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 (gamma-H2AX) and alkaline Comet assays. Such remarkable transgenerational destabilization of the F(1) 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.
journal_name
Oncogenejournal_title
Oncogeneauthors
Barber RC,Hickenbotham P,Hatch T,Kelly D,Topchiy N,Almeida GM,Jones GD,Johnson GE,Parry JM,Rothkamm K,Dubrova YEdoi
10.1038/sj.onc.1209723subject
Has Abstractpub_date
2006-11-30 00:00:00pages
7336-42issue
56eissn
0950-9232issn
1476-5594pii
1209723journal_volume
25pub_type
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