Abstract
Exogenous genotoxic agents including irradiation randomly cause genetic damage on the genome and result mutations and chromosome alterations. To precisely understand the degree and character of the DNA damages by the agents, we must genome-widely analyze the genetic changes. Genomic DNA microarray technology enables to efficiently scan the whole genome and detect relatively small regions (<100kb) with deletions, amplification, and LOH. Using CGH-microarray (Agilent) and SNP-microarray, which are designed for detecting copy-number alterations and LOH, respectively, we characterize gamma-ray-inducing genetic alterations genome-widely. We irradiated human lymphoblastoid TK6 with 5Gy gamma-ray, and randomly isolated 25-survived clones (0.1% survival). Among 25 clones, 12 showed at least one chromosome alteration with >5cM in CGH- or SNP-microarray analyses. These chromosomes alterations were confirmed as deletion, amplification, translocation, or aneuploidy by Spectrum Karyotyping analysis. Deletions and amplifications were frequently observed as side-by-side on a chromosome, implying that Breakage-Fusion-Bridge cycle initiated by a DSB may contribute to generate the complicated changes. Four clones exhibited a same unreciprocal translocation with the breakpoint at chromosome 16q11.2. This breakpoint region may contain hot spot for ionizing irradiation.
