Induced genomic instability in irradiated germ cells and in the offspring; reconciling discrepancies among the human and animal studies

Induced genomic instability in irradiated germ cells and in the offspring; reconciling discrepancies among the human and animal studies
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DOI:
10.1038/sj.onc.1207037
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发表时间:
2003-10-13
期刊:
影响因子:
8
通讯作者:
Niwa, O
Niwa, O
中科院分区:
医学1区
文献类型:
--
作者:
Niwa, O

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许多研究证实,辐射会引起全身系统的基因组不稳定。然而,研究结果并不总是相互一致的。本次审查试图解决这些差异。在人类和实验动物中的许多研究利用小卫星序列的长度变化突变作为基因组不稳定性的标志。小卫星序列经常改变它们的长度,并且通过常规Southern印迹获得的数据提供相当定性的信息,这有时难以定量地仔细检查。这是小卫星突变研究中不可避免的问题,也是人类和小鼠研究中一些冲突的根源。辐射诱导的基因组不稳定性也进行了评估,在全身实验系统中,使用其他标记,如小鼠粉红色眼睛的不稳定等位基因和特定的色素沉着位点的青鳉鱼(Oryzias latipes)。尽管存在一些矛盾,但所有这些研究都表明,受辐射的父母(特别是男性)及其所生后代的生殖细胞中会诱导基因组不稳定性。其中,基因组不稳定性的第二代辐射的父母是有限的小鼠小卫星系统,并等待在其他实验系统进一步澄清。
Many studies confirmed that radiation induces genomic instability in whole-body systems. However, the results of the studies are not always consistent with each other. Attempts are made in the present review to resolve the discrepancies. Many of the studies in human and experimental animals utilize the length change mutation of minisatellite sequences as a marker of genomic instability. Minisatellite sequences frequently change their length, and the data obtained by conventional Southern blotting give rather qualitative information, which is sometimes difficult to scrutinize quantitatively. This is the problem inevitably associated with the study of minisatellite mutations and the source of some conflicts among studies in humans and mice. Radiation induction of genomic instability has also been assessed in whole-body experimental systems, using other markers such as the mouse pink-eyed unstable allele and the specific pigmentation loci of medaka fish (Oryzias latipes). Even though there are some contradictions, all these studies have demonstrated that genomic instability is induced in the germ cells of irradiated parents, especially of males, and in offspring born to them. Among these, transmission of genomic instability to the second generation of irradiated parents is limited to the mouse minisatellite system, and awaits further clarification in other experimental systems.