Analysis of chromosome aberrations by FISH and Giemsa assays in lymphocytes of cancer patients undergoing whole-body irradiation: comparison of in vivo and in vitro irradiation

Purpose : To study the cytogenetic effects of fractionated radiotherapy in peripheral blood lymphocytes of five cancer patients. In vitro experiments were performed in parallel using the same dose range and a comparison was m ade of the induced frequencies of stable and unstable chromosome aberration s. The object was to clarify the use of an in vitro calibration curve for i mmediate and retrospective dosimetry in cases of radiation accidents. Materials and methods : Patients were exposed to Co-60 gamma -rays at a sin gle dose of 11.5 cGy each day up to a total dose of 57.5 cGy, given in 5 da ys. For measurement of chromosome aberrations, blood was collected from pat ients before irradiation and after each exposure. Blood taken before treatm ent was used as a control and for in vitro irradiation experiments in the d ose range 8-50 cGy. Chromosome aberration frequency (stable as well as unst able) was determined using fluorescence in situ hybridization (FISH) assay with specific DNA libraries for chromosomes 1, 4 and 8 and a pancentromerti c probe for the whole genome. Giemsa-stained preparations were used to scor e unstable aberrations following in vivo and in vitro exposure. Results: A linear dose-response curve was determined for both dicentrics an d translocations. The in vivo frequency of translocations was higher than f or dicentrics. Dose-response curves generated for translocations following in vivo and in vitro irradiation yielded similar frequencies. In contrast, for dicentrics, in vitro irradiation yielded a higher frequency when compar ed with data generated following in vivo exposure. Conclusions : For dose r econstruction purposes, translocations frequency seems to be a more adequat e end-point than the scoring of dicentrics. The established in vitro calibr ation curve for dicentrics may underestimate absorbed radiation dose in cas es of protracted exposure.