In two major studies, researchers used cutting-edge genomic tools to investigate the potential health effects of exposure to ionizing radiation, a known carcinogen, from 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 genetic changes in the tumors of people who developed thyroid cancer after being exposed, children or fetuses, to radiation released by the accident.
The findings, published around the 35th anniversary of the disaster, come from international teams of researchers led by researchers from the National Cancer Institute (NCI), which is part of the National Institutes of Health. The studies were 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 by the nuclear accident that followed the tsunami in Fukushima, Japan said Stephen J. Chanock, MD, director of the Division of Epidemiology and Cancer Genetics (DCEG) at NCI. “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 resulting from 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 have been affected by the disaster.
The first study examined the long-standing question of whether radiation exposure causes genetic changes that can be passed from parent to offspring, as has been suggested by some animal studies. 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 had helped clean up after the accident or had been evacuated because they lived near the accident site. Each parent was assessed for prolonged exposure to ionizing radiation, which may have occurred as a result of consuming contaminated milk (i.e. milk from cows that grazed on pastures contaminated with radioactive fallout) . Mothers and fathers suffered a range of doses of radiation.
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 at random in a person’s gametes (sperm and eggs) and can be passed on to their offspring but are not seen in 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 parents. 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 resulting from the accident had little or no impact on the health of the next generation.
“We consider these results to be very reassuring for the people who were living in Fukushima at the time of the 2011 accident,” said Dr Chanock. “We know that radiation doses in Japan were 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 in childhood or in utero to ionizing radiation from radioactive iodine ( I-131) released by the Chernobyl nuclear accident and in 81 unexposed people born more than nine months after the accident. One of the most significant adverse health effects observed after the accident was the increased risk of thyroid cancer.
Energy from ionizing radiation breaks 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 exposed children at younger ages.
Next, the researchers identified the candidate cancer “drivers” in each tumor – the key genes in which alterations allowed cancers to grow and survive. They identified the drivers in over 95% of the tumors. Almost all of the alterations involved genes in the same signaling pathway, called the mitogen-activated protein kinase (MAPK) pathway, including the BRAF, RAS, and RET genes.
The set of affected genes is similar to what has been reported in previous thyroid cancer studies. However, the researchers observed a shift in the distribution of types of mutations in genes. Specifically, in the Chernobyl study, thyroid cancers that occurred in people exposed to higher doses of radiation while children were more likely to result from genetic fusions (when both strands of DNA are broken and that the bad bits are then put together), while those from unexposed people or those exposed to low levels of radiation were more likely to result from point mutations (changes of a single base pair in a key part of a uncomfortable).
The results suggest that double-stranded DNA breaks may be an early genetic change after exposure to radiation in the environment that subsequently allows the growth of thyroid cancers. Their findings provide a basis for further studies of radiation-induced cancers, particularly those involving risk differences based on both dose and age, the researchers added.
“An exciting aspect of this research has been the opportunity to link the 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 the Radiation Epidemiology Directorate of the DCEG, who led the study.
“The Cancer Genome Atlas has set the standard for how to comprehensively profile tumor characteristics,” continued Dr. Morton. “We extended this approach to complete the first major study of the genomic landscape in which potential carcinogenic exposure was well characterized, which allowed us to investigate the relationship between specific tumor characteristics and radiation dose.”
She noted that the study was made possible by the establishment 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. ‘hui.
“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,” said Dr Morton. “The tissue bank was created by visionary scientists to collect tumor samples from residents of highly contaminated areas who developed thyroid cancer. These scientists recognized that there would be substantial technological advancements in the future. , and the research community now benefits from their foresight. “