Past Exposure to Densely Ionizing Radiation Leaves a Unique Permanent Signature in the Genome

Abstract

Speculation has long surrounded the question of whether past exposure to ionizing radiation leaves a unique permanent signature in the genome. Intrachromosomal rearrangements or deletions are produced much more efficiently by densely ionizing radiation than by chemical mutagens, x-rays, or endogenous aging processes. Until recently, such stable intrachromosomal aberrations have been very hard to detect, but a new chromosome band painting technique has made their detection practical. We report the detection and quantification of stable intrachromosomal aberrations in lymphocytes of healthy former nuclear-weapons workers who were exposed to plutonium many years ago. Even many years after occupational exposure, more than half the blood cells of the healthy plutonium workers contain large (>6 Mb) intrachromosomal rearrangements. The yield of these aberrations was highly correlated with plutonium dose to the bone marrow. The control groups contained very few such intrachromosomal aberrations. Quantification of this large-scale chromosomal damage in human populations exposed many years earlier will lead to new insights into the mechanisms and risks of cytogenetic damage.

Genomic instability in radiation-induced mouse lymphoma from p53 heterozygous mice

“…We conclude from this genomic analysis of mouse lymphoma that the majority of radiation-induced tumors carry a genomic imprint of radiation exposure. Interestingly, recent studies of lymphocytes from healthy former nuclear weapons workers have detected stable intrachromosomal alterations associated with radiation exposure (Hande et al, 2003). Our studies demonstrate that initial damage from radiation exposure leads to at least four categories of radiationinduced tumors, which appear to have adopted different genetic instability profiles.…”

Ionizing Radiation Induces Frequent Translocations with Delayed Replication and Condensation

“…Therefore, to determine whether the delay in mitotic chromosome condensation chromosomes in our irradiated primary blood lymphocytes represented interchromosomal translocations and to estimate the frequency of interchromosomal translocations in these irradiated populations, we analyzed mitotic spreads using FISH with five different whole chromosome painting probes. Note that this analysis does not discriminate between simple and complex translocations, nor does it detect intrachromosomal rearrangements, which are also quite common after exposure to ionizing radiation (10). We anticipated that the frequency that any given chromosome would display the delay in mitotic chromosome condensation phenotype would be proportional to its size.…”

Clinical implications of radiation-induced genomic instability

“…All of the patients were also exposed to numerous chemical mutagens simultaneously. The plutonium exposed population showed a markedly increased rate of intrachromosomal rearrangements that seems to suggest that very densely ionizing radiation may produce a unique and durable signature in the genome (Hande et al, 2003). Future work with the mBAND technique may extend upon this demonstration of stable intrachromosomal aberrations to discover evidence of genomic instability.…”