Unusually large complex exchanges in human lymphocytes exposed to 56Fe ions

Full text: The formation of chromosome exchanges requires the interaction of breaks located in close spatial and temporal proximity. Radiations that differ markedly in ionization density and/or track structure might therefore be expected to alter the frequency of chromosome aberrations, particularly complex exchanges, which require the interaction of three or more chromosome breaks. In this study, we irradiated unstimulated (G0) human lymphocytes with accelerated 500 MeV/nucleon Fe ions (200 keV/μm) and used mFISH to study the frequency (and extent) of complex chromosome exchanges at the first postirradiation mitosis following stimulation with PHA. Results were compared to that observed following irradiation with γ-rays. Fe ions produced a whopping 18-fold increase in the frequency of complex chromosome-type exchanges over that observed in γ-irradiated cells given the same dose. Moreover, the extent of complexity of such exchanges, in terms of number of breakpoints involved, was also higher. An example is the formation of one particular exchange that presumably required the participation of 27 breaks, i.e., 54 broken chromosome ends. Fe ions also produced a number of bizarre complex exchanges that seem to defy conventional cytogenetic classification. They appear to represent true hybrid 'chromosome-chromatid-type' damage interactions, as opposed to chromatid-isochromatid interactions commonly seen following exposure during S or G2 phases of the cell cycle. Implications of these results will be discussed in terms of a possible role for complex aberrations in the assessment of prior exposure to HZE particles. This research was supported by the Office of Science (BER), U.S. Department of Energy, Grant No. DE-FG03-02ER63442 and the National Aeronautical and Space Administration Office of Biological and Physical Research (NASA/OBPR)