Radiation-induced transgenerational alterations in genome stability and DNA damage.

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

Oncogene

journal_title

Oncogene

authors

Barber RC,Hickenbotham P,Hatch T,Kelly D,Topchiy N,Almeida GM,Jones GD,Johnson GE,Parry JM,Rothkamm K,Dubrova YE

doi

10.1038/sj.onc.1209723

subject

Has Abstract

pub_date

2006-11-30 00:00:00

pages

7336-42

issue

56

eissn

0950-9232

issn

1476-5594

pii

1209723

journal_volume

25

pub_type

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