Urushibara Ayumi, Kodama Seiji, Yokoya Akinari
Advanced Research Science Centre, Japan Atomic Energy Agency, 2-4 Shirakata-Shirane, Tokai-mura, Ibaraki, Ibaraki 319-1195, Japan; Laboratory of Radiation Biology, Department of Biological Science, Graduate School of Science, Osaka Prefecture University, 1-2 Gakuen-cho, Nakaku, Sakai, Osaka 599-8570, Japan.
Laboratory of Radiation Biology, Department of Biological Science, Graduate School of Science, Osaka Prefecture University, 1-2 Gakuen-cho, Nakaku, Sakai, Osaka 599-8570, Japan.
Mutat Res Genet Toxicol Environ Mutagen. 2014 May 15;766:29-34. doi: 10.1016/j.mrgentox.2014.02.005. Epub 2014 Mar 15.
Exposure of cells to ultraviolet (UV)-A radiation induces oxidative damage in DNA, such as 8-oxo-7,8-dihydroguanine (8-oxoG), single-strand breaks, a-basic sites, and DNA-protein cross-links, via reactions with reactive oxygen species (ROS). In this study we examine whether the damage other than double-strand breaks (non-DSB damage), which is UV-A-induced oxidative damage, plays a role in the induction of chromosomal instability. We exposed human chromosome 21 to UV-A and transferred the chromosome into non-irradiated mouse recipient cells by microcell-mediated chromosome transfer. The chromosomal instability of both the transferred human chromosome and the recipient mouse chromosomes was examined by whole-chromosome painting and fluorescence in situ hybridization (WCP-FISH). The ploidy of the mouse recipient cells increased, and chromosomal aberrations occurred not only in the UV-A-irradiated human chromosome but also in the non-irradiated mouse chromosomes. The frequencies of these abnormalities increased with the radiation dose received by the transferred human chromosome. In contrast, in the control experiment, in which an non-irradiated human chromosome was transferred, the micro-cell hybrids remained diploid, and the frequency of chromosomal aberrations in both the transferred human chromosome and recipient mouse chromosomes remained low. Thus, the present study indicates that a chromosome harboring non-DSB damage induced by UV-A irradiation is unstable and transmits instability to chromosomes of non-irradiated recipient mouse cells.
细胞暴露于紫外线A（UV-A）辐射会通过与活性氧（ROS）反应，在DNA中诱导氧化损伤，如8-氧代-7,8-二氢鸟嘌呤（8-氧代G）、单链断裂、α-碱性位点和DNA-蛋白质交联。在本研究中，我们检测了UV-A诱导的氧化损伤中除双链断裂以外的损伤（非双链断裂损伤）是否在染色体不稳定性的诱导中起作用。我们将人类21号染色体暴露于UV-A，然后通过微细胞介导的染色体转移将该染色体转入未受辐射的小鼠受体细胞中。通过全染色体涂染和荧光原位杂交（WCP-FISH）检测转移的人类染色体和受体小鼠染色体的染色体不稳定性。小鼠受体细胞的倍性增加，染色体畸变不仅出现在受UV-A辐射的人类染色体中，也出现在未受辐射的小鼠染色体中。这些异常的频率随着转移的人类染色体所接受的辐射剂量增加而增加。相比之下，在对照实验中，转入未受辐射的人类染色体时，微细胞杂种保持二倍体，并且转移的人类染色体和受体小鼠染色体中的染色体畸变频率均保持较低水平。因此，本研究表明，携带由UV-A辐射诱导的非双链断裂损伤的染色体是不稳定的，并将不稳定性传递给未受辐射的受体小鼠细胞的染色体。
