Szeles Anna, Joussineau Sigfried, Lewensohn Rolf, Lagercrantz Svetlana, Larsson Catharina
Department of Oncology-Pathology, Karolinska University Hospital-Solna, Stockholm, Sweden.
Int J Radiat Biol. 2006 Feb;82(2):87-96. doi: 10.1080/09553000600599767.
Biological dosimetry in an acute triage situation of radiation exposure is traditionally performed by scoring unstable dicentric chromosomal aberrations after conventional Giemsa staining, and more recently also by detection of chromosomal translocations after chromosome painting by fluorescence in situ hybridization (FISH). By spectral karyotyping (SKY) each chromosome can be painted in an individual colour, permitting the scanning for structural aberrations throughout the genome in each individual metaphase. Here we have evaluated the performance of SKY analysis in a simulated triage situation after gamma irradiation.
Peripheral leukocytes were irradiated by 60Co (0 - 5 Gy) and analysed by SKY, Giemsa staining and FISH painting of chromosomes 1, 2, and 3.
At 1 Gy and higher doses, dicentric aberrations (Dic+) as well as classical one- and two-way translocations were found in increasing and dose-dependent frequencies by SKY. The frequency of dicentrics detected by Giemsa was found to be significantly higher than the total aberrations detected by SKY (p<0.001), but did not differ significantly from that of FISH painting. The difference was mainly attributable to the low sensitivity of SKY to detect Dic+ following frequent lack of acentric fragments with matching chromosomal composition.
The findings anticipate that radiation induced chromosomal aberrations may be more complex than expected from conventional and single chromosome painting analyses. While conventional Giemsa staining was found to be the method of choice for the triage situation, it is expected that extended SKY analysis will add to the knowledge of underlying mechanisms for irradiation associated chromosomal aberrations.
在急性辐射暴露分诊情况下,传统的生物剂量测定是通过常规吉姆萨染色后对不稳定双着丝粒染色体畸变进行评分来完成的,最近也通过荧光原位杂交(FISH)染色体涂染后检测染色体易位来进行。通过光谱核型分析(SKY),每条染色体都可以用单独的颜色进行涂染,从而能够在每个中期相中扫描整个基因组中的结构畸变。在此,我们评估了SKY分析在伽马辐射后的模拟分诊情况下的性能。
外周血白细胞用60Co(0 - 5 Gy)进行辐照,并通过SKY、吉姆萨染色以及对1、2和3号染色体的FISH涂染进行分析。
在1 Gy及更高剂量下,通过SKY发现双着丝粒畸变(Dic+)以及经典的单向和双向易位的频率呈增加趋势且与剂量相关。发现吉姆萨染色检测到的双着丝粒频率显著高于SKY检测到的总畸变频率(p<0.001),但与FISH涂染检测到的频率无显著差异。这种差异主要归因于SKY在检测Dic+时敏感性较低,这通常是由于缺乏具有匹配染色体组成的心形片段。
这些发现预示着辐射诱导的染色体畸变可能比传统和单染色体涂染分析预期的更为复杂。虽然发现传统吉姆萨染色是分诊情况下的首选方法,但预计扩展的SKY分析将增加对辐射相关染色体畸变潜在机制的认识。