Hande M P, Natarajan A T
MGC Department of Radiation Genetics and Chemical Mutagenesis, Leiden University, Netherlands.
Int J Radiat Biol. 1998 Oct;74(4):441-8. doi: 10.1080/095530098141302.
To develop a mouse model for retrospective biological dosimetry, the kinetics of induction and persistence of chromosome aberrations following X-irradiation are analysed.
Female Swiss mice were whole-body exposed to 0, 0.5, 1.0, 2.0 or 3.0 Gy X-rays. Fluorescence in situ hybridization using composite DNA libraries specific for chromosomes 1, 11 and 13 was performed on metaphase chromosomes from isolated splenocytes at 0, 7, 28, 56, 112 and 224 days post irradiation to detect chromosome aberrations.
Dose-response curves for all types of aberrations observed ¿dicentrics, fragments, metacentrics (Robertsonian fusion-like configurations) and translocations¿ were well fitted by a linear quadratic model. Equal induction of dicentrics and translocations was observed immediately after irradiation for all the doses used. The frequency of dicentrics and fragments decayed exponentially with time. Genomic translocation frequency declined with time post-irradiation and reached stability during later intervals, which was strongly dose-dependent. Reciprocal translocations and incomplete exchanges (terminal translocations) were induced at almost equal frequency immediately after X-irradiation (exception 3.0 Gy) and showed different patterns of decline.
The results, on the decay of genomic translocation frequency with time after irradiation in mouse splenocytes, have implications on the use of translocations in retrospective biological dosimetry.
为建立用于回顾性生物剂量测定的小鼠模型,分析X射线照射后染色体畸变的诱导动力学和持续情况。
对雌性瑞士小鼠进行全身0、0.5、1.0、2.0或3.0 Gy X射线照射。在照射后0、7、28、56、112和224天,对分离的脾细胞中期染色体进行荧光原位杂交,使用针对1、11和13号染色体的复合DNA文库检测染色体畸变。
观察到的所有类型畸变(双着丝粒、片段、中着丝粒(罗伯逊融合样构型)和易位)的剂量反应曲线均能很好地用线性二次模型拟合。对于所有使用的剂量,照射后立即观察到双着丝粒和易位的诱导相等。双着丝粒和片段的频率随时间呈指数衰减。基因组易位频率在照射后随时间下降,并在后期达到稳定,这强烈依赖于剂量。X射线照射后立即诱导的相互易位和不完全交换(末端易位)频率几乎相等(3.0 Gy除外),并表现出不同的下降模式。
小鼠脾细胞照射后基因组易位频率随时间衰减的结果,对易位在回顾性生物剂量测定中的应用具有启示意义。