Ionizing radiation does not impair the mechanisms controlling genetic stability during T cell receptor gene rearrangement in mice

Abstract

Purpose: To determine whether low dose/low dose rate radiation-induced genetic instability may result from radiation-induced inactivation of mechanisms induced by the ATM-dependent DNA damage response checkpoint. To this end, we analysed the faithfulness of T cell receptor (TR) gene rearrangement by V(D)J recombination in DNA from mice exposed to a single dose of X-ray or chronically exposed to low dose rate γ radiation.

Materials and methods: Genomic DNA obtained from the blood or the thymus of wild type or Ogg1-deficient mice exposed to low (0.1) or intermediate/high (0.2–1 Gy) doses of radiation either by acute X-rays exposure or protracted exposure to low dose-rate γ-radiation was used to analyse by PCR the presence of illegitimate TR gene rearrangements.

Results: Radiation exposure does not increase the onset of TR gene trans-rearrangements in irradiated mice. In mice where it happens, trans-rearrangements remain sporadic events in developing T lymphocytes.

Conclusion: We concluded that low dose/low dose rate ionizing radiation (IR) exposure does not lead to widespread inactivation of ATM-dependent mechanisms, and therefore that the mechanisms enforcing genetic stability are not impaired by IR in developing lymphocytes and lymphocyte progenitors, including BM-derived hematopoietic stem cells, in low dose/low dose rate exposed mice.

Keywords:

• low dose/low dose rate radiation
• genetic instability
• DNA damage response
• V(D)J recombination
• T cell receptor genes
• trans-rearrangements
• ATM

Acknowledgments

The authors want to thank Dr Manuel Serrano, Tumour Suppression Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain, for his gift of DNA from ATM-deficient mice tissues and Pr Joanna Polanska, Data Mining Group, Faculty of Automatic Control, Electronics, and Computer Science, Silesian University of Technology, Gliwice, Poland, for help with statistics

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work has been supported by the European Commissions (NoE DoReMi), European Atomic Energy Community`s Seventh Framework Programme [FP7/2007-2011] under grant agreement [no. 249689] and by the Research Council of Norway (RCN) through its Centres of Excellence funding scheme [223268/F50] and project no. 230306.