304, 519-529 (2003).

    8. A. May and V. A. Bohr, Gene-specific repair of gamma-ray-induced DNA strand breaks in colon cancer cells: No coupling to transcription and no removal from the mitochondrial genome. Biochem. Biophys. Res. Commun. 269, 433-437 (2000).

    9. G. Singh, W. W. Hauswirth, W. E. Ross and A. H. Neims, A method for assessing damage to mitochondrial DNA caused by radiation and epichlorohydrin. Mol. Pharmacol. 27, 167-170 (1985).

    10. S. Prithivirajsingh, M. D. Story, S. A. Bergh, F. B. Geara, K. K. Ang, S. M. Ismail, C. W. Stevens, T. A. Buchholz and W. A. Brock, Accumulation of the common mitochondrial DNA deletion induced by ionizing radiation. FEBS Lett. 571, 227-232 (2004).

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