Evidence of radiation risk in childhood leukaemia

Ionising radiation has long been recognised as a cause of leukaemia in exposed children. But delegates at a conference in London yesterday heard how ground-breaking research is now providing evidence that the children of men exposed to radiation may also be at increased risk of developing leukaemia.

The causes of leukaemia in children are, in general, poorly understood. The disease is known to be multi-causal, and it is widely accepted that it is multi-stage, initiated in utero with some second event triggering development of the disease in childhood.

The incidence of childhood leukaemia in Britain increased dramatically during the twentieth century. The increase has mainly affected the under-five age group, in whom the risk increased by more than 50 per cent during the second half of the century alone. The reasons for the increase remain unclear and it is only by finding out more about the causes that we can establish whether it is possible to take preventive measures and halt the rising incidence. This is the motivation behind the conference – Childhood leukaemia: incidence, causal mechanisms and prevention – which is being hosted by CHILDREN with LEUKAEMIA, Britain’s leading charity devoted to the conquest of the disease.

The link between ionising radiation and childhood leukaemia is well-established. Increased rates of childhood leukaemia were found in those exposed at a young age to the atomic bombs in Japan. And those receiving radiation in utero from maternal X-rays have also been shown to be at higher risk of developing leukaemia. But it has only recently been recognised that ionising radiation not only increases mutation rates in the exposed somatic cells but also results in an elevated mutation rate many cell divisions after the initial irradiation damage.

Yuri Dubrova, Professor of Genetics at the University of Leicester, obtained the first experimental evidence that germ-line mutation rates in unexposed offspring of irradiated male mice do not return to the mutation rates seen in unexposed individuals but are maintained at levels similar to those of directly exposed males. He then went on to show that the elevated mutation rates persisted into the second generation of offspring, through both the male and female germ-lines.

Dubrova and his colleagues developed a novel, effective method for monitoring radiation-induced mutation in humans and studied germ-line mutation among families from rural areas of Ukraine and Belarus, both of which were heavily contaminated by fallout from the Chernobyl accident. They found a statistically significant 1.6-fold increase in mutation rate in the germ-line of exposed fathers. The maternal germ-line mutation rate was not elevated.

Commenting on the results of this study, Dubrova said "Experimental evidence for radiation-induced mutation in the human germ-line remains highly controversial. But our studies in Ukraine and Belarus have shown that genomic instability can be induced in the paternal germ-line in humans. It remains to be seen whether this instability can be transmitted to further generations, as has shown to be the case in our mouse studies."

Dubrova will be discussing the potential implications of his results for the estimates of genetic risk for humans. During the week long conference, there will be many presentations of new data as well as fresh reviews of older data. Both pre-conceptual and in utero exposure will come under scrutiny today, with factors such as cigarette smoke, electromagnetic fields and use of medication being presented for discussion.

It is hoped that out of the conference – which has attracted top international experts from Europe, America, Asia and Australia - will be born an agenda for future research. CHILDREN with LEUKAEMIA will be launching a £1m fund to support research in priority areas.