Complex chromosome aberrations persist in individuals many years after occupational exposure to densely ionizing radiation: An mFISH study

Abstract

Long-lived, sensitive, and specific biomarkers of particular mutagenic agents are much sought after and potentially have broad applications in the fields of cancer biology, epidemiology, and prevention. Many clastogens induce a spectrum of chromosome aberrations, and some of them can be exploited as biomarkers of exposure. Densely ionizing radiation, for example, alpha particle radiation (from radon or plutonium) and neutron radiation, preferentially induces complex chromosome aberrations, which can be detected by the 24-color multifluor fluorescence in situ hybridization (mFISH) technique. We report the detection and quantification of stable complex chromosome aberrations in lymphocytes of healthy former nuclear-weapons workers, who were exposed many years ago to plutonium, gamma rays, or both, at the Mayak weapons complex in Russia. We analyzed peripheral-blood lymphocytes from these individuals for the presence of persistent complex chromosome aberrations. A significantly elevated frequency of complex chromosome translocations was detected in the highly exposed plutonium workers but not in the group exposed only to high doses of gamma radiation. No such differences were found for simple chromosomal aberrations. The results suggest that stable complex chromosomal translocations represent a long-lived, quantitative, low-background biomarker of densely ionizing radiation for human populations exposed many years ago.

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

“…Clearly this peripheral blood lymphocyte has not been through many, if any, cell divisions and was perhaps irradiated directly, not as a result of plutonium in the bone marrow, but as it passed by plutonium deposited in the lymph nodes. Therefore, three of the four plutonium workers exhibited cells with multiple chromosome rearrangements, supporting suggestions that their presence can be used as indicative of exposure to aparticle radiation (Anderson et al 2000(Anderson et al , 2005Barquinero et al 2004;Hande et al 2005;Curwen et al 2012). Dicentrics were observed in three of the five men with external exposure and two of the plutonium workers (Table 3).…”

“…Support for this comes from the in vitro work on long-term cultures reported here. Nevertheless, stable cells containing multiple aberrations are induced by a-particle radiation, albeit in small numbers, and have been observed in studies of workers exposed to internally deposited plutonium (Tawn et al 1985;Whitehouse et al 1998;Anderson et al 2005;Hande et al 2005;Livingston et al 2006;Tawn et al 2006;Sotnik et al 2014). In the current study, such cells were found in three of the nine men (Table 3).…”

“…A number of studies have characterized the chromosome aberrations observed in peripheral blood lymphocytes from nuclear workers exposed to a-particle-emitting internally deposited plutonium and attempted to relate these to the cumulative internal dose to the bone marrow (Brandom et al 1979;Tawn et al 1985;Brandom et al 1990;Whitehouse et al 1998;Hande et al 2003;Mitchell et al 2004;Anderson et al 2005;Hande et al 2005;Tawn and Whitehouse 2005;Livingston et al 2006;Tawn et al 2006;Sotnik et al 2014). The majority have identified translocations as the predominant aberration but, although their frequency is greater than that expected from any associated external low LET c-ray exposure, little has been achieved in terms of using translocation frequency to quantify the response following in vivo a-particle exposure.…”

Short dysfunctional telomeres impair the repair of arsenite‐induced oxidative damage in mouse cells

“…In the mFISH technique, all 21 chromosomes (1-19, X and Y) are each painted in a different color, using combinatorial labeling, so that any interchromosomal translocations are observed as color junctions on individual chromosomes. The experimental procedure is outlined in earlier publications (Greulich et al, 2000;Hande et al, 2003;Hande et al, 2005).…”

Persistence of Genetic Damage in Lymphocytes from Former Uranium Miners

“…Copyright © 2012 S. Karger AG, Basel Of the different kinds of genetic damage used as markers for past exposure to chromosome breaking agents, socalled clastogens, some are stable and can therefore be detected even decades after exposure, whereas others are unstable and lose their detectability within a few years. To the first category belong chromosomal translocations which are either assessed with the help of chromosome banding [Awa, 1997] or after fluorescent in situ hybridization (FISH), also referred to as 'chromosome painting' [Lucas, 1997;Hande et al, 2005]. Translocations have, for instance, been found in the lymphocytes of atomic bomb survivors of Hiroshima and Nagasaki, and it has been shown that their frequency does not substantially change with time [Kodama et al, 2001].…”