Title: Genomic Studies of Health Effects Following the Chernobyl Accident: Lessons Learned and Public Health Implications
Abstract: The talk will address two parallel studies using genomics to investigate important questions in radiation-related issues following the Chernobyl accident in 1986. In the first study, we report a large-scale integrated genomic landscape analysis of PTCs after the Chernobyl accident with detailed dose estimation points to DNA double-strand breaks as early carcinogenic events. Here, for the first time, the genomic landscape could eb carefully analyzed in relation to a specific, discrete environmental exposure of ionizing radiation, a known Class 1 IARC carcinogen. We observed that a parsimony of events subsequently enabled PTC growth after environmental radiation exposure. Based on detailed sequence analyses, non-homologous end-joining was consistently implicated as the key repair mechanism for the observed radiation dose-associated clonal DNA double-strand breaks, leading to more fusion drivers, small deletions, and structural variants as a result of increasing radiation dose. Tumor epigenomic and transcriptomic profiles reflected the PTC driver but were not associated with radiation dose. Because other mutagens can cause DNA double-strand breaks, a unique biomarker for radiation-induced carcinogenesis was not identified. Linear increases in radiation-associated damage, especially for exposure at younger ages, emphasize the potential deleterious consequences of ionizing radiation exposure.
The second study looked at the effects of radiation exposure from the Chernobyl nuclear accident which remain a topic of interest. We investigated whether children born to parents employed as cleanup workers or exposed to occupational and environmental ionizing radiation after the accident were born with more germline de novo mutations (DNMs). Whole-genome sequencing of 130 children (born 1987–2002) and their parents did not reveal an increase in the rates, distributions, or types of DNMs relative to the results of previous studies. We find no elevation in total DNMs, regardless of cumulative preconception gonadal paternal [mean = 365 milligrays (mGy), range = 0 to 4080 mGy] or maternal (mean = 19 mGy, range = 0 to 50 mGy) exposure to ionizing radiation. Thus, over this exposure range, evidence is lacking for a substantial effect on germline DNMs in humans, suggesting minimal impact from transgenerational genetic effects.
