Two landmark studies have harnessed the power of cutting-edge genomic tools to investigate the health effects of exposure to ionising radiation from the Chernobyl accident in 1986.
In April 1986, an accidental explosion in reactor 4 at the Chernobyl nuclear power plant in Ukraine resulted in the exposure of millions of inhabitants to radioactive contaminants. Researchers understand that exposure to ionising radiation increases DNA mutagenesis above background rates. Much of our knowledge about cancer and radiation exposure comes from such nuclear power plant accidents. Now, two new studies published in Science, have built on this foundation using next-generation DNA sequencing platforms and other genomic characterisation tools to analyse biospecimens from individuals affected by the disaster.
Researchers in the first study by Yeager et al, explored whether the effects of radiation exposure could pass from parent to offspring. Previous animal and cellular studies have suggested that high doses of ionising radiation can lead to de novo mutations in offspring, particularly through double-strand breaks. The team performed whole-genome sequencing, SNP microarray analysis and telomere length assessment on samples from 130 children from 105 mother-father pairs. They specifically examined whether the rates of germline de novo mutations were elevated in children of parents who helped clean up the accident or were evacuated because they lived in close proximity to the site.
The whole-genome sequencing data revealed no increase in the rate, distribution or type of de novo mutations in these children. In fact, the number of de novo mutations found in these children were highly similar to that of the general population. These findings suggest that exposure to ionising radiation from the accident had a minimal, if any, impact on the health of subsequent generations.
Risk of thyroid cancer
In the second study by Morton et al, researchers used next-generation sequencing to profile the genetic changes in thyroid cancers as a result of the accident. Exposure to radioactive iodine (131I) from the fallout of the disaster resulted in an increased incidence of papillary thyroid cancer (PTC) in children. The team analysed genomic, transcriptomic and epigenomic characteristics of PTCs in 359 people exposed as children or in utero to radioactive iodine, as well as 81 unexposed individuals born more than 9 months after the accident.
The researchers found that the association between double-strand breaks and radiation exposure was stronger for children exposed at a younger age. They also found candidate drivers of the cancer in each tumour, identifying drivers in more than 95% of the tumours. The team specifically found most of these alterations in the MAPK pathway. While other researchers have reported these genes previously, the team observed a shift in the distribution of the types of mutations. Those affected during the disaster harboured more gene fusions, whereas those unexposed were more likely to have point mutations. These findings suggest that double-strand breaks are early carcinogenic events that enable PTC growth following environmental radiation exposure.
Chernobyl Tissue Bank
These teams were able to conduct these studies due to the development of the Chernobyl Tissue Bank around two decades ago. The development of advanced technologies has now enabled researchers to conduct molecular studies that were not possible at the time of its development.
Dr Lindsay Morton, study lead, stated:
“The tissue bank was set up by visionary scientists to collect tumour samples from residents in highly contaminated regions who developed thyroid cancer. These scientists recognised that there would be substantial advances in technology in the future, and the research community is now benefiting from their foresight.”
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