Hatch T, Derijck A A H A, Black P D, van der Heijden G W, de Boer P, Dubrova Y E
Department of Genetics, University of Leicester, Leicester, UK.
Oncogene. 2007 Jul 12;26(32):4720-4. doi: 10.1038/sj.onc.1210253. Epub 2007 Jan 29.
The 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 male symbol scid x female symbol BALB/c and male symbol BALB/c x female symbol scid, which were compared with that in BALB/c mice. In the offspring of the BALB/c x BALB/c and male symbol scid x female symbol 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 male symbol BALB/c x female symbol 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.
最近一些研究的结果表明，受辐射亲本的后代中的突变率大幅升高，然而，亲本基因型对跨代不稳定性的影响仍知之甚少。在这里，我们分析了对照雄性小鼠和受辐射雄性小鼠的第一代雄性后代的生殖系和骨髓中一个扩展简单串联重复序列（ESTR）位点的突变频率。在两个相互交配的组合（雄性 scid×雌性 BALB/c 和雄性 BALB/c×雌性 scid）的后代中研究了 ESTR 突变频率，并与 BALB/c 小鼠的进行比较。在父本精子受辐射后受孕的 BALB/c×BALB/c 和雄性 scid×雌性 BALB/c 交配的后代中，两个组织中的 ESTR 突变频率均显著升高。相比之下，在父本受辐射后受孕的雄性 BALB/c×雌性 scid 交配的后代中，ESTR 突变频率仅略有升高。这项研究的结果表明，scid 雌性的卵母细胞无法完全支持修复父本精子中诱导产生的双链断裂，这可能反过来导致含有高水平 DNA 损伤的细胞/胚胎被清除，从而部分地防止了基因组不稳定性的表现。
