The study on genomic instability initiated by radiation signature using the chromosome transfer techniue

为了解电离辐射诱导染色体不稳定性的机制，我们采用微细胞介导的染色体转移技术研究了辐射间接作用诱导的染色体不稳定性。用X射线（4、6、15戈伊）照射含有人4号或11号染色体的小鼠A9细胞，并通过微细胞融合将照射的人染色体转移到未照射的小鼠m5S细胞中。用荧光原位杂交（FISH）检测了转移的人染色体的稳定性。结果表明，在某些微细胞杂种中，受辐照的染色体本身比未受辐照的染色体不稳定。此外，通过微细胞融合将未照射的人转移到4 Gy照射的小鼠m5S细胞中。结果表明，未辐照的人染色体不稳定，在某些微细胞杂种中，辐照的小鼠染色体与未辐照的人染色体相互作用。这些结果表明，辐射染色体具有不稳定的性质，可在许多细胞分裂中传递。此外，染色体分析端粒荧光原位杂交表明，端粒功能障碍介导的端粒融合参与了辐射染色体的不稳定性。因此，本研究表明辐射间接作用在诱发染色体不稳定性中的意义。

To know the mechanism for genomic instability induced by ionizing radiation, we studied chromosome instability induced by indirect action of radiation using microcell-mediated chromosome transfer. Mouse A9 cells containing a human chromosome 4 or 11 were irradiated with X-rays (4,6,15 Gy), and the irradiated human chromosome was transferred into unirradiated mouse m5S cells by microcell fusion. The stability of the transferred human chromosome was examined by fluorescent in situ hybridization (FISH). The results indicated that the irradiated chromosome per se was unstable compared to the unirradiated chromosome in some microcell hybrids. In addition, an unirradiated human was transferred into 4 Gy-irradiated mouse m5S cells by microcell fusion. The results showed that the unirradiated human chromosome was unstable, interacting with the irradiated mouse chromosomes in some microcell hybrids. These results suggest that an irradiated chromosome has unstable nature that is transmissible over many cell divisions. Moreover, chromosome analysis using telomere FISH indicated that telomere fusions mediated by telomere dysfunction was involved in the instability of the irradiated chromosome. Therefore, the present study indicates the significance of indirect action of radiation in the induction of chromosome instability.