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EVEN the great-grandchildren of people exposed to radiation could inherit unstable genomes, a new study suggests. This instability may be the cause of the leukaemia cluster around Britain鈥檚 Sellafield nuclear plant.

Studies over the past few years have shown radiation damage to be surprisingly persistent. It increases mutation rates not just in cells directly zapped by radiation, but also in descendant cells many divisions later. Birth defects are more common in the offspring of mice exposed to radiation, and in the following generation too. Mutation rates are also high in both generations (Nature, vol 405, p 37).

Now geneticists have shown that even the fourth generation is affected. A team at the University of Leicester led by Yuri Dubrova took 20 male mice from three different strains and irradiated them either with high-energy neutrons for just over 2 hours, or a blast of X-rays for 2 or 4 minutes. They were then mated with healthy females from the same strain, and the offspring were allowed to breed with healthy animals to produce great-grandchildren of the original mice.

The team measured mutation rates in the mice by looking at two stretches of DNA called short tandem repeats, which are prone to spontaneous and radiation-induced mutations. They found mutation rates for the male and female offspring and in the following two generations were as high as in their irradiated ancestor, regardless of the type of radiation, the dose or the mouse strain.

The results also suggest that the radiation damage destabilises the entire genome of later generations, not just the sections damaged in the irradiated animal. 鈥淭here鈥檚 something global happening that鈥檚 affecting the stability of the whole genome,鈥� says Ruth Barber, a member of the Leicester team.

She thinks this stems from changes that don鈥檛 alter the genetic code but can still pass to a cell鈥檚 descendants. But no one knows what changes would cause the genome to become prone to mutations.

Whatever the mechanism, the results highlight the potential dangers facing the children of people exposed to radiation. The team says its results provide 鈥渁 plausible explanation for the apparent leukaemia cluster near Sellafield鈥�.

Childhood leukaemia is around 10 times as common in Seascale in Cumbria, where many Sellafield workers live, as in Britain overall. However, epidemiological studies have not conclusively linked this to the parents鈥� exposure. And Barber stresses that it鈥檚 not proven that the unstable DNA causes disease in mice, let alone people.

Studies of people who survived the atomic bomb blasts in Hiroshima and Nagasaki have found no mutations above background levels, says Richard Setlow, a biophysicist at Brookhaven National Laboratory in New York state. But now their children are under the spotlight. 鈥淚f anything is found, we鈥檒l want to go to the next generation,鈥� says Setlow. 鈥淲e need to find out how rapidly these mutations disappear鈥攐r get worse.鈥�