This is the authors' final draft of the paper published as Oncogene, 2007, 26(32), pp.4720-4724. The definitive published version is available from http://www.nature.com/onc/journal/v26/n32/abs/1210253a.htmlThe results of a number of recent studies show that mutation rates in the offspring of irradiated parents are substantially elevated, however the effect of parental genotype on transgenerational instability remains poorly understood. Here we have analysed the mutation frequency at an expanded simple tandem repeat (ESTR) locus in the germline and bone marrow of the first generation male offspring of control and irradiated male mice. The frequency of ESTR mutation was studied in the offspring of two reciprocal matings ♂scid x ♀BALB/c and ♂BALB/c x ♀scid, which were compared with that in BALB/c mice. In the offspring of the BALB/c x BALB/c and ♂scid x ♀BALB/c matings, which were conceived after paternal sperm irradiation, the frequency of ESTR mutation was significantly elevated in both tissues. In contrast, ESTR mutation frequency was only slightly elevated in the offspring of ♂BALB/c x ♀scid mating conceived after paternal irradiation. The results of this study suggest that the oocytes of scid females are unable to fully support the repair of double-strand breaks induced in paternal sperm which may in turn result in the elimination of cells/embryos containing high levels of DNA damage, thus partially preventing the manifestation of genomic instability
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