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Radiation-induced transgenerational alterations in genome stability and DNA damage

Oncogene volume 25, pages 7336–7342 (2006)Cite this article

Abstract

Mutation induction in directly exposed cells is currently regarded as the main component of the genetic risk of ionizing radiation for humans. However, recent data on the transgenerational increases in mutation rates in the offspring of irradiated parents indicate that the genetic risk could be greater than predicted previously. Here, we have analysed transgenerational changes in mutation rates and DNA damage in the germline and somatic tissues of non-exposed first-generation offspring of irradiated inbred male CBA/Ca and BALB/c mice. Mutation rates at an expanded simple tandem repeat DNA locus and a protein-coding gene (hprt) were significantly elevated in both the germline (sperm) and somatic tissues of all the offspring of irradiated males. The transgenerational changes in mutation rates were attributed to the presence of a persistent subset of endogenous DNA lesions (double- and single-strand breaks), measured by the phosphorylated form of histone H2AX (γ-H2AX) and alkaline Comet assays. Such remarkable transgenerational destabilization of the F1 genome may have important implications for cancer aetiology and genetic risk estimates. Our data also provide important clues on the still unknown mechanisms of radiation-induced genomic instability.

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Acknowledgements

This work was supported by grants from the Wellcome Trust, the European Commission and the Department of Energy (YED), Cancer Research UK and the Hope Foundation (GDDJ) and the European Union PEPFAC project (JMP).

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Authors and Affiliations

  1. Department of Genetics, University of Leicester, Leicester, Leicestershire, UK

    R C Barber, P Hickenbotham, T Hatch, D Kelly, N Topchiy & Y E Dubrova

  2. Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester, Leicestershire, UK

    G M Almeida & G D D Jones

  3. Centre for Molecular Genetics and Toxicology, University of Wales Swansea, Swansea, UK

    G E Johnson & J M Parry

  4. Gray Cancer Institute, Northwood, Middlesex, UK

    K Rothkamm

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  1. R C Barber
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  2. P Hickenbotham
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  11. Y E Dubrova
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Correspondence to Y E Dubrova.

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Barber, R., Hickenbotham, P., Hatch, T. et al. Radiation-induced transgenerational alterations in genome stability and DNA damage. Oncogene 25, 7336–7342 (2006). https://doi.org/10.1038/sj.onc.1209723

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