The Characterization and Transmissibility of Chromosome Aberrations Induced in Peripheral Blood Lymphocytes byIn Vitroα-Particle Radiation

Abstract

Peripheral blood lymphocytes were irradiated in vitro with (213)Bi alpha particles at doses of 0, 10, 20, 50, 100, 200 and 500 mGy. Chromosome analysis was performed on 47-h cultures using single-color fluorescence in situ hybridization (FISH) to paint chromosomes 1, 3 and 5. The whole genome was analyzed for unstable aberrations to derive aberration frequencies and determine cell stability. The dose response for dicentrics was 33.60 +/- 0.47 x 10(-2) per Gy. A more detailed analysis revealed that the majority of aberrations scored as dicentrics were part of complex/multiple aberrations, with the proportion of cells containing complexes increasing with dose. Cells containing aberrations involving painted chromosomes (FISH aberrations) were further classified according to cell stability and complexity. The majority of cells with FISH aberrations were unstable. The proportion of aberrant FISH cells with complex/multiple aberrations ranged from 56% at 10 mGy to 89% at 500 mGy. A linear dose response for genomic frequencies of translocations in stable cells fitted the data from 0 to 200 mGy with a dose response of 7.90 +/- 0.98 x 10(-2) per Gy, thus indicating that they are likely to be observed in peripheral blood lymphocytes from individuals with past or chronic exposure to high-LET radiation. Comparisons with the dose response for low-LET radiation suggest an RBE of 13.6 for dicentrics in all cells and 3.2 for translocations in stable cells. Since stochastic effects of radiation are attributable to genetic changes in viable cells, translocations in stable cells may be a better measure when considering the comparative risks of different qualities of radiation.

Chromosome aberrations in workers with exposure to α-particle radiation from internal deposits of plutonium: expectations from in vitro studies and comparisons with workers with predominantly external γ-radiation exposure

“…This is an established aberration profile for cumulative in vivo external low dose, low dose rate, cumulative c-ray exposure as radiation-induced aberrant cells will usually contain just one single simple aberration (Tawn et al, in preparation). In vitro studies have demonstrated that the most likely outcome of a single nuclear traversal by an aparticle is a complex aberration involving multiple breaks in multiple chromosomes (Anderson et al 2002(Anderson et al , 2005Tawn et al 2007;Curwen et al 2012). However, the vast majority of the cells containing such damage will be unstable and eliminated during subsequent cell divisions, and it is the cells with the less frequently induced simple translocations that survive.…”

“…In vitro studies on the induction of chromosome aberrations by a-particle radiation have revealed the complexity of the damage (Anderson et al 2000;Moquet et al 2001;Anderson et al 2002Anderson et al , 2003Barquinero et al 2004;Anderson et al 2007;Tawn et al 2007Tawn et al , 2008Curwen et al 2012). A densely ionizing a-particle will only intersect a small fraction of the cell volume and the deposition of energy and resulting DNA damage will be localized along the particle track, resulting in multiple rearrangements.…”

“…A densely ionizing a-particle will only intersect a small fraction of the cell volume and the deposition of energy and resulting DNA damage will be localized along the particle track, resulting in multiple rearrangements. The complexity of these rearrangements is such that the vast majority will be unstable and hence incapable of successful cell division (Anderson et al 2000(Anderson et al , 2003Tawn et al 2007;Curwen et al 2012). The profile of chromosome damage seen in peripheral blood lymphocytes of nuclear workers with internally deposited plutonium will therefore only represent a small fraction of the chromosomally aberrant cells that arose from exposure of precursor cells to plutonium deposited in the bone marrow or on bone surfaces.…”

“…However, more detailed analyses revealed that most insertions and inversions were part of complex unstable aberrations, and therefore very few would be transmissible (Barquinero et al 2004;Tawn et al 2007Tawn et al , 2008Curwen et al 2012). Nevertheless, the application of multi-coloured FISH (mFISH) has shown that, whilst the majority of aparticle-irradiated cells will suffer complex non-transmissible chromosome damage, a significant proportion survive with simple exchanges, in particular translocations, that can be passed on to descendant cells (Anderson et al 2005;Curwen et al 2012).…”

Fifth Warren K. Sinclair Keynote Address: Issues in Quantifying the Effects of Low-Level Radiation

“…The low viability of human lymphocytes that contain complex aberrations has been shown experimentally by Anderson et al (2003). Tawn et al (2007) recently found that the RBE for induction of stable translocations by exposure to 213 Bi alpha particles, relative to the doselinear term of low-LET gamma rays, was only three, whereas the RBE for initial induction of dicentrics was 14. The low probability for hemopoietic cells, including stem cells, to survive the passage of a single alpha particle (Lorimore et al 1993;Griffiths et al 1994) may be the main explanation for the observed RBE for human leukemia apparently being much lower than the w R of 20 specified for alpha particles in radiation protection.…”