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Directional genomic hybridization: inversions as a potential biodosimeter for retrospective radiation exposure

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Abstract

Chromosome aberrations in blood lymphocytes provide a useful measure of past exposure to ionizing radiation. Despite the widespread and successful use of the dicentric assay for retrospective biodosimetry, the approach suffers substantial drawbacks, including the fact that dicentrics in circulating blood have a rather short half-life (roughly 1–2 years by most estimates). So-called symmetrical aberrations such as translocations are far more stable in that regard, but their high background frequency, which increases with age, also makes them less than ideal for biodosimetry. We developed a cytogenetic assay for potential use in retrospective biodosimetry that is based on the detection of chromosomal inversions, another symmetrical aberration whose transmissibility (stability) is also ostensibly high. Many of the well-known difficulties associated with inversion detection were circumvented through the use of directional genomic hybridization, a method of molecular cytogenetics that is less labor intensive and better able to detect small chromosomal inversions than other currently available approaches. Here, we report the dose-dependent induction of inversions following exposure to radiations with vastly different ionization densities [i.e., linear energy transfer (LET)]. Our results show a dramatic dose-dependent difference in the yields of inversions induced by low-LET gamma rays, as compared to more damaging high-LET charged particles similar to those encountered in deep space.

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Acknowledgments

Funding for this work from NASA (NNX08AB65G; NNX09CE42P; NNX10CB05C; NNJ06HA29A) and NIH/NIAID (R01AI080486-02) is gratefully acknowledged.

Conflict of interest

A conflict of interest may be perceived for FAR, EHG, JSB, SMB and MNC as they are founders and shareholders of KromaTiD Inc.

Ethical standards

The experiments reported here comply with the ethical standards for research in the United States of America.

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Authors and Affiliations

  1. Department of Environmental & Radiological Health Sciences, Colorado State University, Fort Collins, CO, 80523, USA

    F. Andrew Ray, Joel S. Bedford & Susan M. Bailey

  2. KromaTiD Inc., 320 East Vine Drive, Fort Collins, CO, 80524, USA

    Erin Robinson, Miles McKenna & Edwin H. Goodwin

  3. Universities Space Research Association, Houston, TX, 77058, USA

    Megumi Hada

  4. Wyle Science, Technology and Engineering Group, Houston, TX, 77058, USA

    Kerry George

  5. National Aeronautics and Space Administration, Houston, TX, 77058, USA

    Francis Cucinotta

  6. Department of Radiation Oncology, University of Texas Medical Branch, Galveston, TX, 77555, USA

    Michael N. Cornforth

Authors
  1. F. Andrew Ray
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  2. Erin Robinson
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  3. Miles McKenna
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  4. Megumi Hada
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  5. Kerry George
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  6. Francis Cucinotta
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  7. Edwin H. Goodwin
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  8. Joel S. Bedford
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  9. Susan M. Bailey
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  10. Michael N. Cornforth
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Correspondence to F. Andrew Ray.

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Ray, F.A., Robinson, E., McKenna, M. et al. Directional genomic hybridization: inversions as a potential biodosimeter for retrospective radiation exposure. Radiat Environ Biophys 53, 255–263 (2014). https://doi.org/10.1007/s00411-014-0513-1

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  • DOI: https://doi.org/10.1007/s00411-014-0513-1

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