Complex chromosome aberrations in peripheral blood lymphocytes as a potential biomarker of exposure to high-LET alpha-particles

Purpose: To determine the induct-ion and transmission, to second and third division cells, of complex: chromosome aberrations in peripheral blood lymp hocytes after exposure to high-LET alpha-particles in vitro. Materials and methods: Separated peripheral blood lymphocytes collected fro m four healthy donors were irradiated in vitro with either high-LET alpha-p articles (121 keV/mu m; 0.5 Gy) or low-LET X-rays (250 kV constant potentia l; 3 Gy). Cells were harvested in first, second and third division post-irr adiation and chromosome aberrations observed at each cell division were ana lysed by combining the techniques of FISH and DAP1/Hoechst 33258 harlequin staining. Whole chromosome probes were used for chromosomes 1, 2 and 5, tog ether with a pan-centromeric probe and the resulting chromosome 'painting' patterns were classified according to the Savage and Simpson (S & S) scheme (Savage and Simpson 1994a, Savage and Tucker 1996). Results: A greater proportion of complex chromosome aberrations was observe d, defined as involving three or more breaks in two or more chromosomes, re lative to total exchanges, after exposure to 0.5 Gy alpha-particles (mean 1 track/cell) than after the high reference dose of 3 Gy X-rays (49-56% and 20-22%, respectively). Qualitatively, alpha-particles induced chromosome ab errations of far greater complexity than those observed after X-rays. This was reflected by both the rapid reduction in the percentage of damaged cell s between first and second division indicative of cell death, and the spect rum of aberration types observed in second and third division cells post-ir radiation. Regardless of this complexity, 15% of the complexes induced by a lpha-particles at first division were potentially transmissible and by thir d division, transmissible-type complexes, specifically insertions, represen ted the predominant complex type (65%). Conclusion: Transmissible-type complexes were observed, specifically insert ions, in both second and third division cells after exposure to high-LET al pha-particles (0.5 Gy) in vitro. The authors predict these cells to be stab le and to be capable of persisting through many cell generations. Consideri ng that the induction of complex chromosome aberrations by low-LET radiatio n is strongly dependent on dose, so that they are expected to he undetectab le at environmental exposures? insertions are much more likely to be a char acteristic feature of high-LET radiation at all doses. From this the useful ness of insertions as biomarkers of past exposure to environmentally releva nt doses of high-LET alpha-particles is supported.