Transmissible and Nontransmissible Complex Chromosome Aberrations Characterized by Three-Color and mFISH Define a Biomarker of Exposure to High-LET α Particles

Anderson, R. M., Marsden, S. J., Paice, S. J., Bristow, A.;thE., Kadhim, M. A., Griffin, C. S. and Goodhead, D. T. Transmissible and Nontransmissible Complex Chromosome Aberrations Characterized by Three-Color and mFISH Define a Biomarker of Exposure to High-LET α Particles. Radiat. Res. 159, 40–48 (2003). Insertions have been proposed as potential stable biomarkers of chronic high-LET radiation exposure. To examine this in vitro, we irradiated human peripheral blood lymphocytes in G0 with either 50 cGy 238Pu α particles (LET 121.4 keV/μm) or 3 Gy 250 kV X rays and stimulated their long-term culture up to ∼22 population doublings postirradiation. Mitotic cells were harvested at regular intervals throughout this culture period and were assayed for chromosome aberrations using the techniques of three-color and 24-color mFISH. We observed the stable persistence of transmissible-type complex rearrangements, all involving at least one insertion. This supports the hypothesis that insertions are relevant indicators of exposure to high-LET radiation. However, one practical caveat of insertions being effective biomarkers is that their frequency is low due to the complexity and cell lethality of the majority of α-particle-induced complexes. Therefore, we propose a “profile of damage” that relies on the presence of insertions, a low frequency of stable simple reciprocal translocations (2B), and, significantly, the complexity of the damage initially induced. We suggest that the complexity of first- and second-division α-particle-induced nontransmissible complex aberrations reflects the structure of the α-particle track and as a consequence adds radiation-quality specificity to the biomarker, increasing the signal:noise ratio of the characteristic 2B:insertion ratio.