Low dose X-radiation adaptive response in spleen and prostate of Atm knockout heterozygous mice

Tanya K Day1, Antony M Hooker, Guoxin Zeng

  • 1Department of Haematology and Genetic Pathology, Flinders University and Medical Centre, Bedford Park, South Australia, Australia.

Abstract

Insights

Heterozygous mutations in the ataxia telangiectasia (Atm) gene do not impact DNA recombination or the radiation adaptive response in mouse spleen and prostate. This finding suggests Atm heterozygosity does not alter radiation-induced adaptive responses.

Area of Science:

  • Radiation biology
  • Genetics
  • Molecular biology

Background:

  • The ataxia telangiectasia (Atm) gene plays a crucial role in DNA damage response pathways.
  • Radiation adaptive response is a phenomenon where low doses of radiation can protect against subsequent higher doses.
  • Understanding the role of Atm in this response is vital for assessing risks associated with low-dose radiation exposure.

Purpose of the Study:

  • To investigate the effect of heterozygous Atm gene knockout on the radiation adaptive response.
  • To determine if Atm heterozygosity influences DNA recombination frequency after radiation exposure.

Main Methods:

  • Mice heterozygous for Atm knockout were exposed to priming doses of X-radiation (0.01 or 10 mGy) followed by a challenge dose (1,000 mGy).
  • DNA recombination was quantified by measuring pKZ1 inversion frequency in spleen and prostate tissues using histochemistry.
  • The study compared inversion frequencies in Atm knockout heterozygotes to previously established data for Atm wild-type mice.

Main Results:

  • Both low priming doses (0.01 and 10 mGy) induced an adaptive response in spleen and prostate, significantly reducing inversions from a high challenge dose.
  • The adaptive response in Atm heterozygotes was comparable in magnitude to that observed in Atm wild-type mice.
  • Atm heterozygosity did not alter the endogenous pKZ1 inversion frequency or the response to single low radiation doses.

Conclusions:

  • Heterozygous mutation in the Atm gene does not affect DNA recombination or the induction of a radiation adaptive response.
  • The findings indicate that Atm heterozygosity does not impair the cellular mechanisms responsible for radiation-induced adaptive responses.
  • These results suggest that Atm heterozygosity does not significantly alter an organism's protective response to radiation at the assessed endpoints.

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