Induction and persistence of cytogenetic damage in mouse splenocytes following whole-body X-irradiation analysed by fluorescence in situ hybridization. IV. Dose response.
PURPOSE: To develop a mouse model for retrospective biological dosimetry, the kinetics of induction and persistence of chromosome aberrations following X-irradiation are analysed. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.