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Genomic Effects of Radiation From Chernobyl Nuclear Disaster Examined in New Studies

NEW YORK — Two new genomic studies have examined the mutational effects of radiation exposure from the 1986 Chernobyl nuclear power plant accident in exposed children who developed cancers and in offspring of exposed individuals.

The explosion of reactor 4 at Chernobyl in Ukraine exposed millions of people in the surrounding region to radiation, including in Belarus and Russia. Radioactive iodine that fell on pastures further increased the risk of papillary thyroid cancer in children in the area who drank milk from cows that grazed there, raising the question whether such tumors might harbor particular radiation-linked mutational features. At the same time, there have been concerns that children born after the accident to parents who were exposed to ionizing radiation might harbor increased numbers of de novo mutations.

In a pair of studies appearing Thursday in Science, a team led by researchers at the US National Cancer Institute uncovered a dose-dependent increased risk of thyroid cancer among exposed children, though children of those exposed do not appear to have increased numbers of de novo germline mutations.

"Scientific questions about the effects of radiation on human health have been investigated since the atomic bombings of Hiroshima and Nagasaki and have been raised again by Chernobyl and by the nuclear accident that followed the tsunami in Fukushima, Japan," senior author Stephen Chanock, director of NCI's Division of Cancer Epidemiology and Genetics, said in a statement. "In recent years, advances in DNA sequencing technology have enabled us to begin to address some of the important questions, in part through comprehensive genomic analyses carried out in well-designed epidemiological studies."

For their first study, the researchers conducted a genomic, transcriptomic, and epigenetic analysis of tumor and normal thyroid tissue or blood samples from 440 individuals from Ukraine who developed papillary thyroid cancer after Chernobyl. For most of these, there was quantitative data available on the amount of I-131 to which they were exposed. They additionally analyzed 81 individuals born more than nine months after the accident.

In all, they determined the driver mutations for most of the tumors, about 95 percent, tracing them largely to members of the mitogen-activated protein kinase pathway like the genes BRAF, RAS, and RET, which have previously been implicated in thyroid tumors.

A higher radiation dose was linked to an increase in fusion mutations and mutations associated with non-homologous end-joining (NHEJ) repair, particularly among those exposed at younger ages. This suggested to the researchers that radiation damage resulting in double-stranded DNA breaks repaired by NHEJ could be an early carcinogenic event leading to papillary thyroid cancer.

The researchers were unable to uncover a unique radiation-linked pattern of mutations, though. Still, first author Lindsay Morton, a senior investigator at NCI, noted that the findings are consistent with a linear relationship between dose and double-stranded DNA breaks, as other studies have also suggested.

For their second study, the researchers sequenced the genomes of 130 children born to 105 parents between 46 weeks and 15 years after the nuclear accident. All the parents were exposed to ionizing radiation as cleanup workers or were evacuees from the region surrounding the power plant. As ionizing radiation increases DNA mutagenesis above background levels, there were concerns that children of exposed individuals might have higher-than-usual levels of de novo mutations.

However, the analysis uncovered no evidence for a link between the number of de novo mutations in these children and the radiation dose received by either their mother or their father. As a control, the researchers noted the expected ties between parental age and number of de novo mutations.

"The lack of evidence for an increase in de novo mutations was somewhat surprising — and it was also reassuring in that it provided new insights into situations in which the exposure was protracted over time," Chanock said in an email.

The researchers plan additional studies of transgenerational effects of radiation exposure, with a particular focus on the effects of a higher dose closer to conception, as well as studies into whether the radiation-dose characteristics they identified could help predict whether a specific papillary thyroid tumor was due to I-131 exposure. Morton added that they also need to examine whether radiation-related DNA double-strand breaks repaired by NHEJ have a causal role.

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