Low dose X-radiation adaptive response in spleen and prostate of Atm knockout heterozygous mice.
OBJECTIVE
To investigate the effect of being heterozygous for a knockout mutation in the ataxia telangiectasia (Atm) gene on radiation adaptive response.


METHODS
DNA recombination, as measured by pKZ1 inversion frequency, was quantified by histochemistry in Atm knockout heterozygous prostate and spleen 3 days after treatment with a priming dose of 0.01 or 10 mGy X-radiation 4 h prior to a challenge dose of 1,000 mGy.


RESULTS
In spleen and prostate, a single dose of 0.01 mGy caused an induction in inversion frequency but a dose of 10 mGy prevented the induction of a proportion of endogenous inversions. Both doses induced an adaptive response, of similar magnitude, to a subsequent high challenge dose for chromosomal inversions in both spleen and prostate. The adaptive response completely prevented the induction of inversions from a 1,000 mGy challenge dose and also a proportion of endogenous inversions. The adaptive responses and distribution of inversions across gland cross-sections observed here in Atm knockout heterozygote prostate were similar to those induced in Atm wild-type prostate in a previous study.


CONCLUSIONS
Being heterozygous for a knockout mutation in the Atm gene does not affect the endogenous pKZ1 inversion frequency, the inversion response to single low radiation doses used here, or the induction of a radiation adaptive response for inversions in pKZ1 mouse spleen or prostate.
Day
Tanya K
TK
Department of Haematology and Genetic Pathology, Flinders University and Medical Centre, Bedford Park, South Australia, Australia.
Hooker
Antony M
AM
Zeng
Guoxin
G
Sykes
Pamela J
PJ
D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000528:radiation effects*; D007446:Chromosome Inversion / Q000528:radiation effects*; D004268:DNA-Binding Proteins / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D006579:Heterozygote; D006651:Histocytochemistry; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011467:Prostate / Q000502:physiology / Q000528:radiation effects*; D017346:Protein Serine-Threonine Kinases / Q000528:radiation effects*; D011836:Radiation Tolerance / Q000502:physiology / Q000528:radiation effects*; D011995:Recombination, Genetic; D013154:Spleen / Q000502:physiology / Q000528:radiation effects*; D013997:Time Factors; D025521:Tumor Suppressor Proteins / Q000528:radiation effects*; D014965:X-Rays
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse; D017346:Protein Serine-Threonine Kinases