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1 January 2003 Transmissible and Nontransmissible Complex Chromosome Aberrations Characterized by Three-Color and mFISH Define a Biomarker of Exposure to High-LET α Particles
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Abstract

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.

Rhona M. Anderson, Samantha J. Marsden, Stephen J. Paice, Anna E. Bristow, Munira A. Kadhim, Carol S. Griffin, and Dudley T. Goodhead "Transmissible and Nontransmissible Complex Chromosome Aberrations Characterized by Three-Color and mFISH Define a Biomarker of Exposure to High-LET α Particles," Radiation Research 159(1), 40-48, (1 January 2003). https://doi.org/10.1667/0033-7587(2003)159[0040:TANCCA]2.0.CO;2
Received: 13 May 2002; Accepted: 1 September 2002; Published: 1 January 2003
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