What 'Chornobyl dogs' can tell us about survival in contaminated environments

In the first step toward understanding how dogs -- and perhaps humans -- might adapt to intense environmental pressures such as exposure to radiation, heavy metals, or toxic chemicals, researchers atNorth Carolina State, Columbia University Mailman School of Public Health, University of South Carolina, and the National Institutes of Healthfound thattwo groups of dogs living within the Chornobyl Exclusion Zone, one at the site of the former Chornobyl reactors, and another 16.5 km away in Chornobyl City, showed significant genetic differences between them. The results indicate that these are two distinct populations that rarely interbreed. While earlier studiesfocused on the effects of the Chornobyl Nuclear Power Plant disaster on various species of wildlife, this is the firstinvestigation into the genetic structure of stray dogs living near the Chornobyl nuclear power plant.

The 1986 Chornobyl nuclear power plant disaster displaced more than 300,000 people living nearby and led to the establishment of an Exclusion Zone, a "no man's land" of an approximately 30 km radius surrounding the damaged reactor complex, While a massive steam explosion releasing enormous amounts of ionizing radiation into the air, water, and soil was the direct cause of the catastrophe, radiation exposure is not the only environmental hazard resulting from the disaster. Chemicals, toxic metals, pesticides, and organic compounds left behind by years-long cleanup efforts and from abandoned and decaying structures, including the nearby abandoned city of Pripyat and the Duga-1 military base, all contribute to an ecological and environmental disaster.

"Somehow, two small populations of dogs managed to survive in that highly toxic environment," noted Norman J. Kleiman, PhD, assistant professor of Environmental Health Sciences at Columbia Mailman School of Public Health, and a co-author. "In addition to classifying the population dynamics within these dogs at both locations, we took the first steps towards understanding how chronic exposure to multiple environmental hazards may have impacted these populations."

"The overarching question here is: does an environmental disaster of this magnitude have a genetic impact on life in the region?" says Matthew Breen, Oscar J. Fletcher Distinguished Professor of Comparative Oncology Genetics at NC State, and a corresponding author. "And we have two populations of dogs living at and near the site of a major environmental disaster that may provide key information to help us answer that question."

Earlier research by the co-authors, led by collaborators at NIH, used a much smaller set of genetic variants, but a larger number of dogs, to show that the two populations were separate and that each had complicated family structures.

In this parallel study, the team analyzed the dog DNA samples with four times the number of genetic variants, which provided a closer look at the genomes. In addition to confirming that the two populations are indeed genetically distinct, the team were also able to identify 391 outlier regions in the genomes of the dogs that differed between dogs living at the two locations. "Think of these regions as markers, or signposts, on a highway," Breen says. "They identify areas within the genome where we should look more closely at nearby genes. Moreover, some of these markers are pointing to genes associated with genetic repair; specifically, with genetic repair after exposures similar to those experienced by the dogs in Chornobyl." He went on to say "at this stage we cannot say for sure that any genetic alterations are in response to the multigenerational and complex exposures; we have a lot more work to do to determine if that is the case"

"The question we must answer now are why are there striking genetic differences between the two dog populations?" says Megan Dillion, PhD candidate at NC State and a lead author of the published study. "Are the differences just due to genetic drift, or are they due to the unique environmental stressors at each location?"

"The dog is a sentinel species," Breen says. "By and teasing out whether or not the genetic changes we detected in these dogs are the canine genome's response to the exposures the populations have faced, we may be able to understand how the dogs survived in such a hostile environment and what that might mean for any population -- animal or human -- that experiences similar exposures."

"Though 37 years have passed since the accident, the ~30-year-long half-lives of lingering radioisotopes means the danger posed by radiation exposure is still very much real," notes Kleiman, who is also director of the Columbia University Radiation Safety Officer Training course. "When radiation exposure is combined with a complex toxic chemical mixture of uncertain composition, there are very real human health concerns raised for the thousands of people who continue to work within the Exclusion Zone on continuing cleanup efforts as well as at two newly constructed nuclear fuel reprocessing plants."

Read more at Science Daily

Genetic effects of Chernobyl radiation

In two landmark studies, researchers have 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 radiation exposure to parents resulted in new genetic changes being passed 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 released by the accident.

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

"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," said Stephen J. Chanock, M.D., director of NCI's Division of Cancer Epidemiology and Genetics (DCEG). "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."

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

The first study investigated the long-standing question of whether radiation exposure results in genetic changes that can be passed from parent to offspring, as has been suggested by some studies in animals. 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 of the parents had been workers who helped clean up from the accident or had been evacuated because they lived in close proximity to the accident site. Each parent was evaluated for protracted exposure to ionizing radiation, which may have occurred through the consumption of contaminated milk (that is, milk from cows that grazed on pastures that had been contaminated by radioactive fallout). The mothers and fathers experienced 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 arise randomly in a person's gametes (sperm and eggs) and can be transmitted to their offspring but are not observed in the parents.

For the range of radiation exposures experienced by the parents in the study, there was no evidence from the 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 were highly similar to those of the general population with comparable characteristics. As a result, the findings suggest that the ionizing radiation exposure from the accident had a minimal, if any, impact on the health of the subsequent generation.

"We view these results as very reassuring for people who were living in Fukushima at the time of the accident in 2011," said Dr. Chanock. "The 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 the genetic changes in thyroid cancers that developed in 359 people exposed as children or in utero to ionizing radiation from radioactive iodine (I-131) released by the Chernobyl nuclear accident and in 81 unexposed individuals born more than nine months after the accident. Increased risk of thyroid cancer has been one of the most important adverse health effects observed after the accident.

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

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

The set of affected genes is similar to what has been reported in previous studies of thyroid cancer. However, the researchers observed a shift 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 radiation doses as children were more likely to result from gene fusions (when both strands of DNA are broken and then the wrong pieces are joined back together), whereas those in 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 results suggest that DNA double-strand breaks may be an early genetic change following exposure to radiation in the environment that subsequently enables the growth of thyroid cancers. Their findings provide a foundation for further studies of radiation-induced cancers, particularly those that involve differences in risk as a function of both dose and age, the researchers added.

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

"The Cancer Genome Atlas set the standard for how to comprehensively profile tumor characteristics," Dr. Morton continued. "We extended that approach to complete the first large genomic landscape study in which the potential carcinogenic exposure was well-characterized, enabling 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 had been developed to conduct the kind of genomic and molecular studies that are common today.

Read more at Science Daily