Persistence of translocation frequencies in blood lymphocytes following radiotherapy: implications for retrospective radiation biodosimetry

Abstract

Chromosome aberration analysis using a G-banding technique was performed on peripheral blood lymphocyte cultures from eight individuals over a 5 year period following therapeutic radiation exposure. Samples were placed in three time periods comprising 0-12, 12-36 and 36-60 months post-treatment. The group was heterogeneous with respect to exposure and this resulted in wide differences in initial total translocation yields. Total translocation frequencies declined in seven of the eight cases, reaching significance in four cases. This decline was attributed to a decrease in cells, which in addition to translocations, also contained aberrations such as dicentrics which resulted in them being unstable. In all eight cases, when only stable cells were considered, no significant differences were observed in translocation frequencies between the different time periods post-treatment. Thus, although the frequency of translocations in stable cells is persistent over time, extrapolating to total initial yield, and using this to equate to dose, is not possible in cases where the exposure has been high and non-homogeneous. In practice, retrospective biological dosimetry is more often required in cases of historical, usually protracted, exposures which will have been essentially uniform and not of a sufficiently high dose for many cells to have acquired more than one aberration. In such cases the frequency of translocations observed some years after the exposure can be assumed to reflect induced frequencies and be used for dose estimation.

International study of factors affecting human chromosome translocations

“…Genotoxic agents, including chemicals and ionizing radiation, induce chromosomal aberrations including translocations. Because translocations frequently persist through mitosis so that the affected cells and their progeny remain viable, they are of interest as a biomarker because they allow for meaningful assessment many years after the putative exposure has occurred [5][6][7][8][9]. Increased frequencies of stable and unstable chromosome aberrations are known to occur after radiation exposure and to increase with age.…”

Chromosome analysis in childhood cancer survivors and their offspring—No evidence for radiotherapy-induced persistent genomic instability

“…In reporting this earlier work, we neglected to mention that G-banding analysis results obtained several years after exposure from all cases but one indicated persistent and significantly raised frequencies of translocations, suggesting that the bone marrow irradiation was not inconsequential. Some of these cases have been the subject of a subsequent report [38]. A further study of radiation workers with internal deposits of plutonium and raised frequencies of translocations in peripheral blood lymphocytes also failed to detect any evidence of the induction of persistent chromosomal instability [21].…”

Eight-year follow-up study of three individuals accidentally exposed to 60Co radiation: Chromosome aberration and micronucleus analysis

“…Most retrospective dosimetry has been performed on individuals exposed to low-LET radiation [18][19][20]. The translocation frequencies have been shown to Table 3 Changes in the translocation frequency in victims accidentally exposed to 60 Co radiation.…”