Radiation's long-term legacy 9/10/03. By Giles Newton Radiation can do more than increase your risk of cancer: Yuri Dubrova has found that it can also increase the risk of mutations being passed onto children.

In April 1986, an explosion ripped through reactor 4 of the Chernobyl nuclear power plant in Ukraine. It was the world's worst nuclear accident. Large parts of Ukraine, Belarus and Russia were contaminated with radiation, and a radioactive cloud spread across Europe. Breaking the news, Soviet President Mikhail Gorbachev said: "For the first time, we confront the real force of nuclear energy, out of control."

While radiation can increase the risk of human disease, such as cancer, are its effects even more insidious? Since the late 1920s, it has been known that exposure to radiation can increase the mutation rate in the germline (eggs and sperm) of organisms such as fruit flies and mice – the flies and mice then passing the mutations onto their offspring. Would the same be true in humans? This was the question Yuri Dubrova, in Moscow at the time of Chernobyl and now at the University of Leicester, set out to answer.

Fortunately for humans, germline DNA is well protected against the acquisition of mutations: most damage is repaired or, if the system realises that there is something wrong, the cell dies. "This combination makes the germline very special," says Dr Dubrova, "but it's also very difficult to study mutations. In a protein-coding gene, you might find one mutation in, say, 100 000 children."

In the late 1980s, however, Dr Dubrova heard of the pioneering work of Alec Jeffreys (now Sir Alec) on 'minisatellites'. At the University of Leicester, Professor Jeffreys had discovered long arrays of short DNA repeats. These minisatellites, which came to fame for their use in DNA fingerprinting, mutate – by gaining repeats – at a rate 1000-fold higher than a normal protein-coding gene.

"The main idea was to use these minisatellites for mutation detection," says Dr Dubrova. "If they are unstable without exposure to radiation, they might show a higher rate following exposure." Having first tested the system in mice – "I'm glad to tell you the idea worked," says Dr Dubrova; "changes in mutation rate were detectable" – he began collecting blood samples from families in Belarus, the country worst affected by Chernobyl.

In 1994, armed with the samples and with funding from the Wellcome Trust, Dr Dubrova travelled from Moscow to Leicester and, a year or so later, had shown that the mutation rate in the germline of irradiated parents was indeed higher – there was a twofold increase in the rate of mutations being passed by males through to their descendants. To check the findings, he collected samples from Ukrainians exposed to the Chernobyl radioisotopes, and from families in Kazakhstan who lived near to the Semipalatinsk nuclear test site – where the Soviet Union detonated 470 nuclear weapons between 1949 and 1989. Again, in both populations, the mutation rates in exposed families ware higher.

"All previous attempts to measure germline mutation rate in exposed families were inconclusive," says Dr Dubrova. "Our data provided the first experimental evidence that ionising radiation increases the mutation rate in the human germline."

The impact of such an increase in mutation rate on the health of the children – and perhaps of the grandchildren – of the irradiated parents is as yet unknown. The minisatellites enable the mutation rate to be measured, but have almost no clinical impact.

"With current technology, it is not yet feasible to analyse any changes in mutation rate in parts of the genome other than minisatellites. A parent's exposure to ionising radiation might increase the number of mutations passed onto a child, but the additional mutations will be scattered across the genome, and most will be harmless. A single exposure to ionizing radiation, similar to Chernobyl, should not dramatically affect the rate of illness and death in descendants. But we really don’t know."

Dr Dubrova already plans to analyse the families of Ukrainian emergency workers who went to help at Chernobyl, and families in the Techa River population, south of the Urals. The latter people lived downstream of a plant producing fuels such as plutonium and uranium. In the early 1950s, it started discharging radioactivity into local water supplies, and for many years the population downstream was exposed to an evil cocktail of strontium, caesium and plutonium, in water, fish and vegetables.

"Any human population exposed to radiation must be analysed," says Dr Dubrova. "With the technology of today, we can show only pilot data, so we must collect the resources that researchers of the future can use. With more advanced technology, they will be able to examine more subtle changes in the genome that can potentially result in clinical consequences, and then we can really find out how much radiation affects the health status of children."

Further reading

Dubrova Y E et al. (1996) Human minisatellite mutation rate after the Chernobyl accident. Nature 380: 683–6. Abstract

Dubrova Y E et al. (2002) Elevated minisatellite mutation rate in the post-Chernobyl families from Ukraine. Am J Hum Genet 71: 801–9. Abstract . Full text

Dubrova Y E et al. (2002) Nuclear weapons tests and human germline mutation rate. Science 295: 1037. [The Semipalatinsk study] Abstract