THERE is something baffling about how radiation kills cells. Much of the damage to DNA is caused by low-energy electrons, but no one could work out exactly how, as they are simply too feeble to tear off an atom, or even knock out another electron. Now the puzzle has been solved, and the result should aid the design of more effective radiotherapy.
Electromagnetic radiation or high-energy particles do their damage by breaking the helical backbone of a cell鈥檚 DNA, knocking out electrons in the process. Less energetic electrons, especially those with energies of less than 20 electronvolts, were once thought to be harmless. But two years ago L茅one Sanche and his team at the University of Sherbrooke in Quebec, Canada, caused a storm when they reported that these particles cause a large number of breaks in one or both strands of DNA (Science, vol 287, p 1658).
To investigate further, Tilmann M盲rk and his colleagues from the University of Innsbruck in Austria and the Claude Bernard University in Lyon, France, made a gas of uracil molecules 鈥� one of the bases that is attached to the backbone of RNA 鈥� and pumped low-energy electrons through it. They now report that negatively charged uracil ions emerged from the cloud (Physical Review Letters, vol 90, p 118,104).
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That was the vital clue. The researchers conclude that even electrons that do not have enough energy to damage the uracil molecule directly can disrupt it when they are absorbed into its ring-like structure. The extra negative charge is distributed round the ring, which expels a hydrogen atom (see Graphic), leaving behind a negatively charged uracil 鈥渞adical ion鈥�.
If the uracil were attached to an RNA chain, this could be enough to break the strand, M盲rk thinks. Even electrons with energies of less than 3 electronvolts, below the limit tested by Sanche鈥檚 team, can do this, and the same effect is likely to occur in DNA bases too, he says. He is planning more experiments to test the idea.
Sanche agrees that the mechanism is likely to be involved inside cells, adding that he now has preliminary data suggesting that DNA can also be damaged by electrons at ultra-low energies. 鈥淭his means there could be much more radiation damage by low-energy electrons than anticipated,鈥� he says.
The work should help researchers find drugs to make tumours more susceptible to radiotherapy. Cancerous cells already have an impaired ability to repair DNA damage, so they die more quickly than healthy cells when exposed to radiation. Researchers have found that injecting tumours with the related compound bromo-uracil makes the cells more susceptible to radiation. They knew that bromo-uracil is incorporated into the tumour鈥檚 DNA by replacing the base thymine, but they couldn鈥檛 work out why this made the DNA more likely to be damaged.
Now M盲rk and his colleagues have shown that ultra-low-energy electrons attack bromo-uracil more easily than uracil itself. They hope the discovery will enable them to find molecules that weaken the DNA even more effectively.