No excess mutations in the children of Chernobyl survivors, new study finds

A Ukrainian boy holds a picture of his dead grandfather, a liquidator who helped clean up radioactive debris scattered after a nuclear reactor exploded at Chernobyl in 1986.

SERGEI SUPINSKY/AFP via Getty Images

Survivors of the Chernobyl nuclear disaster have long lived with a lingering fear: Did radiation exposure mutate their sperm and eggs, possibly dooming their children to genetic diseases? “Many people think if you have been irradiated, you must have effects in the next generation,” says immunologist Dimitry Bazyka, director-general of the National Research Centre for Radiation Medicine in Kyiv, Ukraine. But new findings from Bazyka and his colleagues should dispel that fear. In a study of more than 200 Chernobyl survivors and their children, the researchers found no evidence of a transgenerational effect.

The study largely resolves a major uncertainty surrounding health outcomes of the world’s worst nuclear accident, whose 35th anniversary takes place Monday. And it offers a reassuring message to evacuees from areas contaminated by Japan’s 2011 Fukushima nuclear accident. “There’s still a lot of nervousness in Japan and elsewhere about transgenerational effects,” says geneticist Stephen Chanock, director of the U.S. National Cancer Institute’s Division of Cancer Epidemiology and Genetics.

The explosion of the Chernobyl Nuclear Power Plant’s reactor No. 4 in Ukraine on 26 April 1986 and subsequent fire unleashed a plume of radioactive contamination over a large swath of Europe. Two plant workers died in the explosion and 28 firefighters died from acute radiation poisoning. For a multitude of others exposed to radionuclides, the effects have unfolded more gradually. Ionizing radiation breaks DNA; radioactive iodine spewed from the destroyed reactor triggered thyroid cancers in children and adolescents starting about 5 years after the accident. Other studies have linked exposures to cancers such as leukemia and to cardiovascular disease.

Worries about germline mutations have cast a long shadow. Parents typically pass 50 to 100 such mutations, appearing in the DNA of their sperm and eggs, on to their children. The only proven risk factor for a greater number of these so-called de novo mutations (DNMs) is a father’s age—the older he is, the more DNMs in his sperm. Although DNMs aren’t necessarily harmful, a handful have been associated with some forms of autism and other developmental disorders. Animal studies have heightened anxiety that radiation exposures mess with germ cells: Mice zapped with radiation, for example, have more DNMs than unexposed mice. But past studies haven’t yielded clear answers as to whether radiation inflicts lasting damage on human germline DNA.

About 8 years ago, Chanock struck up a collaboration with Bazyka and others to hunt for DNMs in radiation-exposed parents and their children. The team tracked down families in which the father had been involved in the perilous cleanup operation of the smoldering reactor ruins of Chernobyl or one or both parents had been evacuated hours after the accident from nearby settlements such as Pripyat, where power plant workers and their families lived.

The researchers had robust estimates of ionizing-radiation doses. Cleanup workers, men known as liquidators, wore dosimeters, and evacuee doses were reconstructed from environmental contamination assessments and by directly measuring the uptake of radioactive iodine by the thyroid gland. Doses in men ranged from zero to 4 grays; in women, they ranged from zero to 550 milligrays. (Five grays in a single exposure can kill.)

Working with colleagues at the Broad Institute, Chanock’s team sequenced the genomes of 105 parents and 130 children born between 1987 and 2002. Numbers of DNMs were no greater than those seen in the general population—even at the highest radiation doses, the researchers report today in Science.

“The authors have done an excellent job. Very impressive size and a very high genome coverage,” says Yuri Dubrova, a geneticist at the University of Leicester who in the 1990s and early 2000s reported elevated mutation rates, in short, repetitive DNA sequences known as minisatellites in fathers living in contaminated areas near Chernobyl. Studies of even shorter repetitive sequences, known as microsatellite DNA, have yielded mixed results. Chanock’s team found no evidence of a higher mutation rate in either sort of DNA.

Perhaps the mouse studies pointed to a transgenerational effect because, unlike the Chernobyl liquidators or evacuees, the mice were generally exposed to single intense bursts of radiation, Chanock says. Exposures occurring over hours or days could allow DNA repair mechanisms to eliminate excess mutations before they are passed along to children. Dubrova finds that explanation plausible. “They may be right,” he says. “We don’t know for how long germ cells can ‘remember’ the history of mutagenic insult.”

Next, Chanock and Bazyka hope to track down more children of liquidators born soon after the accident—in 1987 and 1988—as well as any grandchildren.

For Bazyka, the apparent lack of a transgenerational effect offers a ray of hope in what has been a long and dark saga for Ukraine—and for him. He was in Kyiv at the time of the accident, and as a medical consultant at the interior ministry, he treated police officers whom he calls “real heroes.” They enforced a safety perimeter around the reactor and suffered burns from beta particles in the radioactive dust. Ever since, Bazyka has also held a grim vigil for the liquidators, many of whom have succumbed to cancers, cardiovascular ailments, and cognitive decline. “At least,” he says, “their children should be healthier than they are.”

source: sciencemag.org