International research teams explore genetic effects of Chernobyl radiation

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Press release

Thursday, April 22, 2021

In two landmark studies, researchers used cutting-edge genomic tools to investigate the potential health effects of exposure to ionizing radiation, a known carcinogen, since the 1986 accident at the Chernobyl nuclear power plant in northern Ukraine. One study found no evidence that parental radiation exposure resulted in the transmission of new genetic changes from parent to child. The second study documented the genetic changes in the tumors of people who developed thyroid cancer after being exposed, as children or fetuses, to the radiation emitted by the accident.

The findings, released around the 35th anniversary of the disaster, come from international teams of investigators led by researchers from the National Cancer Institute (NCI), part of the National Institutes of Health. The studies have been published online in Science April 22.

“Scientific questions about the effects of radiation on human health have been studied since the atomic bombings of Hiroshima and Nagasaki and have been raised again by Chernobyl and the post-tsunami nuclear accident in Fukushima, Japan. “said Stephen J. Chanock, MD, director of the NCI’s Division of Cancer Epidemiology and Genetics (DCEG). “In recent years, advances in DNA sequencing technology have allowed us to begin to address some of the important questions, in part through comprehensive genomic analyzes performed in well-designed epidemiological studies.”

The Chernobyl accident exposed millions of people in the surrounding region to radioactive contaminants. Studies have provided much of the current knowledge about cancers caused by radiation exposures in nuclear power plant accidents. The new research builds on this foundation by using next-generation DNA sequencing and other genomic characterization tools to analyze biological samples from people in Ukraine who were affected by the disaster.

The first study examined the long-standing question of whether radiation exposure results in genetic changes that can be passed from parent to offspring, as some animal studies have suggested. To answer this question, Dr. Chanock and his colleagues analyzed the complete genomes of 130 people born between 1987 and 2002 and their 105 mother-father pairs.

One or both parents had been workers who helped clean up after the crash or had been evacuated because they lived near the crash site. Each parent was assessed for prolonged exposure to ionizing radiation, which may have occurred through consumption of contaminated milk (i.e., milk from cows that grazed on pasture contaminated with radioactive fallout). Mothers and fathers suffered a range of radiation doses.

The researchers analyzed the genomes of adult children for an increase in a particular type of inherited genetic change known as de novo mutations. De novo mutations are genetic changes that occur randomly in a person’s gametes (sperm and eggs) and can be passed on to their offspring but are not seen in the parents.

For the range of radiation exposures experienced by the parents in the study, there was no evidence from whole genome sequencing data of an increase in the number or types of de novo mutations in their children. born between 46 weeks and 15 years after the accident. . The number of de novo mutations observed in these children was very similar to that of the general population with comparable characteristics. As a result, the results suggest that exposure to ionizing radiation from the accident had little, if any, impact on the health of the next generation.

“We consider these findings to be very reassuring to people who were living in Fukushima at the time of the accident in 2011,” Dr Chanock said. “Radiation doses in Japan are known to have been lower than those recorded at Chernobyl.”

In the second study, researchers used next-generation sequencing to profile genetic changes in thyroid cancers that developed in 359 people exposed as children or in utero to ionizing radiation from radioactive iodine (I -131) emitted by the Chernobyl nuclear accident and in 81 unexposed people born more than nine months after the accident. The increased risk of thyroid cancer was one of the most important adverse effects observed after the accident.

Ionizing radiation energy breaks the chemical bonds in DNA, resulting in a number of different types of damage. The new study highlights the importance of a particular type of DNA damage that involves breaks in both DNA strands in thyroid tumors. The association between DNA double-strand breaks and radiation exposure was stronger in children exposed at a younger age.

Next, the researchers identified candidate cancer ‘drivers’ in each tumor – the key genes in which alterations allowed cancers to grow and survive. They identified the drivers in more than 95% of tumors. Almost all of the alterations involved genes in the same signaling pathway, called the mitogen-activated protein kinase (MAPK) pathway, including genes BRAF, RAS, and RET.

The set of genes affected is similar to what has been reported in previous thyroid cancer studies. However, the researchers observed a change in the distribution of the types of mutations in the genes. Specifically, in the Chernobyl study, thyroid cancers that occurred in people exposed to higher doses of radiation during childhood were more likely to result from genetic fusions (when both DNA strands are broken, then the bad bits come together), whereas those from unexposed people or those exposed to low levels of radiation were more likely to result from point mutations (single base pair changes in a key part of a gene ).

The findings suggest that DNA double-strand breaks may be an early genetic change following environmental radiation exposure that subsequently enables the growth of thyroid cancers. Their findings provide a basis for further studies of radiation-induced cancers, especially those that involve differences in risk depending on both dose and age, the researchers added.

“An exciting aspect of this research was the opportunity to link genomic characteristics of the tumor with information about radiation dose – the risk factor that potentially caused cancer,” said Lindsay M. Morton, Ph. D., deputy head of DCEG’s Radiation Epidemiology Branch, who led the study.

“The Cancer Genome Atlas has set the standard for how to comprehensively profile tumor characteristics,” Dr. Morton continued. “We extended this approach to complete the first large genomic landscape study in which potential carcinogenic exposure was well characterized, allowing us to investigate the relationship between specific tumor characteristics and radiation dose.”

She noted that the study was made possible by the creation of the Chernobyl Tissue Bank about two decades ago – long before the technology was developed to conduct the kind of genomic and molecular studies that are common today.

“These studies represent the first time that our group has performed molecular studies using the biological samples that were collected by our colleagues in Ukraine,” Dr. Morton said. “The tissue bank was set up by visionary scientists to collect tumor samples from residents of heavily contaminated areas who developed thyroid cancer. These scientists recognized that there would be substantial advances in technology in the future, and the research community now benefits from their foresight.

About the National Cancer Institute (NCI): The NCI leads the National Cancer Program and NIH efforts to dramatically reduce the prevalence of cancer and improve the lives of cancer patients and their families through research in cancer prevention and biology, the development of new interventions and the training and mentoring of new researchers. For more information about cancer, please visit the NCI website at cancer.gov or call the NCI contact center, the Cancer Information Service, at 1-800-4-CANCER ( 1-800-422-6237).

About the National Institutes of Health (NIH):The NIH, the country’s medical research agency, comprises 27 institutes and centers and is part of the US Department of Health and Human Services. The NIH is the primary federal agency that conducts and supports basic, clinical, and translational medical research, and studies the causes, treatments, and cures for common and rare diseases. For more information about the NIH and its programs, visit www.nih.gov.

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